Erosive hand osteoarthritis and sarcopenia: data from Osteoarthritis Initiative cohort.

OBJECTIVES: There is no evidence linking specific osteoarthritis (OA) types, such as erosive hand OA (EHOA), with distant generalised changes in muscle composition (sarcopenia), which can potentially be modified. This study pioneers the exploration of the association between EHOA and sarcopenia, both of which are predominantly observed in the older adults. METHODS: Using the Osteoarthritis Initiative cohort, we selected hand OA (modified Kellgren and Lawrence (grade ≥2 in ≥1 hand joint) participants with radiographic central erosions in ≥1 joints (EHOA group) and propensity score-matched hand OA participants with no erosion (non-EHOA group). MRI biomarkers of thigh muscles were measured at baseline, year 2 and year 4 using a validated deep-learning algorithm. To adjust for 'local' effects of coexisting knee OA (KOA), participants were further stratified according to presence of radiographic KOA. The outcomes were the differences between EHOA and non-EHOA groups in the 4-year rate of change for both intramuscular adipose tissue (intra-MAT) deposition and contractile (non-fat) area of thigh muscles. RESULTS: After adjusting for potential confounders, 844 thighs were included (211 EHOA:633 non-EHOA; 67.1±7.5 years, female/male:2.9). Multilevel mixed-effect regression models showed that EHOA is associated a different 4-year rate of change in intra-MAT deposition (estimate, 95% CI: 71.5 mm2/4 years, 27.9 to 115.1) and contractile area (estimate, 95% CI: -1.8%/4 years, -2.6 to -1.0) of the Quadriceps. Stratified analyses showed that EHOA presence is associated with adverse changes in thigh muscle quality only in participants without KOA. CONCLUSIONS: EHOA is associated with longitudinal worsening of thigh muscle composition only in participants without concomitant KOA. Further research is needed to understand the systemic factors linking EHOA and sarcopenia, which unlike EHOA is modifiable through specific interventions.

Thigh muscle composition changes in knee osteoarthritis patients during weight loss: Sex-specific analysis using data from osteoarthritis initiative.

OBJECTIVES: Sex of patients with knee osteoarthritis (KOA) may impact changes in thigh muscle composition during weight loss, the most well-known disease-modifying intervention. We investigated longitudinal sex-based changes in thigh muscle quality during weight loss in participants with KOA. METHODS: Using Osteoarthritis Initiative (OAI) cohort data, we included females and males with baseline radiographic KOA who experienced > 5 % reduction in Body Mass Index (BMI) over four years. Using a previously validated deep-learning algorithm, we measured Magnetic Resonance Imaging (MRI)-derived biomarkers of thigh muscles at baseline and year-4. Outcomes were the intra- and inter-muscular adipose tissue (Intra-MAT and Inter-MAT) and contractile percentage of thigh muscles between females and males. The analysis adjusted for potential confounders, such as demographics, risk factors, BMI change, physical activity, diet, and KOA status. RESULTS: A retrospective selection of available thigh MRIs from KOA participants who also had a 4-year weight loss (>5 % of BMI) yielded a sample comprising 313 thighs (192 females and 121 males). Female and male participants exhibited a comparable degree of weight loss (females: -9.72 ± 4.38, males: -8.83 ± 3.64, P-value=0.060). However, the changes in thigh muscle quality were less beneficial for females compared to males, as shown by a less degree of longitudinal decrease in Intra-MAT (change difference,95 %CI: 783.44 mm2/4-year, 505.70 to 1061.19, P-value<0.001) and longitudinal increase in contractile percentage (change difference,95 %CI: -3.9 %/4-year, -6.5 to -1.4, P-value=0.019). CONCLUSIONS: In participants with KOA and 4-year weight loss, the longitudinal changes in thigh muscle quality were overall beneficial but to a less degree in females compared to males. Further research is warranted to investigate the underlying mechanisms and develop sex-specific interventions to optimize muscle quality during weight loss.

Statin use and longitudinal changes in quantitative MRI-based biomarkers of thigh muscle quality: data from Osteoarthritis Initiative.

