Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer.

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.

Are Current Survival Prediction Tools Useful When Treating Subsequent Skeletal-related Events From Bone Metastases?

BACKGROUND: Bone metastasis in advanced cancer is challenging because of pain, functional issues, and reduced life expectancy. Treatment planning is complex, with consideration of factors such as location, symptoms, and prognosis. Prognostic models help guide treatment choices, with Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) showing promise in predicting survival for initial spinal metastases and extremity metastases treated with surgery or radiotherapy. Improved therapies extend patient lifespans, increasing the risk of subsequent skeletal-related events (SREs). Patients experiencing subsequent SREs often suffer from disease progression, indicating a deteriorating condition. For these patients, a thorough evaluation, including accurate survival prediction, is essential to determine the most appropriate treatment and avoid aggressive surgical treatment for patients with a poor survival likelihood. Patients experiencing subsequent SREs often suffer from disease progression, indicating a deteriorating condition. However, some variables in the SORG prediction model, such as tumor histology, visceral metastasis, and previous systemic therapies, might remain consistent between initial and subsequent SREs. Given the prognostic difference between patients with and without a subsequent SRE, the efficacy of established prognostic models-originally designed for individuals with an initial SRE-in addressing a subsequent SRE remains uncertain. Therefore, it is crucial to verify the model's utility for subsequent SREs. QUESTION/PURPOSE: We aimed to evaluate the reliability of the SORG-MLAs for survival prediction in patients undergoing surgery or radiotherapy for a subsequent SRE for whom both the initial and subsequent SREs occurred in the spine or extremities. METHODS: We retrospectively included 738 patients who were 20 years or older who received surgery or radiotherapy for initial and subsequent SREs at a tertiary referral center and local hospital in Taiwan between 2010 and 2019. We excluded 74 patients whose initial SRE was in the spine and in whom the subsequent SRE occurred in the extremities and 37 patients whose initial SRE was in the extremities and the subsequent SRE was in the spine. The rationale was that different SORG-MLAs were exclusively designed for patients who had an initial spine metastasis and those who had an initial extremity metastasis, irrespective of whether they experienced metastatic events in other areas (for example, a patient experiencing an extremity SRE before his or her spinal SRE would also be regarded as a candidate for an initial spinal SRE). Because these patients were already validated in previous studies, we excluded them in case we overestimated our result. Five patients with malignant primary bone tumors and 38 patients in whom the metastasis's origin could not be identified were excluded, leaving 584 patients for analysis. The 584 included patients were categorized into two subgroups based on the location of initial and subsequent SREs: the spine group (68% [399]) and extremity group (32% [185]). No patients were lost to follow-up. Patient data at the time they presented with a subsequent SRE were collected, and survival predictions at this timepoint were calculated using the SORG-MLAs. Multiple imputation with the Missforest technique was conducted five times to impute the missing proportions of each predictor. The effectiveness of SORG-MLAs was gauged through several statistical measures, including discrimination (measured by the area under the receiver operating characteristic curve [AUC]), calibration, overall performance (Brier score), and decision curve analysis. Discrimination refers to the model's ability to differentiate between those with the event and those without the event. An AUC ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An AUC of 0.7 is considered clinically acceptable discrimination. Calibration is the comparison between the frequency of observed events and the predicted probabilities. In an ideal calibration, the observed and predicted survival rates should be congruent. The logarithm of observed-to-expected survival ratio [log(O:E)] offers insight into the model's overall calibration by considering the total number of observed (O) and expected (E) events. The Brier score measures the mean squared difference between the predicted probability of possible outcomes for each individual and the observed outcomes, ranging from 0 to 1, with 0 indicating perfect overall performance and 1 indicating the worst performance. Moreover, the prevalence of the outcome should be considered, so a null-model Brier score was also calculated by assigning a probability equal to the prevalence of the outcome (in this case, the actual survival rate) to each patient. The benefit of the prediction model is determined by comparing its Brier score with that of the null model. If a prediction model's Brier score is lower than the null model's Brier score, the prediction model is deemed as having good performance. A decision curve analysis was performed for models to evaluate the "net benefit," which weighs the true positive rate over the false positive rate against the "threshold probabilities," the ratio of risk over benefit after an intervention was derived based on a comprehensive clinical evaluation and a well-discussed shared-decision process. A good predictive model should yield a higher net benefit than default strategies (treating all patients and treating no patients) across a range of threshold probabilities. RESULTS: For the spine group, the algorithms displayed acceptable AUC results (median AUCs of 0.69 to 0.72) for 42-day, 90-day, and 1-year survival predictions after treatment for a subsequent SRE. In contrast, the extremity group showed median AUCs ranging from 0.65 to 0.73 for the corresponding survival periods. All Brier scores were lower than those of their null model, indicating the SORG-MLAs' good overall performances for both cohorts. The SORG-MLAs yielded a net benefit for both cohorts; however, they overestimated 1-year survival probabilities in patients with a subsequent SRE in the spine, with a median log(O:E) of -0.60 (95% confidence interval -0.77 to -0.42). CONCLUSION: The SORG-MLAs maintain satisfactory discriminatory capacity and offer considerable net benefits through decision curve analysis, indicating their continued viability as prediction tools in this clinical context. However, the algorithms overestimate 1-year survival rates for patients with a subsequent SRE of the spine, warranting consideration of specific patient groups. Clinicians and surgeons should exercise caution when using the SORG-MLAs for survival prediction in these patients and remain aware of potential mispredictions when tailoring treatment plans, with a preference for less invasive treatments. Ultimately, this study emphasizes the importance of enhancing prognostic algorithms and developing innovative tools for patients with subsequent SREs as the life expectancy in patients with bone metastases continues to improve and healthcare providers will encounter these patients more often in daily practice. LEVEL OF EVIDENCE: Level III, prognostic study.

