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ObjectiveTo determine the association of varus thrust during walking to incident and worsening medial tibiofemoral cartilage damage and bone marrow lesions (BMLs) over 2 years in older adults with or at risk for osteoarthritis (OA).MethodSubjects from the Multicenter Osteoarthritis Study (MOST) were studied. Varus thrust was visually assessed from high-speed videos of forward walking trials. Baseline and two-year MRIs were acquired from one knee per subject and read for cartilage loss and BMLs. Logistic regression with generalized estimating equations was used to estimate the odds of incident and worsening cartilage loss and BMLs, adjusting for age, sex, race, body mass index (BMI), and clinic site. The analysis was repeated stratified by varus, neutral, and valgus alignment.Results1007 participants contributed one knee each. Varus thrust was observed in 29.9% of knees. Knees with thrust had 2.17 [95% CI: 1.51, 3.11] times the odds of incident medial BML, 2.51 [1.85, 3.40] times the odds of worsening medial BML, and 1.85 [1.35, 2.55] times the odds of worsening medial cartilage loss. When stratified by alignment, varus knees also had significantly increased odds of these outcomes.ConclusionVarus thrust observed during walking is associated with increased odds of incident and worsening medial BMLs and worsening medial cartilage loss. Increased odds of these outcomes persist in varus-aligned knees.

PurposeTo explore the association of baseline trabecular bone structure with incident tibiofemoral (TF) osteoarthritis (OA) and with increase in joint space narrowing (JSN) score.MethodsThe Multicenter Osteoarthritis Study (MOST) includes subjects with or at risk for knee OA. Knee radiographs were scored for Kellgren-Lawrence (KL) grade and JSN at baseline, 30, 60 and 84 months. Knees (KL ≤ 1) at baseline were assessed for incident OA (KL ≥ 2) and increases in JSN score. For each knee image at baseline, a variance orientation transform method (VOT) was applied to subchondral tibial bone regions of medial and lateral compartments. Seventeen fractal parameters were calculated per region. Associations of each parameter with OA incidence and with medial and lateral JSN increases were explored using logistic regression. Analyses were stratified by digitized film (DF) vs computer radiography (CR) and adjusted for confounders.ResultsOf 894 knees with CR and 1158 knees with DF, 195 (22%) and 303 (26%) developed incident OA. Higher medial bone roughness was associated with increased odds of OA incidence at 60 and 84 months and also, medial and lateral JSN increases (primarily vertical). Lower medial and lateral anisotropy was associated with increased odds of medial and lateral JSN increase. Compared to DF, CR had more associations and also, similar results at overlapping scales.ConclusionBaseline trabecular bone texture was associated with incident radiographic OA and increase of JSN scores independently of risk factors for knee OA. Higher roughness and lower anisotropy were associated with increased odds for radiographic OA change.

PurposeTo determine if asymmetry between hips in pain or radiographic osteoarthritis (RHOA) is associated with worse pain and joint space narrowing (JSN) at baseline and longitudinally in knees contralateral to more affected hips.MethodsWe studied 279 participants in the Osteoarthritis Initiative with baseline asymmetry between hips in pain and 483 with asymmetry in RHOA none of whom had a hip replacement for ≥4 years after baseline. RHOA assessed from pelvis radiographs was categorized as none, possible or definite and hip pain on most days of a month in the past year as present/absent. Knee pain (WOMAC scale) and JSN (fixed flexion radiographs) were categorized as none, mild and moderate-severe. We compared knees contralateral and ipsilateral to more affected hips on baseline knee pain and JSN using clustered multinomial regression and on change in knee pain and JSN over 4-5 years using generalized linear and logistic estimating equations.ResultsKnees contralateral to painful hips had less baseline pain ("moderate-severe" vs "none", relative risk ratio [RRR]: 0.39, 95% CI = 0.27-0.57), but greater baseline JSN ("moderate-severe" vs "none", RRR: 1.62, 95% CI = 1.09-2.38) and greater worsening of pain during follow-up (P = 0.001). Knees contralateral to hips with worse RHOA had nonsignificant trends for greater baseline JSN (P = 0.10) and JSN progression (P = 0.17).ConclusionThese findings provide limited support for the hypothesis that early asymmetry in hip pain and RHOA is associated with worse pain and structural outcomes in knees contralateral to the more affected hip.