OBJECTIVE: To assess whether changes in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis. METHODS: This retrospective cohort study used data from the Osteoarthritis Initiative study. Statin users and non-users were matched for relevant covariates using 1:1 propensity-score matching. Participants were further stratified according to baseline radiographic knee osteoarthritis status. We used a validated deep-learning method for thigh muscle MRI segmentation and calculation of muscle quality biomarkers at baseline, 2nd, and 4th visits. Mean difference and 95% confidence intervals (CI) in longitudinal 4-year measurements of muscle quality biomarkers, including cross-sectional area, intramuscular adipose tissue, contractile percent, and knee extensors and flexors maximum and specific contractile force (force/muscle area) were the outcomes of interest. RESULTS: After matching, 3772 thighs of 1910 participants were included (1886 thighs of statin-users: 1886 of non-users; age: 62 ± 9 years (average ± standard deviation), range: 45-79; female/male: 1). During 4 years, statin use was associated with a slight decrease in muscle quality, indicated by decreased knee extension maximum (mean-difference, 95% CI: - 1.85 N/year, - 3.23 to - 0.47) and specific contractile force (- 0.04 N/cm2/year, - 0.07 to - 0.01), decreased thigh muscle contractile percent (- 0.03%/year, - 0.06 to - 0.01), and increased thigh intramuscular adipose tissue (3.06 mm2/year, 0.53 to 5.59). Stratified analyses showed decreased muscle quality only in participants without/at-risk of knee osteoarthritis but not those with established knee osteoarthritis. CONCLUSIONS: Statin use is associated with a slight decrease in MRI-based measures of thigh muscle quality over 4 years. However, considering statins' substantial cardiovascular benefits, these slight muscle changes may be relatively less important in overall patient care.

Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study.

OBJECTIVES: We examined the association between diabetes mellitus (DM) and longitudinal MRI biomarkers for thigh muscle degeneration in patients with knee osteoarthritis (KOA) and their mediatory role in worsening KOA-related symptoms. METHODS: The Osteoarthritis Initiative (OAI) participants with radiographic KOA (Kellgren-Lawrence grade ≥ 2) were included. Thighs and corresponding knees of KOA patients with versus without self-reported DM were matched for potential confounders using propensity score (PS) matching. We developed and used a validated deep learning method for longitudinal thigh segmentation. We assessed the association of DM with 4-year longitudinal muscle degeneration in biomarkers of muscle cross-sectional area (CSA) and contractile percentage (non-fat CSA/total CSA). We further investigated whether DM is associated with 9-year risk of KOA radiographic progression, knee replacement (KR), and symptoms worsening. Finally, we evaluated whether the DM-KOA worsening association is mediated through preceding muscle degeneration. RESULTS: After PS matching, 698 thighs/knees were included (185:513 with:without DM; average ± SD age:64 ± 8-years; female/male:1.4). Baseline DM was associated with a decreased contractile percent of total thigh muscles and quadriceps (mean difference, 95%CI -0.16%/year, -0.25 to -0.07, and -0.21%/year, -0.33 to -0.08). DM was also associated with an increased risk of worsening KOA-related symptoms (hazard ratio, 95%CI 1.70, 1.18-2.46) but not radiographic progression or KR. The decrease in quadriceps contractile percent partially mediated the increased risk of symptoms worsening in patients with DM. CONCLUSIONS: Baseline DM is associated with thigh muscle degeneration and KOA-related symptoms worsening. As a potentially modifiable risk factor, DM-associated longitudinal thigh muscle degeneration may partially mediate the symptoms worsening in patients with DM and coexisting KOA. KEY POINTS: • Diabetes mellitus (DM) is associated with worsening knee osteoarthritis (KOA)-related symptoms. • As a potentially modifiable factor, DM-associated thigh muscle (quadriceps) degeneration partially mediates the worsening of KOA-related symptoms.

Role of Thigh Muscle Changes in Knee Osteoarthritis Outcomes: Osteoarthritis Initiative Data.

Background Longitudinal data on the association of quantitative thigh muscle MRI markers with knee osteoarthritis (KOA) outcomes are scarce. These associations are of clinical importance, with potential use for thigh muscle-directed disease-modifying interventions. Purpose To measure KOA-associated longitudinal changes in MRI-derived muscle cross-sectional area (CSA) and adipose tissue and their association with downstream symptom worsening and knee replacement (KR). Materials and Methods In a secondary analysis of the Osteoarthritis Initiative multicenter prospective cohort (February 2004 through October 2015), knees of participants with available good-quality thigh MRI scans at baseline and at least one follow-up visit were included and classified as with and without KOA according to baseline radiographic Kellgren-Lawrence grade of 2 or higher and matched for confounders with use of propensity score matching. An automated deep learning model for thigh MRI two-dimensional segmentation was developed and tested. Markers of muscle CSA and intramuscular adipose tissue (intra-MAT) were measured at baseline and 2nd- and 4th-year follow-up (period 1) and compared between knees with and without KOA by using linear mixed-effect regression models. Furthermore, in knees with KOA, the association of period 1 changes in muscle markers with risk of KR (Cox proportional hazards) and symptom worsening (mixed-effect models) during the 4th to 9th year (period 2) was evaluated. Results This study included 4634 matched thighs (2317 with and 2317 without KOA) of 2344 participants (mean age, 62 years ± 9 [SD]; 1292 women). Compared with those without, knees with KOA had a decrease in quadriceps CSA (mean difference, -8.21 mm2/year; P = .004) and an increase in quadriceps intra-MAT (1.98 mm2/year; P = .007). Decreased CSA and increased intra-MAT of quadriceps during period 1 was predictive of downstream (period 2) KOA symptom worsening (Western Ontario and McMaster Universities Osteoarthritis Index total score: odds ratio, 0.24 [negative association] [P < .001] and 1.38 [P = .012], respectively). Quadriceps CSA changes were negatively associated with higher future KR risk (hazard ratio, 0.70; P < .001). Conclusion Knee osteoarthritis was associated with longitudinal MRI-derived decreased quadriceps cross-sectional area and increased intramuscular adipose tissue. These potentially modifiable risk factors were predictive of downstream symptom worsening and knee replacement. Clinical trial registration no. NCT00080171 © RSNA, 2022 Online supplemental material is available for this article.