Machine Learning Radiomics Signature for Differentiating Lymphoma versus Benign Splenomegaly on CT.

BACKGROUND: We aimed to develop and validate a preoperative CT-based radiomics signature for differentiating lymphoma versus benign splenomegaly. METHODS: We retrospectively analyzed CT studies from 139 patients (age range 26-93 years, 43% female) between 2011 and 2019 with histopathological diagnosis of the spleen (19 lymphoma, 120 benign) and divided them into developing (n = 79) and testing (n = 60) datasets. The volumetric radiomic features were extracted from manual segmentation of the whole spleen on venous-phase CT imaging using PyRadiomics package. LASSO regression was applied for feature selection and development of the radiomic signature, which was interrogated with the complete blood cell count and differential count. All p values < 0.05 were considered to be significant. RESULTS: Seven features were selected for constructing the radiomic signature after feature selection, including first-order statistics (10th percentile and Robust Mean Absolute Deviation), shape-based (Surface Area), and texture features (Correlation, MCC, Small Area Low Gray-level Emphasis and Low Gray-level Zone Emphasis). The radiomic signature achieved an excellent diagnostic accuracy of 97%, sensitivity of 89%, and specificity of 98%, distinguishing lymphoma versus benign splenomegaly in the testing dataset. The radiomic signature significantly correlated with the platelet and segmented neutrophil percentage. CONCLUSIONS: CT-based radiomics signature can be useful in distinguishing lymphoma versus benign splenomegaly and can reflect the changes in underlying blood profiles.

Do the American guideline-based leisure time physical activity levels for civilians benefit the mental health of military personnel?

Backgrounds: This study aimed to clarify the association of American guideline-based leisure time physical activity (PA) level with mental health in 4,080 military personnel in Taiwan. Methods: The moderate intensity PA level was assessed according to the total running time per week (wk) reported in a self-administered questionnaire over the previous 6 months and was categorized into PA level <150, 150-299, and ≥300 min/wk. Mental stress was assessed by the Brief Symptom Rating Scale (BSRS)-5 for which ≥15 points were classified as great mental stress. Suicide ideation (SI) was graded as 1 for mild, 2 for moderate, and 3 or 4 for severe. Multivariable logistic regression analysis was employed to determine the association between PA and mental health while adjusting for demographics, smoking, alcohol intake, betel nut chewing, and obesity. Results: As compared to participants with a PA level of <150 min/wk., those with PA levels 150-299 min/wk. and ≥ 300 min/wk. had a lower possibility of SI ≥1 [odds ratios (ORs) and 95% confidence intervals (CIs): 0.58 (0.40-0.83) and 0.23 (0.14-0.36), respectively] and SI ≥1 and/or BSRS-5 ≥ 15 [ORs: 0.55 (0.39-0.79) and 0.21 (0.13-0.34), respectively]. The possibilities were more significantly lower for SI ≥2 [ORs: 0.37 (0.20-0.68) and 0.10 (0.04-0.26), respectively] and SI ≥2 and/or BSRS-5 ≥ 15 [ORs: 0.35 (0.20-0.62) and 0.10 (0.04-0.25), respectively]. Conclusion: Our findings indicate that participating in moderate-intensity leisure time PA level for ≥150 min/wk. may have a positive effect on mental health among military personnel. The impact appears to be even more significant when engaging in a higher PA level of ≥300 min/wk.

Comparing Magnetic Resonance Fingerprinting (MRF) and the MAGiC Sequence for Simultaneous T1 and T2 Quantitative Measurements in the Female Pelvis: A Prospective Study.