BackgroundPrevious studies suggest that the antioxidants vitamins C and E may protect against development of knee osteoarthritis (OA). We examined the association of circulating levels of vitamin C and E with incident whole knee radiographic OA (WKROA).MethodsWe performed a nested case-control study of incident WKROA in MOST, a cohort of 3,026 men and women aged 50-79 years with, or at high risk of, knee OA. Incident cases were knees without either tibiofemoral (TF) or patellofemoral (PF) OA at baseline that developed TF and/or PF OA by 30-month follow-up. Two control knees per case were selected from those eligible for WKROA that did not develop it. Vitamin C and E (alpha-tocopherol) assays were done on baseline supernatant plasma (PCA) and serum samples, respectively. We examined the association of gender-specific tertiles of vitamin C and E with incident WKROA using logistic regression with GEE, adjusting for age, gender, and obesity.ResultsSubjects without WKROA at baseline who were in the highest tertile of vitamin C had a higher incidence of WKROA [adjusted OR = 2.20 (95% CI: 1.12-4.33); P-value = 0.021], with similar results for the highest tertile of vitamin E [adjusted OR = 1.89 (1.02-3.50); P-value = 0.042], compared to those in the lowest tertiles. P-values for the trend of vitamin C and E tertiles and incident WKROA were 0.019 and 0.030, respectively.ConclusionsHigher levels of circulating vitamin C and E did not provide protection against incident radiographic knee OA, and may be associated with an increased risk of knee OA.

OBJECTIVE: Vascular calcification holds promise as a useful cardiovascular risk maker. Our objective was to examine the association between breast vascular calcification and risk of cardiovascular disease (CVD) outcomes. METHODS: A cohort study was performed among 12,761 women, 40-79 years of age at baseline (1968-1973), who attended multiphasic health checkups that included mammography. The outcome measures included coronary heart disease (CHD), ischemic stroke, transient ischemic attack (TIA), hemorrhagic stroke, and heart failure, ascertained using discharge diagnosis codes and death records through December 31, 2000 (median follow-up, 24.8 years). RESULTS: Breast vascular calcification was present in 424 (3%) women. It was independently and positively associated with age, high parity, and diabetes and inversely associated with education level and current cigarette smoking. After adjustment for age, education level, race, cigarette smoking, alcohol use, body mass index (BMI), serum total cholesterol, hypertension, diabetes, parental history of myocardial infarction (MI), parity, and hormone replacement therapy (HRT), breast vascular calcification was associated with a 1.32-fold increased risk of CHD (95% confidence interval [CI] 1.08-1.60), a 1.41-fold increased risk of ischemic stroke (95% CI 1.11-1.78), and a 1.52-fold increased risk of heart failure (95% CI 1.18-1.98). CONCLUSIONS: Breast vascular calcification detected as part of a screening mammogram was an independent risk factor for multiple cardiovascular outcomes among women. The value of mammography in cardiovascular risk stratification deserves further investigation. [ABSTRACT FROM AUTHOR]

Social capital has been shown to be associated with reduced mortality due to cardiovascular disease. Our aim was to determine the association of time-varying community-level social capital (CSC) with recurrence of acute coronary syndrome using a retrospective cohort study design. A total of 34,752 men and women were identified, aged 30-85 years, who were hospitalized for acute coronary syndrome between January 1, 1998 and December 31, 2002 in Kaiser Permanente Northern California, USA, an integrated health care delivery system. The primary outcome was recurrent non-fatal or fatal acute coronary syndrome; median follow-up was 19 months. We estimated random-effects, three-level Cox proportional hazard models adjusting for sex, age, race/ethnicity, comorbidities, medication use, and revascularization procedures at level 1, median household income for the census block-group at level 2, and income inequality, racial/ethnic concentration, penetration of health maintenance organizations, and CSC at level 3. Our measure of CSC was the previously validated Petris Social Capital Index (PSCI). We found that a one-standard deviation increase in the PSCI, after adjusting for the above covariates, was significantly associated with decreased recurrence of acute coronary syndrome only for those living in areas where block-group level median household income was below the grand median compared to those living in areas where block-group level median household income was at the grand median or above. These results suggest that community-level social capital may be negatively associated with recurrence of acute coronary syndrome among lower-income individuals. [ABSTRACT FROM AUTHOR]