Statin use and MRI subchondral bone marrow lesion worsening in generalized osteoarthritis: longitudinal analysis from Osteoarthritis Initiative data.

OBJECTIVES: To determine the association between statin therapy and knee MRI-detected subchondral bone marrow lesion (BML) longitudinal worsening in patients with Heberden's nodes (HNs) as the hallmark of generalized osteoarthritis (OA) phenotype. METHODS: All participants gave informed consent, and IRB approved HIPAA-compliant protocol. We assessed the worsening in BML volume and number of affected subregions in the Osteoarthritis Initiative (OAI) participants with HNs at baseline clinical examination (HN+), using the semi-quantitative MRI Osteoarthritis Knee Scores at baseline and 24 months. Participants were classified according to baseline BML involvement as "no/minimal" (≤ 2/14 knee subregions affected and maximum BML score ≤ 1) or "moderate/severe." Statin users and non-users were selected using 1:1 propensity-score (PS) matching for OA and cardiovascular disease (CVD)-related potential confounding variables. We assessed the association between statin use and increasing BML score and affected subregions using adjusted mixed-effect regression models. RESULTS: The PS-matched HN+ participants (63% female, aged 63.5 ± 8.5-year-old) with no/minimal and moderate/severe BML cohorts consisted of 332 (166:166, statin users: non-users) and 380 (190:190) knees, respectively. In the HN+ participants with no/minimal BML, statin use was associated with lower odds of both BML score worsening (odds ratio, 95% confidence interval: 0.62, 0.39-0.98) and increased number of affected subregions (0.54, 0.33-0.88). There was no such association in HN- participants or those HN+ participants with baseline moderate/severe BML. CONCLUSION: In patients with CVD indications for statin therapy and generalized OA phenotype (HN+), statin use may be protective against the OA-related subchondral bone damage only in the subgroup of participants with no/minimal baseline BML. KEY POINTS: • Statin use may reduce the risk of subchondral bone damage in specific osteoarthritis patients with a generalized phenotype, minimal subchondral bone damage, and cardiovascular statin indications.

Kneeling as a risk factor of patellofemoral joint cartilage damage worsening: an exploratory analysis on the Osteoarthritis Initiative.

OBJECTIVES: To determine whether kneeling activity is associated with the MRI measures of patellofemoral (PF) joint cartilage damage worsening in subjects with/without patella alta (PA). METHODS: Baseline and 24-month 3-T MR images and semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) of PF joint of 600 subjects from the FNIH study, a nested study within the Osteoarthritis Initiative (OAI), were extracted. At baseline visit, subjects were asked how many days per week they participated in kneeling activities lasted ≥ 30 min. Insall-Salvati ratio (ISR) (patellar tendon/patellar height) was measured on baseline MRIs by a musculoskeletal radiologist; ISR ≥ 1.3 was considered PA. Regression analysis adjusted for confounding variables was used to assess the impact of kneeling on worsening of MOAKS cartilage over 24 months. The potential moderating effect of PA was evaluated using adjusted regression analysis. RESULTS: Six hundred subjects (58.8% female, years, BMI = 30.7 ± 4.8 kg/m2) were included; 13.7%, 6.2%, and 5.5% of participants reported 1 day, 2-5 days, and ≥ 6 days of kneeling activities per week. A higher frequency of kneeling activity was associated with the increased risk of MOAKS cartilage score worsening (adjusted OR (95% CI): 2.33 (1.08-5.06)). Stratification analysis showed that only ≥ 6 days/week of kneeling activities was associated with the worsening of MOAKS cartilage scores (2.74 (1.03-7.27)). When we included the presence of PA in regression models, the OR (95% CI) for the association between kneeling and PF cartilage damage will decrease to 1.26 (0.78-2.04), suggesting the potential role of PA as the moderator variable. CONCLUSION: Extensive kneeling activity (≥ 6 days/week) may be associated with the MRI-based worsening of PF cartilage damage, specifically in subjects with an underlying patella alta. KEY POINTS: • Frequent daily kneeling activity is associated with a higher risk of patellofemoral cartilage damage resulting in patellofemoral osteoarthritis. • The cartilage damage associated with extensive kneeling activity may be worse in subjects with an underlying patella alta (i.e., high-riding patella).