The aim of this study was to explore the potential of magnetic resonance fingerprinting (MRF), an emerging quantitative MRI technique, in measuring relaxation values of female pelvic tissues compared to the conventional magnetic resonance image compilation (MAGiC) sequence. The study included 32 female patients who underwent routine pelvic MRI exams using anterior and posterior array coils on a 3T clinical scanner. Our findings demonstrated significant correlations between MRF and MAGiC measured T1 and T2 values (p < 0.0001) for various pelvic tissues, including ilium, femoral head, gluteus, obturator, iliopsoas, erector spinae, uterus, cervix, and cutaneous fat. The tissue contrasts generated from conventional MRI and synthetic MRF also showed agreement in bone, muscle, and uterus for both T1-weighted and T2-weighted images. This study highlights the strengths of MRF in providing simultaneous T1 and T2 mapping. MRF offers distinct tissue contrast and has the potential for accurate diagnosis of female pelvic diseases, including tumors, fibroids, endometriosis, and pelvic inflammatory disease. Additionally, MRF shows promise in monitoring disease progression or treatment response. Overall, the study demonstrates the potential of MRF in the field of female pelvic organ imaging and suggests that it could be a valuable addition to the clinical practice of pelvic MRI exams. Further research is needed to establish the clinical utility of MRF and to develop standardized protocols for its implementation in clinical practice.

Does the Presence of Missing Data Affect the Performance of the SORG Machine-learning Algorithm for Patients With Spinal Metastasis? Development of an Internet Application Algorithm.

BACKGROUND: The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA) was developed to predict the survival of patients with spinal metastasis. The algorithm was successfully tested in five international institutions using 1101 patients from different continents. The incorporation of 18 prognostic factors strengthens its predictive ability but limits its clinical utility because some prognostic factors might not be clinically available when a clinician wishes to make a prediction. QUESTIONS/PURPOSES: We performed this study to (1) evaluate the SORG-MLA's performance with data and (2) develop an internet-based application to impute the missing data. METHODS: A total of 2768 patients were included in this study. The data of 617 patients who were treated surgically were intentionally erased, and the data of the other 2151 patients who were treated with radiotherapy and medical treatment were used to impute the artificially missing data. Compared with those who were treated nonsurgically, patients undergoing surgery were younger (median 59 years [IQR 51 to 67 years] versus median 62 years [IQR 53 to 71 years]) and had a higher proportion of patients with at least three spinal metastatic levels (77% [474 of 617] versus 72% [1547 of 2151]), more neurologic deficit (normal American Spinal Injury Association [E] 68% [301 of 443] versus 79% [1227 of 1561]), higher BMI (23 kg/m2 [IQR 20 to 25 kg/m2] versus 22 kg/m2 [IQR 20 to 25 kg/m2]), higher platelet count (240 × 103/µL [IQR 173 to 327 × 103/µL] versus 227 × 103/µL [IQR 165 to 302 × 103/µL], higher lymphocyte count (15 × 103/µL [IQR 9 to 21× 103/µL] versus 14 × 103/µL [IQR 8 to 21 × 103/µL]), lower serum creatinine level (0.7 mg/dL [IQR 0.6 to 0.9 mg/dL] versus 0.8 mg/dL [IQR 0.6 to 1.0 mg/dL]), less previous systemic therapy (19% [115 of 617] versus 24% [526 of 2151]), fewer Charlson comorbidities other than cancer (28% [170 of 617] versus 36% [770 of 2151]), and longer median survival. The two patient groups did not differ in other regards. These findings aligned with our institutional philosophy of selecting patients for surgical intervention based on their level of favorable prognostic factors such as BMI or lymphocyte counts and lower levels of unfavorable prognostic factors such as white blood cell counts or serum creatinine level, as well as the degree of spinal instability and severity of neurologic deficits. This approach aims to identify patients with better survival outcomes and prioritize their surgical intervention accordingly. Seven factors (serum albumin and alkaline phosphatase levels, international normalized ratio, lymphocyte and neutrophil counts, and the presence of visceral or brain metastases) were considered possible missing items based on five previous validation studies and clinical experience. Artificially missing data were imputed using the missForest imputation technique, which was previously applied and successfully tested to fit the SORG-MLA in validation studies. Discrimination, calibration, overall performance, and decision curve analysis were applied to evaluate the SORG-MLA's performance. The discrimination ability was measured with an area under the receiver operating characteristic curve. It ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An area under the curve of 0.7 is considered clinically acceptable discrimination. Calibration refers to the agreement between the predicted outcomes and actual outcomes. An ideal calibration model will yield predicted survival rates that are congruent with the observed survival rates. The Brier score measures the squared difference between the actual outcome and predicted probability, which captures calibration and discrimination ability simultaneously. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. A decision curve analysis was performed for the 6-week, 90-day, and 1-year prediction models to evaluate their net benefit across different threshold probabilities. Using the results from our analysis, we developed an internet-based application that facilitates real-time data imputation for clinical decision-making at the point of care. This tool allows healthcare professionals to efficiently and effectively address missing data, ensuring that patient care remains optimal at all times. RESULTS: Generally, the SORG-MLA demonstrated good discriminatory ability, with areas under the curve greater than 0.7 in most cases, and good overall performance, with up to 25% improvement in Brier scores in the presence of one to three missing items. The only exceptions were albumin level and lymphocyte count, because the SORG-MLA's performance was reduced when these two items were missing, indicating that the SORG-MLA might be unreliable without these values. The model tended to underestimate the patient survival rate. As the number of missing items increased, the model's discriminatory ability was progressively impaired, and a marked underestimation of patient survival rates was observed. Specifically, when three items were missing, the number of actual survivors was up to 1.3 times greater than the number of expected survivors, while only 10% discrepancy was observed when only one item was missing. When either two or three items were omitted, the decision curves exhibited substantial overlap, indicating a lack of consistent disparities in performance. This finding suggests that the SORG-MLA consistently generates accurate predictions, regardless of the two or three items that are omitted. We developed an internet application (https://sorg-spine-mets-missing-data-imputation.azurewebsites.net/) that allows the use of SORG-MLA with up to three missing items. CONCLUSION: The SORG-MLA generally performed well in the presence of one to three missing items, except for serum albumin level and lymphocyte count (which are essential for adequate predictions, even using our modified version of the SORG-MLA). We recommend that future studies should develop prediction models that allow for their use when there are missing data, or provide a means to impute those missing data, because some data are not available at the time a clinical decision must be made. CLINICAL RELEVANCE: The results suggested the algorithm could be helpful when a radiologic evaluation owing to a lengthy waiting period cannot be performed in time, especially in situations when an early operation could be beneficial. It could help orthopaedic surgeons to decide whether to intervene palliatively or extensively, even when the surgical indication is clear.