Background: Adherence to the American Cancer Society (ACS) guidelines of avoiding obesity, maintaining physical activity, and consuming a diet rich in fruits, vegetables, and whole grains is associated with longer survival in colorectal cancer (CRC) survivors. Dietary components of the ACS guidelines may act in part by changing the microbiome, which is implicated in CRC outcomes., Objectives: We conducted a pilot cross-sectional study to explore associations between ACS guidelines and the gut microbiome., Methods: Stool samples and questionnaires were collected from 28 CRC survivors at the University of California, San Francisco from 2019 to 2020. ACS scores were calculated based on validated questionnaires. Gut microbial community structure from 16S amplicons and gene/pathway abundances from metagenomics were tested for associations with the ACS score and its components using ANOVA and general linear models., Results: The overall ACS score was not significantly associated with variations in the fecal microbiota. However, fruit and vegetable intake and alcohol intake accounted for 19% (P = 0.005) and 13% (P = 0.01) of variation in the microbiota, respectively. Fruit/vegetable consumption was associated with increased microbial diversity, increased Firmicutes, decreased Bacteroidota, and changes to multiple genes and metabolic pathways, including enriched pathways for amino acid and short-chain fatty acid biosynthesis and plant-associated sugar degradation. In contrast, alcohol consumption was positively associated with overall microbial diversity, negatively associated with Bacteroidota abundance, and associated with changes to multiple genes and metabolic pathways. The other components of the ACS score were not statistically significantly associated with the fecal microbiota in our sample., Conclusions: These results guide future studies examining the impact of changes in the intake of fruits, vegetables, and alcoholic drinks on the gut microbiome of CRC survivors., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

A myriad of organ-specific complications have been observed with COVID-19. While racial/ethnic minorities have been disproportionately burdened by this disease, our understanding of the unique risk factors for complications among a diverse population of cancer patients remains limited. This is a multi-institutional, multi-ethnic cohort study evaluating COVID-19 complications among cancer patients. Patients with an invasive cancer diagnosis and confirmed SARS-CoV-2 infection were identified from March to November 2020. Demographic and clinical data were obtained and a multivariate logistic regression was employed to evaluate the impact of demographic and clinical factors on COVID-19 complications. The study endpoints were evaluated independently and included any complication, sepsis, pulmonary complications and cardiac complications. A total of 303 patients were evaluated, of whom 48% were male, 79% had solid tumors, and 42% were Hispanic/Latinx (Hispanic). Malignant hematologic cancers were associated with a higher risk of sepsis (OR 3.93 (95% CI 1.58-9.81)). Male patients had a higher risk of sepsis (OR 4.42 (95% CI 1.63-11.96)) and cardiac complications (OR 2.02 (95% CI 1.05-3.89)). Hispanic patients had a higher odds of any complication (OR 2.31 (95% CI 1.18-4.51)) and other race was associated with a higher odds of cardiac complications (OR 2.41 (95% CI 1.01-5.73)). Clinically, fever, cough, and ≥2 co-morbidities were independently significantly associated with any complication. This analysis evaluated covariates that can significantly predict a myriad of complications among a multi-ethnic cohort of cancer patients. The conclusions drawn from this analysis elucidate a mechanistic understanding of differential illness severity from COVID-19., (© 2022. The Author(s).)