Distinct patterns of hippocampal subfield volume loss in left and right mesial temporal lobe epilepsy.

OBJECTIVE: To investigate the pattern and severity of hippocampal subfield volume loss in patients with left and right mesial temporal lobe epilepsy (mTLE) using quantitative MRI volumetric analysis. METHODS: A total of 21 left and 14 right mTLE subjects, as well as 15 healthy controls, were enrolled in this cross-sectional study. A publically available magnetic resonance imaging (MRI) brain volumetry system (volBrain) was used for volumetric analysis of hippocampal subfields. The T1-weighted images were processed with a HIPS pipeline. RESULTS: A distinct pattern of hippocampal subfield atrophy was found between left and right mTLE patients when compared with controls. Patients with left mTLE exhibited ipsilateral hippocampal atrophy and segmental volume depletion of the Cornu Ammonis (CA) 2/CA3, CA4/dentate gyrus (DG), and strata radiatum-lacunosum-moleculare (SR-SL-SM). Those with right mTLE exhibited similar ipsilateral hippocampal atrophy but with additional segmental CA1 volume depletion. More extensive bilateral subfield volume loss was apparent with right mTLE patients. CONCLUSION: We demonstrate that left and right mTLE patients show a dissimilar pattern of hippocampal subfield atrophy, suggesting the pathophysiology of epileptogenesis in left and right mTLE to be different.

The level and trend of road traffic injuries attributable mortality rate in Iran, 1990-2015: a story of successful regulations and a roadmap to design future policies.

BACKGROUND: Road-Traffic-Injuries (RTIs) are predicted to rise up to the fifth leading cause of worldwide death by 2030 and Iran has the third highest RTIs mortality among higher-middle income countries. Although the high mortality of RTI in Iran is a warning, it provides the opportunity to indirectly assess the implemented RTI-related regulations' effectiveness via high-resolution relevant statistics and, hence, Iran could serve as a guide for countries with similar context. In order to do so, we utilized this study to report the time and spatial trends of RTIs-related mortality in different age and sex groups and road user classes in Iran. METHODS: Based on the national death-registration-system (DRS), cemeteries data, and the demographic characteristics, and after addressing incompleteness, we estimated mortality rates using spatiotemporal and Gaussian process regression models. We assessed Pearson seatbelt and helmet use and RTIs-attributable Age-Standardized-Morality-Rate (ASMR) associations. We also predicted RTIs-death-numbers, 2012-2020, by fitting a Generalized Additive Model to assess the status of achieving relevant sustainable development goal (SDG), namely reducing the number of RTIs-related deaths by half. RESULTS: Overall RTIs-attributable death and ASMR at the national level increased from 12.64 [95% UI, 9.52-16.86] to 29.1 [22.76-37.14] per 100,000 people in the time period of 1990-2015. The trend consisted of an increasing segment in 1990-2003 followed by a decreasing part till 2015. The highest percentage of death belonged to the three-or-more-wheels motorized vehicles. Pedestrian injuries percentage increased significantly and the highest mortality rate occurred in 85 years and older individuals. Low prevalence of seatbelt and helmet use were observed in provinces with higher than the median ASMR due to the relevant cause of each. RTIs-attributable death number is expected to reduce by 15.99% till 2020 which is lower than the established SDG goal. CONCLUSIONS: Despite the observed substantial moderation in the RTI-ASMR, Iran is till among the leading countries in terms of the highest mortality rates in the world. The enforced regulations including speed limitations (particularly for elder pedestrians) and mandatory use of seatbelt and helmet (for young adult and male drivers) had a considerable effect on ASMR, nevertheless, the RTI burden reduction needs to be sustained and enhanced.

Gray matter volume and estimated brain age gap are not linked with sleep-disordered breathing.

Alzheimer's disease (AD) and sleep-disordered breathing (SDB) are prevalent conditions with a rising burden. It is suggested that SDB may contribute to cognitive decline and advanced aging. Here, we assessed the link between self-reported SDB and gray matter volume in patients with AD, mild cognitive impairment (MCI) and healthy controls (HCs). We further investigated whether SDB was associated with advanced brain aging. We included a total of 330 participants, divided based on self-reported history of SDB, and matched across diagnoses for age, sex and presence of the Apolipoprotein E4 allele, from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Gray-matter volume was measured using voxel-wise morphometry and group differences in terms of SDB, cognitive status, and their interaction were assessed. Further, using an age-prediction model fitted on gray-matter data of external datasets, we predicted study participants' age from their structural images. Cognitive decline and advanced age were associated with lower gray matter volume in various regions, particularly in the bilateral temporal lobes. Brains age was well predicted from the morphological data in HCs and, as expected, elevated in MCI and particularly in AD subjects. However, there was neither a significant difference between regional gray matter volume in any diagnostic group related to the SDB status, nor in SDB-by-cognitive status interaction. Moreover, we found no difference in estimated chronological age gap related to SDB, or by-cognitive status interaction. Contrary to our hypothesis, we were not able to find a general or a diagnostic-dependent association of SDB with either gray-matter volumetric or brain aging.