Effects of Intravascular Photobiomodulation on Insomnia, Muscle Soreness, and Biochemistry Profiles: An Eight-Year Retrospective Cohort.

BACKGROUND: Although cognitive-behavioral therapy is the first-line treatment for insomnia, pharmacotherapy is often prescribed to treat insomnia and related symptoms. In addition, muscle relaxants are commonly prescribed to alleviate muscle soreness when the pain is unbearable. However, pharmacotherapy can lead to numerous side effects. The non-drug strategy intravascular laser irradiation of blood (iPBM) has been advocated to improve pain, wound healing, blood circulation, and blood cell function to relieve insomnia and muscle soreness symptoms. Therefore, we assessed whether iPBM improves blood parameters and compared drug use before and after iPBM therapy. METHODS: Consecutive patients who received iPBM therapy between January 2013 and August 2021 were reviewed. The associations between laboratory data, pharmacotherapies, and iPBM therapy were retrospectively analyzed. We compared patient characteristics, blood parameters, and drug use within the three months before the first treatment and the three months after the last treatment. We also compared the changes before and after treatment in patients who received ≥10 or 1-9 iPBM treatments. RESULT: We assessed 183 eligible patients who received iPBM treatment. Of them, 18 patients reported insomnia disturbance, and 128 patients reported pain in any part of their body. After the treatment, HGB and HCT significantly increased after treatment in both the ≥10 and 1-9 iPBM treatment groups (HGB p < 0.001 and p = 0.046; HCT p < 0.001 and p = 0.029, respectively). Pharmacotherapy analysis revealed no significant differences in drug use before and after treatment, though drug use tended to decrease after iPBM. CONCLUSIONS: iPBM therapy is an efficient, beneficial, and feasible treatment that increases HGB and HCT. While the results of this study do not support the suggestion that iPBM reduces drug use, further larger studies using symptom scales are needed to confirm the changes in insomnia and muscle soreness after iPBM treatment.

A Machine Learning Algorithm for Predicting 6-Week Survival in Spinal Metastasis: An External Validation Study Using 2,768 Taiwanese Patients.