Objective: The lack of strong association between knee osteoarthritis (OA) structural features and pain continues to perplex researchers and clinicians. Evaluating the patellofemoral joint in addition to the tibiofemoral joint alone has contributed to explaining this structure-pain discordance, hence justifying a more comprehensive evaluation of whole-knee OA and pain. The present study, therefore, was undertaken to evaluate the association between patellofemoral and tibiofemoral OA features with localized anterior knee pain (AKP) using 2 study designs., Methods: Using cross-sectional data from the Multicenter Osteoarthritis Study, our first approach was a within-person, knee-matched design in which we identified participants with unilateral AKP. We then assessed magnetic resonance imaging (MRI)-derived OA features (cartilage damage, bone marrow lesions [BMLs], osteophytes, and inflammation) in both knees and evaluated the association of patellofemoral and tibiofemoral OA features to unilateral AKP. In our second approach, MRIs from 1 knee per person were scored, and we evaluated the association of OA features to AKP in participants with AKP and participants with no frequent knee pain., Results: Using the first approach (n = 71, 66% women, mean ± SD age 69 ± 8 years), lateral patellofemoral osteophytes (odds ratio [OR] 5.0 [95% confidence interval (95% CI) 1.7-14.6]), whole-knee joint effusion-synovitis (OR 4.7 [95% CI 1.3-16.2]), and infrapatellar synovitis (OR 2.8 [95% CI 1.0-7.8]) were associated with AKP. Using the second approach (n = 882, 59% women, mean ± SD age 69 ± 7 years), lateral and medial patellofemoral cartilage damage (prevalence ratio [PR] 2.3 [95% CI 1.3-4.0] and PR 1.9 [95% CI 1.1-3.3], respectively) and lateral patellofemoral BMLs (PR 2.6 [95% CI 1.5-4.7]) were associated with AKP., Conclusion: Patellofemoral but not tibiofemoral joint OA features and inflammation were associated with AKP., (© 2021 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: The risks associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated illness, coronavirus disease 2019 (COVID-19), among patients with a cancer diagnosis have not been fully characterized. This study leverages data from a multi-institutional cohort study, the University of California Cancer COVID Consortium, to evaluate outcomes associated with SARS-CoV-2 infection among patients with cancer., Methods: Clinical data were collected from March to November 2020 and included patient demographics, cancer history and treatment, SARS-CoV-2 exposure and testing, and COVID-19 clinical management and outcomes. Multivariate ordinal logistic regression permitting unequal slopes was used to evaluate the impact of demographic, disease, and treatment factors on SARS-CoV-2 related hospitalization, intensive care unit (ICU) admission, and mortality., Findings: Among all evaluated patients (n = 303), 147 (48%) were male, 118 (29%) were older adults (≥65 years old), and 104 (34%) were non-Hispanic white. A subset (n = 63, 21%) had hematologic malignancies and the remaining had solid tumors. Patients were hospitalized for acute care (n = 79, 26%), ICU-level care (n = 28, 9%), or died (n = 21, 7%) due to COVID-19. Patients with ≥2 comorbidities were more likely to require acute care (odds ratio [OR] 2.09 [95% confidence interval (CI), 1.23-3.55]). Cough was identified as a significant predictor of ICU hospitalization (OR 2.16 [95% CI, 1.03-4.57]). Importantly, mortality was associated with an active cancer diagnosis (OR 3.64 [95% CI, 1.40-9.5]) or advanced age (OR 3.86 [95% CI, 1.2-12.44])., Interpretation: This study observed that patients with active cancer or advanced age are at an increased risk of death from COVID-19. These study observations can inform risk counseling related to COVID-19 for patients with a cancer diagnosis., (© The Author(s) 2022. Published by Oxford University Press.)

Objective: To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes., Methods: We used longitudinal data from the Multicenter Osteoarthritis Study, a community-based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes., Results: Among the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16-3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87-5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit., Conclusion: Subchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To determine reliability among four experienced and calibrated readers in cross-sectional and longitudinal semi-quantitative MRI assessments of knee osteoarthritis (OA) in the Multicenter Osteoarthritis (MOST) study., Design: From all MOST participants with at least one knee with readable 60-month and 84-month paired knee MRIs (1.0 ​T extremity systems), we selected 10 subjects having a spectrum of baseline disease severity of cartilage, bone marrow lesions, and meniscal damage and a spectrum of longitudinal changes in severity at 24 months follow-up. MRIs were independently assessed using the WORMS grading system by four musculoskeletal radiologists with the chronological sequence known to the readers. Kappa statistics were used to determine agreement between each pair of readers and Kendall's coefficient of concordance to determine average agreement across readers., Results: For most features, cross-sectional reliability was substantial to almost perfect. Regarding longitudinal reliability (detection of longitudinal change), inter-reader reliability as weighted kappa values ranged from 0.62 to 0.78 for cartilage damage, 0.75-0.88 for bone marrow lesions, 0.75-0.92 for meniscal tears, 0.67-0.95 for meniscal extrusion, 0.51-0.77 for bone attrition, 0.43-0.76 for osteophytes, 0.31-0.70 for Hoffa-synovitis, and 0.47-0.85 for effusion-synovitis. Kendall's coefficient ranged from 0.65 to 0.98., Conclusion: High levels of cross-sectional reliability and moderate to high longitudinal reliability was achieved using four experienced readers in semiquantitative MRI-assessment of most knee OA features., Competing Interests: Michel D. Crema, Frank W. Roemer, and Monica D. Marra are stockholders of Boston Imaging Core Lab (BICL), LLC. Ali Guermazi is president of BICL, LLC. He is also a consultant for MerckSerono, Pfizer, TissueGene, Roche, Galapagos, and AstraZeneca. There is no conflict of interest for the remaining authors.