Insight into blood pressure targets for universal coverage of hypertension services in Iran: the 2017 ACC/AHA versus JNC 8 hypertension guidelines.

BACKGROUND: We compared the prevalence, awareness, treatment, and control of hypertension in Iran based on two hypertension guidelines; the 2017 ACC/AHA -with an aggressive blood pressure target of 130/80 mmHg- and the commonly used JNC8 guideline cut-off of 140/90 mmHg. We shed light on the implications of the 2017 ACC/AHA for population subgroups and high-risk individuals who were eligible for non-pharmacologic and pharmacologic therapies. METHODS: Data was obtained from the Iran national STEPS 2016 study. Participants included 27,738 adults aged ≥25 years as a representative sample of Iranians. Regression models of survey design were used to examine the determinants of prevalence, awareness, treatment, and control of hypertension. RESULTS: The prevalence of hypertension based on JNC8 was 29.9% (95% CI: 29.2-30.6), which soared to 53.7% (52.9-54.4) based on the 2017 ACC/AHA. The percentage of awareness, treatment, and control were 59.2% (58.0-60.3), 80.2% (78.9-81.4), and 39.1% (37.4-40.7) based on JNC8, which dropped to 37.1% (36.2-38.0), 71.3% (69.9-72.7), and 19.6% (18.3-21.0), respectively, by applying the 2017 ACC/AHA. Based on the new guideline, adults aged 25-34 years had the largest increase in prevalence (from 7.3 to 30.7%). They also had the lowest awareness and treatment rate, contrary to the highest control rate (36.5%) between age groups. Compared with JNC8, based on the 2017 ACC/AHA, 24, 15, 17, and 11% more individuals with dyslipidaemia, high triglycerides, diabetes, and cardiovascular disease events, respectively, fell into the hypertensive category. Yet, based on the 2017 ACC/AHA, 68.2% of individuals falling into the hypertensive category were eligible for receiving pharmacologic therapy (versus 95.7% in JNC8). LDL cholesterol< 130 mg/dL, sufficient physical activity (Metabolic Equivalents≥600/week), and Body Mass Index were found to change blood pressure by - 3.56(- 4.38, - 2.74), - 2.04(- 2.58, - 1.50), and 0.48(0.42, 0.53) mmHg, respectively. CONCLUSIONS: Switching from JNC8 to 2017 ACC/AHA sharply increased the prevalence and drastically decreased the awareness, treatment, and control in Iran. Based on the 2017 ACC/AHA, more young adults and those with chronic comorbidities fell into the hypertensive category; these individuals might benefit from earlier interventions such as lifestyle modifications. The low control rate among individuals receiving treatment warrants a critical review of hypertension services.

Statin Use and Knee Osteoarthritis Outcome Measures according to the Presence of Heberden Nodes: Results from the Osteoarthritis Initiative.

Background The exact contribution of statins to knee osteoarthritis (OA) radiographic outcomes and the characteristics of patients with OA as potential responders to statins remain unclear. Purpose To evaluate the effect of statin use on the incidence of radiographic knee OA (development of Kellgren-Lawrence grade ≥2) and progression of joint space narrowing (JSN) according to the nodal OA status defined according to the presence of Heberden nodes (HNs). Materials and Methods Institutional review boards approved this HIPAA-compliant protocol, and all participants gave informed consent. The Osteoarthritis Initiative (OAI) cohort, which began in 2004 and is ongoing (https://clinicaltrials.gov identifier, NCT00080171), was used to conduct a longitudinal 1:1 propensity score-matched retrospective analysis of prospectively collected data. Participants were classified as having HN-positive or HN-negative findings according to the presence of HNs at baseline physical examination. In each cohort, per-protocol and new-user design were used to match statin initiators (participants who reported ≤1 year of statin use before enrollment) and nonusers (participants who reported no statin use before enrollment) for variables that potentially contributed to confounding by indication bias. Participants were followed up annually over 8 years. Any associations between statin use and longitudinal knee OA radiographic incidence, JSN progression, or nonacceptable symptomatic state incidence was assessed by using hazard ratios (HRs) of Cox regression. Results In the longitudinal analysis, there were 832 knees of 602 participants (pair-matched knees of statin initiators and nonusers) in the HN-positive cohort (mean age, 64.7 years ± 8.0 [standard deviation]; 377 patients were female [62.6%]) and 386 knees of 285 participants in the HN-negative cohort (mean age, 58.9 years ± 8.2; 144 patients were female [50.5%]). In the HN-positive cohort, statin users had 46% lower risk of JSN progression in comparison with matched nonusers (HR, 0.54; 95% confidence interval [CI]: 0.36, 0.93; P = .02). In contrast, in the HN-negative cohort, statin use had no association with radiographic JSN progression (HR, 1.37; [95% CI: 0.74, 2.53]; P = .32). Conclusion Statin use was associated with reduced risk of radiographic knee osteoarthritis joint space narrowing progression in patients with nodal osteoarthritis. © RSNA, 2019 Online supplemental material is available for this article.