INTRODUCTION: There are predictive algorithms for predicting 3-month and 1-year survival in patients with spinal metastasis. However, advance in surgical technique, immunotherapy, and advanced radiation therapy has enabled shortening of postoperative recovery, which returns dividends to the overall quality-adjusted life-year. As such, the Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) was proposed to predict 6-week survival in patients with spinal metastasis, whereas its utility for patients treated with nonsurgical treatment was untested externally. This study aims to validate the survival prediction of the 6-week SORG-MLA for patients with spinal metastasis and provide the measurement of model consistency (MC). METHODS: Discrimination using area under the receiver operating characteristic curve, calibration, Brier score, and decision curve analysis were conducted to assess the model's performance in the Taiwanese-based cohort. MC was also applied to detect the proportion of paradoxical predictions among 6-week, 3-month, and 1-year survival predictions. The long-term prognosis should not be better than the shorter-term prognosis in that of an individual. RESULTS: The 6-week survival rate was 84.2%. The SORG-MLA retained good discrimination with an area under the receiver operating characteristic curve of 0.78 (95% confidence interval, 0.75 to 0.80) and good prediction accuracy with a Brier score of 0.11 (null model Brier score 0.13). There is an underestimation of the 6-week survival rate when the predicted survival rate is less than 50%. Decision curve analysis showed that the model was suitable for use over all threshold probabilities. MC showed suboptimal consistency between 6-week and 90-day survival prediction (78%). CONCLUSIONS: The results of this study supported the utility of the algorithm. The online tool ( https://sorg-apps.shinyapps.io/spinemetssurvival/ ) can be used by both clinicians and patients in informative decision-making discussion before management of spinal metastasis.

Effects of intravascular photobiomodulation on cognitive impairment and crossed cerebellar diaschisis in patients with traumatic brain injury: a longitudinal study.

The association between intravascular photobiomodulation (iPBM) and crossed cerebellar diaschisis (CCD) and cognitive dysfunction in patients with traumatic brain injury (TBI) remains unknown. We postulate that iPBM might enable greater neurologic improvements. The objective of this study was to evaluate the clinical impact of iPBM on the prognosis of patients with TBI. In this longitudinal study, patients who were diagnosed with TBI were recruited. CCD was identified from brain perfusion images when the uptake difference of both cerebella was > 20%. Thus, two groups were identified: CCD( +) and CCD( -). All patients received general traditional physical therapy and three courses of iPBM (helium-neon laser illuminator, 632.8 nm). Treatment assemblies were conducted on weekdays for 2 consecutive weeks as a solitary treatment course. Three courses of iPBM were performed over 2-3 months, with 1-3 weeks of rest between each course. The outcomes were measured using the Rancho Los Amigos Levels of Cognitive Functioning (LCF) tool. The chi-square test was used to compare categorical variables. Generalized estimating equations were used to verify the associations of various effects between the two groups. p < 0.05 indicated a statistically significant difference. Thirty patients were included and classified into the CCD( +) and CCD( -) groups (n = 15, each group). Statistics showed that before iPBM, CCD in the CCD( +) group was 2.74 (exp 1.0081) times higher than that of CCD( -) group (p = 0.1632). After iPBM, the CCD was 0.64 (exp-0.4436) times lower in the CCD( +) group than in the CCD( -) group (p < 0.0001). Cognitive assessment revealed that, before iPBM, the CCD( +) group had a non-significantly 0.1030 lower LCF score than that of CCD( -) group (p = 0.1632). Similarly, the CCD( +) group had a non-significantly 0.0013 higher score than that of CCD( -) after iPBM treatment (p = 0.7041), indicating no significant differences between the CCD( +) or CCD( -) following iPBM and general physical therapy. CCD was less likely to appear in iPBM-treated patients. Additionally, iPBM was not associated with LCF score. Administration of iPBM could be applied in TBI patients to reduce the occurrence of CCD. The study failed to show differences in cognitive function after iPBM, which still serves as an alternative non-pharmacological intervention.

Insulin Resistance Indices and Carotid Intima-media Thickness in Physically Fit Adults: CHIEF Atherosclerosis Study.

AIMS: This study aims to examine the associations between various non-insulin-based insulin resistance (nIIR) indices and subclinical atherosclerosis assessed by carotid intima-media thickness (cIMT) in young adults. BACKGROUND: nIIR indices, e.g., serum triglycerides (TG) have been reported with an association with cIMT in middle- and old-aged adults. OBJECTIVE: We examined the associations of various well-known nIIR indices reported before with cIMT in young adults. METHODS: A total of 1,822 young adults free of diabetes in Taiwan were included in 2018-2020. nIIR indices were assessed by TG concentrations, the TyG index, defined as Ln (TG *fasting glucose/2), the TG/high-density lipoprotein cholesterol (HDL-C) ratio, defined as TG divided by HDL-C, and the metabolic score for IR (METS-IR), defined as Ln[(2*fasting glucose)+TG) * body mass index (BMI)/(Ln(HDL-C))]. Multivariable linear regression analyses with adjustments for age, sex, anthropometrics, smoking, alcohol consumption, blood pressure, and total cholesterol were used to determine the associations. For TG only, HDL-C and fasting glucose were additionally adjusted. RESULTS: In the overall participants, there was an association between cIMT and TG (ß: 0.057, p = 0.04). In subgroup analyses, cIMT was associated with TG (ß: 0.127, p = 0.004), the TyG index (ß: 0.119, p = 0.01), and TG/HDL-C (ß: 0.081, p = 0.03) in the overweight / obese (BMI ≥25 kg/m2), while not in the normal weight individuals. However, cIMT was correlated with TG (ß: 0.086, p = 0.01) and TG/HDL-C (ß: 0.077, p = 0.01) in those without hyperuricemia, while not in those with hyperuricemia. No association between the METS-IR and cIMT in any young adult subgroups was observed. CONCLUSION: This study highlights that some nIIR indices could be used to assess cIMT in young adults, particularly for those with obesity and those without hyperuricemia. The TG-based indices instead of the novel marker, METS-IR, are suggestive as stronger predictors of greater cIMT in young adults.