Background: Postpartum women are at increased risk for lower limb musculoskeletal disorders. Foot arch collapse following pregnancy has been reported as a mechanism for this increased risk. However, dynamic changes during gait in postpartum women have not been reported. Therefore, we assessed the association between parity and dynamic foot pronation during gait., Objective: To determine (1) if there is an association between parity and dynamic foot pronation (center of pressure excursion index, CPEI) during gait; and (2) the extent to which there is a dose-effect of parity on foot pronation., Design: The Multicenter Osteoarthritis Study (MOST) Study is a longitudinal cohort study of adults with or at risk for knee osteoarthritis (OA)., Setting: Two communities in the United States, Birmingham, Alabama and Iowa City, Iowa., Interventions: Not applicable PARTICIPANTS: A population-based sample of 1177 MOST participants who were female, had complete CPEI and parity data and completed the baseline, 30- and 60-month visits., Main Outcome Measures: Odds of a one quintile decrease in CPEI by parity group and mean CPEI by parity group., Results: In 1177 women, mean age was 67.7 years and mean body mass index (BMI) was 30.6 kg/m 2 . As parity increased, there was significantly greater foot pronation, lower mean CPEI: 19.1 (18.2-20.1), 18.9 (18.4-19.4), 18 (17.5-18.6) to 17.5 (16.4-18.6) in the 0 to 4 and >5 children groups, respectively; (P = .002), which remained significant after adjusting for race and clinic site (P = .005). There was a positive linear trend (β = 1.08, 1.03-1.14) in odds ratios of a one quintile decrease in CPEI (greater pronation) with increasing parity level (P = .004), which remained significant after adjusting for race and clinic site (P = .01). After adjusting for age and BMI, these two associations were no longer statistically significant., Conclusions: This study indicates a positive correlation between parity and greater dynamic pronation of the feet., (© 2020 American Academy of Physical Medicine and Rehabilitation.)

Objective: To identify plasma markers associated with an increased risk of radiographic knee osteoarthritis(OA) progression using a metabolomics approach., Methods: Study participants were from the Multicenter Osteoarthritis Study (MOST) and were categorized into 2 groups based on the presence of baseline radiographic OA. Subjects in group 1 had unilateral knee OA and subjects in group 2 had bilateral knee OA. Progression was defined as a half-grade or greater worsening in joint space width at 30-month follow-up. For group 1, a participant progressed when their OA knee showed radiographic progression and the contralateral knee developed OA; for group 2, a participant progressed when both knees with OA showed radiographic progression. Metabolomic profiling was performed on plasma samples collected at baseline and logistic regression was performed to test the association between each metabolite and knee OA progression after adjustment for age, sex, BMI, and clinic site. Significance was defined as P ≤ 0.0003 in the combined analysis., Results: There were 234 progressors (57 in group 1 and 177 in group 2) and 322 nonprogressors (206 in group 1 and 116 in group 2) included in the analyses. Among 157 metabolites studied, we found that odds of progression were 1.46 times higher per SD increase of phenylalanine level (95% CI 1.20-1.77, P = 0.0001) in the combined analysis. Sex-specific analysis showed that an association was seen in women ( P = 0.0002) but not in men., Conclusion: Our data suggest that phenylalanine might be a novel plasma marker for higher risk of bilateral radiographic knee OA progression in women.

Objective: Patellofemoral (PF) alignment and trochlear morphology are associated with PF osteoarthritis (OA) and knee pain, but whether they are associated with localized anterior knee pain is unknown, which is believed to be a symptom specific to PF joint pathology. We therefore aimed to evaluate the relation of PF alignment and morphology, as well as PFOA and tibiofemoral OA, to anterior knee pain., Methods: The Multicenter Osteoarthritis Study is a cohort study of individuals with, or at risk for, knee OA. We evaluated cross-sectional associations of PF alignment, trochlear morphology, and PF and tibiofemoral radiographic OA, with localized anterior knee pain (defined with a pain map). We used 2 approaches: a within-person knee-matched evaluation of participants with unilateral anterior knee pain (conditional logistic regression), and a cohort approach comparing those with anterior knee pain to those without (binomial regression)., Results: With the within-person knee-matched approach (n = 110; 64% women, mean age 70 years, body mass index [BMI] 30.9), PF alignment, morphology, and tibiofemoral OA were not associated with unilateral anterior knee pain. Radiographic PFOA was associated with pain, odds ratio 5.3 (95% confidence interval [95% CI] 1.6-18.3). Using the cohort approach (n = 1,818; 7% of knees with anterior knee pain, 59% women, mean age 68 years, BMI 30.4), results were similar: only PFOA was associated with pain, with a prevalence ratio of 2.2 (95% CI 1.4-3.4)., Conclusion: PF alignment and trochlear morphology were not associated with anterior knee pain in individuals with, or at risk for, knee OA. Radiographic PFOA, however, was associated with pain, suggesting that features of OA, more so than mechanical features, may contribute to localized symptoms., (© 2019, American College of Rheumatology.)