Global, regional and national burden of testicular cancer, 1990-2016: results from the Global Burden of Disease Study 2016.

OBJECTIVE: To provide estimates of the global incidence, mortality and disability-adjusted life-years (DALYs) associated with testicular cancer (TCa) between 1990 and 2016, using findings from the Global Burden of Disease (GBD) 2016 study. MATERIALS AND METHODS: For the GBD 2016 study, cancer registry data and a vital registration system were used to estimate TCa mortality. Mortality to incidence ratios were used to transform mortality estimates to incidence, and to estimate survival, which was then used to estimate 10-year prevalence. Prevalence was weighted using disability weights to estimate years lived with disability (YLDs). Age-specific mortality and a reference life expectancy were used to estimate years of life lost (YLLs). DALYs are the sum of YLDs and YLLs. RESULTS: Global incidence of TCa showed a 1.80-fold increase from 37 231 (95% uncertainty interval [ UI] 36 116-38 515) in 1990 to 66 833 (95% UI 64 487-69 736) new cases in 2016. The age-standardized incidence rate also increased from 1.5 (95% UI 1.45-1.55) to 1.75 (95% UI 1.69-1.83) cases per 100 000. Deaths from TCa remained stable between 1990 and 2016 [1990: 8394 (95% UI 7980-8904), 2016: 8651 (95% UI 8292-9027)]. The TCa age-standardized death rate decreased between 1990 and 2016, from 0.39 (95% UI 0.37-0.41) to 0.25 (95% UI 0.24-0.26) per 100 000; however, the decreasing trend was not similar in all regions. Global TCa DALYs decreased by 2% and reached 391 816 (95% UI 372 360-412 031) DALYs in 2016. The age-standardized DALY rate also decreased globally between 1990 and 2016 (10.31 [95% UI 9.82-10.84]) per 100 000 in 2016). CONCLUSION: Although the mortality rate for TCa has decreased over recent decades, large disparities still exist in TCa mortality, probably as a result of lack of access to healthcare and oncological treatment. Timely diagnosis of this cancer, by improving general awareness, should be prioritized. In addition, improving access to effective therapies and trained healthcare workforces in developing and under-developed areas could be the next milestones.

Physical activity profile of the Iranian population: STEPS survey, 2016.

BACKGROUND: Insufficient physical activity (IPA) is one of the leading causes of premature mortality through the increased burden of non-communicable diseases. From 1990 to 2017, the percentage of low physical activity attributable disability-adjusted life years (DALY) increased globally by 1.5 times and 2-fold in Iran, causing more than 1.2 million deaths worldwide and 18,000 deaths in Iran in 2017. Reports suggest that Iran, a developing middle-income country, suffers from a high level of IPA. Socioeconomic and cultural alterations along with the country's developments expose the population to IPA risk. We aimed to describe IPA prevalence in Iran's adult population, categorized by demographics, geographical region, and activity domains to assess the present pattern of physical inactivity and its domains in the country. METHODS: In 2016, in order to represent Iran's adult population, adult participants (n: 30541) from 30 provinces were selected using systematic proportional to size cluster sampling. Physical activity (PA) was assessed via the Global Physical Activity Questionnaire, calculating the Metabolic Equivalent of Task (MET) value in minutes per week for work, recreation, and transport domains. Insufficient physical activity (IPA) was defined according to WHO's recommendation (less than 600 METs per week). Adjusted odds ratios of IPA associates for sociodemographic, lifestyle related variables, and metabolic risk factors were reported. RESULTS: A high prevalence of IPA was seen in the total population (54.7%, 95%CI: 54.0-55.3) with a considerable difference between the two genders (males: 45.3% (95%CI: 44.3-46.3); females: 61.9% (95%CI: 61.0-62.7)). Work-related activity was the domain with the greatest percentage of total PA, whereas, both genders lacked recreational activities. In our findings, being female, a housekeeper, younger and living in urban areas were significantly associated with higher levels of IPA. Moreover, insufficient fruit and vegetable consumption, lack of alcohol consumption, having a personal vehicle, and finally, having a medical history of diabetes were significantly associated with the presence of IPA in our population. Among the study population, 33.6% (95%CI: 33.0-34.2) had at least 4 h of sedentary behavior in a typical day. CONCLUSIONS: Widespread IPA among the Iranian adult population is of major concern. In our findings, we observed a considerable gap in the prevalence and pattern of IPA between the two genders. Additionally, IPA was associated with living in urban areas, unhealthy lifestyle habits and a history of other metabolic risk factors. Thus, a prompt initiative for population-specific actions should be taken.