Electrocardiographic and echocardiographic predictors of greater carotid intima-media thickness in tactical athletes: The CHIEF atherosclerosis study.

OBJECTIVE: Both electrocardiographic and echocardiographic left ventricular hypertrophy (LVH) have been reported with an association with greater carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis in patients with hypertension, while the associations are unclear in physically fit young adults. METHODS: A total of 1822 Taiwanese military personnel, aged 18-40 years, received an annual health examination including electrocardiography (ECG) and echocardiography in 2018-2020. Left carotid bulb cIMT was measured by high-resolution ultrasonography. Multiple logistic regression analysis with adjustments for age, sex, smoking, alcohol consumption, body mass index, mean blood pressure, and physical fitness was used to determine the associations between echocardiographic and ECG parameters and the highest quintile of cIMT (≥0.8 mm). RESULTS: Cornell-based LVH, Myers et al.-based RVH and heart rate ≥75/min were associated with cIMT ≥0.8 mm [odds ratios (ORs) and 95% confidence intervals: 1.54 (1.01, 2.35), 1.66 (1.18, 2.33), and 1.39 (1.06, 1.83), respectively], while echocardiographic LVH defined as ≥46.0 g/m2.7 for men and ≥38.0 g/m2.7 for women was inversely associated with cIMT ≥0.8 mm [OR: 0.45 (0.24, 0.86)]. CONCLUSION: In tactical athletes of military, the associations of ECG and echocardiographic LVH with cIMT were in opposite directions. Higher physical fitness may cause cardiac muscle hypertrophy and reduce the atherosclerosis severity, possibly leading to the paradoxical echocardiographic finding. This study suggests that ECG-based LVH remains a good marker of subclinical atherosclerosis in our military population.

Non-Insulin-Based Insulin Resistance Indices and Localized Periodontitis in Physically Active Young Male Adults: CHIEF Oral Health Study.

AIMS: This study aims to examine the association between non-insulin-based insulin resistance indices and periodontitis severity in young males. BACKGROUND: Periodontitis has been reported with an association with insulin resistance in middle- and old-aged adults. OBJECTIVE: The association between insulin resistance and localized periodontitis in young adults is unclear. METHODS: A total of non-diabetic 1,111 military males in Taiwan were included in this study. Localized periodontitis was classified as healthy (N =665), stage I (N =130), stage II (N =161), and stage III (N =155) based on the world workshop in 2017. Insulin resistance was assessed by serum triglycerides concentrations, the triglycerides glucose (TyG) index, the product of serum triglycerides and fasting glucose, and the ratio of serum triglycerides to high-density lipoprotein cholesterol (TG/HDL-C). Multiple logistic regression analysis with adjustment for age, tobacco smoking, alcohol intake, abdominal obesity, and hypertension was used to determine the associations. RESULTS: Serum TG concentrations, TyG index, and TG/HDL-C ratio were dose-dependently associated with a greater risk of localized periodontitis severity (from stage I to stage III) [odds ratios and 95% confidence intervals: 1.001 (0.999-1.004), 1.003 (1.001-1.004) and 1.003 (1.002- 1.005) for TG; 1.45 (1.03-2.03), 1.65 (1.22-2.22) and 1.66 (1.22-2.26) for TyG index; 1.06 (0.99- 1.14), 1.09 (1.03-1.15) and 1.10 (1.04-1.16) for TG/HDL-C ratio]. However, the association was only found in obese individuals and those free of impaired fasting glucose. CONCLUSION: The present study confirmed that periodontitis may lead to insulin resistance in young male adults, particularly for those with obesity and without hyperglycemia. The TyG index is suggestive as the strongest indicator for the association between insulin resistance and periodontitis in young adults.

Hepatic and Systemic Inflammation for Left Ventricular Mass in Physically Fit Adults: CHIEF Heart Study.