Diagnostic Performance of Three-dimensional MRI for Depicting Cartilage Defects in the Knee: A Meta-Analysis.

Purpose To determine the diagnostic performance of three-dimensional (3D) MRI for the depiction and characterization of cartilage defects within the knee joint by using arthroscopy and/or open surgery as the standard of reference. Materials and Methods A systematic literature search was performed to extract diagnostic studies published between January 1985 and October 2017. Two independent investigators assessed the methodologic quality of each study by using Quality Assessment of Diagnostic Accuracy Studies 2. Bivariate random-effects model was used to compare the diagnostic odds ratio (DOR) of 3D and two-dimensional (2D) MRI for helping to detect knee cartilage defects and to assess the effect of relevant covariates on diagnostic performance of 3D MRI. Meta-regression analysis was performed to assess DOR of 3D MRI during the last 3 decades. Results Twenty-seven studies (composed of 1710 MRI examinations) were included. Of those, 16 (59%) studies compared the diagnostic performance of 3D and 2D MRI. The diagnostic performance of 3D MRI statistically significantly improved over the last 3 decades (P = .003). Three-dimensional MRI obtained by using 3.0-T field strength had higher DOR relative to 1.5-T or lower field strength (relative DOR, 4.05; P = .01). Three-dimensional multiplanar reformation was associated with higher specificity (P = .001) compared with conventional axial, sagittal, and coronal 2D MRI planes. Three-dimensional fast-spin-echo sequences provided higher sensitivity and specificity (P < .05) than did 2D MRI. Conclusion Three-dimensional MRI currently provides comparable diagnostic performance to two-dimensional MRI, with improvement in diagnostic performance achieved by using 3.0-T field strength, three-dimensional fast-spin-echo sequences, and multiplanar reformation. © RSNA, 2018 Online supplemental material is available for this article.

Relationship between cerebrospinal fluid biomarkers and structural brain network properties in Parkinson's disease.

BACKGROUND: Pathological accumulation of α-synuclein, amyloid-ß42 , and tau proteins in the brain is considered critical for development of various neurodegenerative diseases. OBJECTIVES: We investigated the association between CSF levels of these biomarkers, brain structural connectivity, and the UPDRS in PD. METHODS: Diffusion tensor images and CSF biomarkers (α-synuclein, amyloid-ß42 , total tau, and phosphorylated tau181) from 132 drug-naïve, nondemented PD patients and 61 healthy controls were obtained from the Parkinson's Progression Markers Initiative database. After network reconstruction of structural connectivity patterns, global interconnectivity measures (including global efficiency, clustering coefficient, and characteristic path length) and local efficiency were calculated. Network properties and CSF biomarkers were compared between PD patients and healthy controls. The association of CSF biomarkers with network properties and UPDRS-III score was investigated. RESULTS: Global measures (but not local efficiency) and CSF α-synuclein were significantly lower in PD patients. Global efficiency and clustering coefficient correlated positively with α-synuclein, Aß42 , and total tau CSF levels. Furthermore, these CSF biomarkers showed no significant association with the UPDRS-III score. CONCLUSIONS: This study examined the association of CSF biomarkers that reflect the brain pathology, with structural brain connectivity and UPDRS-III in PD. Our results revealed an association between the abnormal aggregation of α-synuclein, Aß42 , and tau proteins and structural connectivity disruption in PD patients. In summary, a combination of structural imaging and measurement of CSF biomarkers provide a better understanding of the pathogenesis of PD. © 2018 International Parkinson and Movement Disorder Society.

Imaging Genomics and Multiomics: A Guide for Beginners Starting Radiomics-Based Research.

Radiomics uses advanced mathematical analysis of pixel-level information from radiologic images to extract existing information in traditional imaging algorithms. It is intended to find imaging biomarkers related to the genomics of tumors or disease patterns that improve medical care by advanced detection of tumor response patterns in tumors and to assess prognosis. Radiomics expands the paradigm of medical imaging to help with diagnosis, management of diseases and prognostication, leveraging image features by extracting information that can be used as imaging biomarkers to predict prognosis and response to treatment. Radiogenomics is an emerging area in radiomics that investigates the association between imaging characteristics and gene expression profiles. There are an increasing number of research publications using different radiomics approaches without a clear consensus on which method works best. We aim to describe the workflow of radiomics along with a guide of what to expect when starting a radiomics-based research project.

Validation of the self-reported diagnosis of diabetes mellitus, hypercholesterolemia, and hypertension in Iran; STEPS 2016.

Purpose: As a part of STEPwise approach to risk factor Surveillance (STEPS) study, our aim was to evaluate the validity of the self-reported diagnosis of diabetes (DM), hypertension (HTN), and hypercholesterolemia (Hyper-Chol) in the Iranian population. Methods: Using systematic proportional to size cluster sampling, 27,232 participants were included in our study. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to assess the validity of self-reported diagnoses. Furthermore, logistic regression was employed to examine the relationship between the validity of self-reported diagnoses and sociodemographic and lifestyle factors. All analyses were performed using STATA version 14. Results: The PPV for self-report of DM, HTN, and Hyper-Chol were estimated to be 69%, 74% and 80%, and NPV measured up to 95%, 84%, and 50%, respectively. Positive/negative self-reports were more accurate among older (younger) individuals. Age had a negative correlation with the validity of self-reported Hyper-Chol but a positive correlation with the validity of self-reported DM and hypertension HTN. Additionally, an increase in BMI was associated with an increase/decrease in PPV and a decrease/increase in NPV across all diseases. Conclusion: Self-report studies hold value in situations where direct in-person interaction is not feasible, either due to prohibitive costs or restrictions imposed by infectious diseases (COVID-19). Self-report surveys are valuable tools in studying the epidemiology of diseases; however, the type of the disease, the study purpose, either finding sick people or healthy people, the age subgroups, and socioeconomic status should be taken into consideration.

Cachexia in preclinical rheumatoid arthritis: Longitudinal observational study of thigh magnetic resonance imaging from osteoarthritis initiative cohort.

BACKGROUND: Preclinical rheumatoid arthritis (Pre-RA) is defined as the early stage before the development of clinical RA. While cachexia is a well-known and potentially modifiable complication of RA, it is not known if such an association exists also in the Pre-RA stage. To investigate such issue, we aimed to compare the longitudinal alterations in the muscle composition and adiposity of participants with Pre-RA with the matched controls. METHODS: In this observational cohort study, the Osteoarthritis Initiative (OAI) participants were categorized into Pre-RA and propensity score (PS)-matched control groups. Pre-RA was retrospectively defined as the absence of RA from baseline to year-2, with progression to physician-diagnosed clinical RA between years 3-8 of the follow-up period. Using a validated deep learning algorithm, we measured MRI biomarkers of thigh muscles and adiposity at baseline and year-2 follow-ups of the cohort. The outcomes were the differences between Pre-RA and control groups in the 2-year rate of change for thigh muscle composition [cross-sectional area (CSA) and intramuscular adipose tissue (Intra-MAT)] and adiposity [intermuscular adipose tissue (Inter-MAT) and subcutaneous adipose tissue (SAT)]. Linear mixed-effect regression models were used for comparison. RESULTS: After 1:3 PS-matching of the groups for confounding variables (demographics, risk factors, co-morbidities, and knee osteoarthritis status), 408 thighs (102 Pre-RA and 306 control) of 322 participants were included (age mean ± SD: 61.7 ± 8.9 years; female/male: 1.8). Over a 2-year period, Pre-RA was associated with a larger decrease in total thigh muscle CSA [estimate, 95% confidence interval (CI): -180.13 mm2/2-year, -252.80 to -107.47, P-value < 0.001]. Further examination of thigh muscle composition showed that the association of the presence of Pre-RA with a larger decrease in muscle CSA over 2 years was noticeable in the quadriceps, flexors, and sartorius muscle groups (P-values < 0.05). Comparison of changes in total adipose tissue showed no difference between Pre-RA and control participants (estimate, 95% CI: 48.48 mm2/2-year, -213.51 to 310.47, P-value = 0.691). However, in the detailed analysis of thigh adiposity, Pre-RA presence was associated with a larger increase in Inter-MAT (estimate, 95% CI: 150.55 mm2/2-year, 95.58 to 205.51, P-value < 0.001). CONCLUSIONS: Preclinical rheumatoid arthritis is associated with a decrease in muscle cross-sectional area and an increase in intermuscular adipose tissue, similar to rheumatoid cachexia in clinical rheumatoid arthritis. These findings suggest the presence of cachexia in the preclinical phase of rheumatoid arthritis. Given that cachexia, which can exacerbate health outcomes, is potentially modifiable, this study emphasizes the importance of early identification of patients in their preclinical phase.

Levothyroxine use and longitudinal changes in thigh muscles in at-risk participants for knee osteoarthritis: preliminary analysis from Osteoarthritis Initiative cohort.

BACKGROUND: We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence. METHODS: Using the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th year and were matched with levothyroxine non-users for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes. RESULTS: We included 1043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male: 4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: - 16.06 mm2/year, - 26.70 to - 5.41) but not thigh muscles' composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15-2.75) and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19-3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use. CONCLUSIONS: Our exploratory analyses suggest that levothyroxine use may be associated with loss of quadriceps muscle mass, which may also partially mediate the increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier. Therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes in the thigh muscles.