BACKGROUND: Both low-grade systemic and hepatic inflammation could result in increased left ventricular mass (LVM) in the general population. However, the associations, which might be modified by exercise, have not been clarified in physically active young adults. METHODS: The study included 2,004 military males aged 18-43 years in eastern Taiwan. Systemic and hepatic inflammation was defined by the upper tertiles of blood white blood cell (WBC) counts (7.51-11.00 x 103/µL) and serum alanine aminotransferase (ALT: 30-120 U/L), respectively. LVM indexed for the body height ≥49 g/m2.7 was defined as left ventricular hypertrophy (LVH) based on echocardiography. Multiple logistic regression analysis adjusting for age, smoking, alcohol intake, physical fitness, and metabolic syndrome was utilized to determine the associations. RESULTS: As compared to the lower WBC/lower ALT group, there tended to have an increased risk of LVH with the higher WBC/lower ALT group, the lower WBC/higher ALT group, and the higher WBC/higher ALT group [odds ratios: 0.89 (95% confidence intervals (CI): 0.41-1.94), 1.90 (95% CI: 0.86-4.22) and 2.48 (95% CI: 1.04-5.92); p-value for trend = 0.01]. CONCLUSION: Our study suggested that in physically active males, those with hepatic inflammation rather than low-grade systemic inflammation had a higher risk of LVH. Hepatic injury might be relevant to LVH as an early sign of end-organ damage regardless of physical fitness in young adults.

Generalizable transfer learning of automated tumor segmentation from cervical cancers toward a universal model for uterine malignancies in diffusion-weighted MRI.

PURPOSE: To investigate the generalizability of transfer learning (TL) of automated tumor segmentation from cervical cancers toward a universal model for cervical and uterine malignancies in diffusion-weighted magnetic resonance imaging (DWI). METHODS: In this retrospective multicenter study, we analyzed pelvic DWI data from 169 and 320 patients with cervical and uterine malignancies and divided them into the training (144 and 256) and testing (25 and 64) datasets, respectively. A pretrained model was established using DeepLab V3 + from the cervical cancer dataset, followed by TL experiments adjusting the training data sizes and fine-tuning layers. The model performance was evaluated using the dice similarity coefficient (DSC). RESULTS: In predicting tumor segmentation for all cervical and uterine malignancies, TL models improved the DSCs from the pretrained cervical model (DSC 0.43) when adding 5, 13, 26, and 51 uterine cases for training (DSC improved from 0.57, 0.62, 0.68, 0.70, p < 0.001). Following the crossover at adding 128 cases (DSC 0.71), the model trained by combining data from adding all the 256 patients exhibited the highest DSCs for the combined cervical and uterine datasets (DSC 0.81) and cervical only dataset (DSC 0.91). CONCLUSIONS: TL may improve the generalizability of automated tumor segmentation of DWI from a specific cancer type toward multiple types of uterine malignancies especially in limited case numbers.

Associations of decayed teeth and localized periodontitis with mental stress in young adults: CHIEF oral health study.

The associations of mental stress with decayed teeth in children and periodontitis in old-aged adults have been described. However, the associations for young adults were not clear. This study aimed to examine the associations of decayed teeth and localized periodontitis with mental stress in young adults. This study included 334 military recruiters, aged 19-45 years in Taiwan. Mental stress was assessed by the brief symptom rating scale-5 (BSRS-5), including five domains: anxiety, depression, hostility, interpersonal sensitivity and insomnia (maximum score of 20). Those with symptomatic mental stress were defined as having BSRS-5 > 5 (n = 34). Multiple linear and logistic regression models were used to determine the associations of decayed tooth numbers and periodontitis with BSRS-5, with adjustments for age, sex, education level, physical activity, body weight category and smoking status. The BSRS-5 was positively correlated with decayed tooth numbers [ß: 0.26 (95% confidence interval: 0.01-0.52)]. Those who had more than two decayed teeth [odds ratio: 3.59 (1.52-8.46)] had a higher risk of symptomatic mental stress. In contrast, the correlation between BSRS-5 and localized severer periodontitis was null. Our study recommended that decayed teeth instead of localized periodontitis, was a risk factor for mental stress in young adults.

Dental caries and periodontitis and the risk of myopia in young adults: CHIEF oral health study.

AIM: Oral health and ocular diseases may be associated with collagen defects and inflammation status. However, the results from prior studies are conflicting. The aim of this study was to explore the association of dental caries and periodontitis with myopia in young adults. MATERIALS AND METHODS: A total of 938 military personnel aged 19-39 years receiving both oral and eye examinations from 2018 through 2020 were included in this study in Taiwan. The severity of myopia was graded as no myopia (diopters > - 0.5, N = 459), low myopia (diopters: - 0.5 to -5.9, N = 225) and high myopia (diopters ≤ - 6.0, N = 254). A multiple logistic regression analysis with adjustments for age, body mass index, systolic blood pressure, smoking, alcohol consumption, missing teeth numbers, blood leucocyte counts, triglycerides, high-density lipoprotein, and uric acid were used to determine the associations of actively dental caries, filled teeth and stage II/III periodontitis with myopia. RESULTS: The presence of any actively dental caries was significantly associated with a higher risk of any myopia (low or high) (odds ratio [OR] and 95% confidence intervals [95% CI] 1.42 [1.04-1.94]), whereas there was no association for filled teeth. Moreover, the association for stage II/III periodontitis was only observed with high myopia (OR: 1.52 [1.07-2.15]) and was not observed with low myopia. CONCLUSIONS: Our findings suggest that only actively dental caries and a higher severity of periodontitis were associated with myopia among young adults, thus highlighting the dental inflammation status in the oral cavity as a potential link to ocular diseases.

A case of adult granulosa cell tumor of the ovary with long-term survival after multiple recurrences.

OBJECTIVE: To illustrate the clinical course of a rare case of recurrent adult granulosa cell tumor (AGCT) and discuss the features and management for recurrences. CASE REPORT: A 56-year-old female was first diagnosed with AGCT in 2008 and had uneventful, regular follow-ups until 2013. Recurrence was suspected and proven by computed tomography-guided biopsy. After undergoing complete cytoreductive surgery (CRS) followed by adjuvant megestrol acetate then leuprolide acetate, another recurrence sprouted at the presacral area in 2017. On both occasions, CRS with no visible residual tumor were attained. The patient has remained in complete remission to date with progestin therapy. CONCLUSION: There are currently no standardized tumor markers, imaging exams, or therapies for managing AGCT recurrences. Whole exome sequencing analysis of our patient suggested possible association with triosephosphate isomerase 1 mutation. Regular follow-ups with at least two types of imaging exams and indefinite hormone therapy are crucial for this patient's remission.

Erythrocyte indices and localized stage II/III periodontitis in military young men and women: CHIEF oral health study.

BACKGROUND: Prior studies have shown an association between generalized periodontitis and anemia in older or undernourished adults. The aim of the study was to examine the associations of erythrocyte indices with localized periodontitis in robust young adults, which has never been reported before. METHODS: The study included 1286 military participants, aged 19-40 years, with regular exercise training in Hualien, Taiwan. Localized periodontitis was grouped to healthy/stage I and stage II/III (n = 803 and 325) in men and (n = 130 and 28) in women according to the 2017 criteria of the world workshop. Systemic inflammation was evaluated by leukocyte counts. Multiple logistic regression analysis with adjustment for age, tobacco smoking status, betel nut chewing status, body mass index and leucocyte counts were used to determine the associations. RESULTS: Greater mean corpuscular volume in young men [odds ratio (OR) and 95% confidence intervals 1.03 (1.01-1.06)], and greater hematocrit and hemoglobin levels in young women were associated with a higher risk of localized stage II/III periodontitis [OR: 1.17 (1.02-1.34) and 1.60 (1.06-2.41), respectively]. However, there were no associations for erythrocyte counts. CONCLUSIONS: The localized stage II/III periodontitis risk increased with greater erythrocyte indices in robust young adults. This finding could be explained in part by that localized periodontitis may promote physical stress, possibly resulting in an increase of erythrocyte indices. On the other side, greater physical fitness associated with a lower risk of periodontitis may consume iron storage in the body, leading to exercise-induced anemia or smaller erythrocyte volume.

Associations of decayed and filled teeth with localized stage II/III periodontitis in young adults: The CHIEF oral health study.

Background/purpose: To investigate the associations between treated and untreated dental caries and periodontitis in young adults. Materials and methods: The study enrolled 1289 participants aged 18-45 years in Taiwan. Localized periodontitis was categorized into healthy and stage II/III (n = 936 and n = 353, respectively) based on the 2017 criteria of the World Workshop. Multivariable logistic regression analysis with adjustments for sex, age, tobacco smoking status, betel nut consumption status, metabolic syndrome, and total white blood cell count was used to determine the associations. Results: Decayed tooth numbers were positively associated with localized stage II/III periodontitis [odds ratio (OR): 1.15 (95% confidence intervals (CI): 1.06-2.25)], while filled tooth numbers were inversely associated with localized stage II/III periodontitis in young adults [OR: 0.96 (95% CI: 0.92-0.99)]. Conclusion: Our study confirms the relationship between dental caries and periodontitis by direct evidence that the more decayed teeth there are, the higher the risk of periodontitis and by indirect evidence that the more treated decayed teeth there are, the lower the risk of periodontitis in young adults.