Association of serum 25-hydroxyvitamin D with stroke: Observational mediation and Mendelian Randomization Study.

CONTEXT: The causal association and biological mechanism linking serum 25-hydroxyvitamin D to stroke risk lacks epidemiological evidence. OBJECTIVE: This study aimed to investigate the association between 25(OH)D concentration and stroke risk as well as the potential mediating factors. DESIGN: The community-based prospective community-based cohort study, the Chin-Shan Community Cardiovascular Cohort, was conducted from 1990 to December 2011, with external validation using a two-sample Mendelian randomization (MR) study. PATIENTS: A total of 1,778 participants with serum 25-hydroxyvitamin D data were enrolled. METHODS: In the CCCC observational study, the outcome was ascertained as stroke, while in the two-sample MR study, it was defined as ischemic stroke. Causal effects were estimated using restricted cubic spline analysis, COX proportional hazard ratios, mediation analysis, and two-sample MR. RESULTS: Over 12 years (21,598 person-years) of follow-up, 163 participants (9.17%) developed stroke. Higher 25(OH)D concentrations were associated with lower stroke risk (hazard ratio: 0.64; 95% confidence interval, 0.43-0.96) after full-model adjustments. Mediation analysis showed a significant association between 25(OH)D concentration and stroke risk mediated by hypertension in unadjusted models (mediation percentage 23.3%, p=0.008) that became non-significant in full models (mediation percentage, 15.5%; p=0.072). Two-sample MR confirmed a significant inverse association between genetically determined 25(OH)D and stroke risk (IVW OR: 0.92; 95% CI: 0.85-0.99; p=0.036). However, hypertension had an insignificant mediating role in the Mendelian randomization study. CONCLUSIONS: Higher 25(OH)D levels are linked to reduced stroke risk, potentially mediated by hypertension. Prioritizing blood pressure management may improve stroke prevention in 25(OH)D-deficient patients.

Utilizing Artificial Neural Networks for Establishing Hearing-Loss Predicting Models Based on a Longitudinal Dataset and Their Implications for Managing the Hearing Conservation Program.

Background: Though the artificial neural network (ANN) technique has been used to predict noise-induced hearing loss (NIHL), the established prediction models have primarily relied on cross-sectional datasets, and hence, they may not comprehensively capture the chronic nature of NIHL as a disease linked to long-term noise exposure among workers. Methods: A comprehensive dataset was utilized, encompassing eight-year longitudinal personal hearing threshold levels (HTLs) as well as information on seven personal variables and two environmental variables to establish NIHL predicting models through the ANN technique. Three subdatasets were extracted from the afirementioned comprehensive dataset to assess the advantages of the present study in NIHL predictions. Results: The dataset was gathered from 170 workers employed in a steel-making industry, with a median cumulative noise exposure and HTL of 88.40 dBA-year and 19.58 dB, respectively. Utilizing the longitudinal dataset demonstrated superior prediction capabilities compared to cross-sectional datasets. Incorporating the more comprehensive dataset led to improved NIHL predictions, particularly when considering variables such as noise pattern and use of personal protective equipment. Despite fluctuations observed in the measured HTLs, the ANN predicting models consistently revealed a discernible trend. Conclusions: A consistent correlation was observed between the measured HTLs and the results obtained from the predicting models. However, it is essential to exercise caution when utilizing the model-predicted NIHLs for individual workers due to inherent personal fluctuations in HTLs. Nonetheless, these ANN models can serve as a valuable reference for the industry in effectively managing its hearing conservation program.

Effects of exercise on bone density and physical performance in postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Postmenopausal bone loss and decreased physical performance are commonly presented issues. This study aimed through systematic review and meta-analysis to examine the benefits of adding exercise to medicine/supplements in postmenopausal women. METHODS: A systematic search was conducted of four electronic databases for articles published from inception to December 2023. Clinical controlled trials comparing the effect of additional exercise and medicine/supplements alone in postmenopausal women were included. The outcomes studied were bone mineral density (BMD) and physical performance. The quality of evidence was evaluated by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Nineteen articles with 1249 participants were included in this study for systematic review and meta-analysis. The results showed that additional exercise was not associated with significantly improved BMD at the lumbar spine and hip joint compared with medicine/supplements only. However, results of subgroup analysis of exercise types showed a significant improvement in lumbar spine BMD by combining multiple types of exercise training (SMD = 0.37; 95% confidence interval [CI] = 0.01-0.72; p = .04). Furthermore, additional exercise significantly improved lower extremity muscle strength (Standard Mean Difference [SMD] = 1.77; 95% CI = 0.56-2.98; p = .004), Berg's Balance Scale (SMD = 0.72; 95% CI = 0.12-1.32; p = .02), Timed Up and Go (SMD = -1.07; 95% CI = -1.35--0.78; p < .001), fear of falling (SMD = 1.32; 95% CI = 0.89-1.75; p < .001), and the quality of life (SMD = 1.39; 95% CI = 0.74-2.05; p < .001). The quality level of the evidence was between low to very low. CONCLUSIONS: The significant value of the exercise was demonstrated through enhancing physical performance and quality of life. Moreover, combining various exercise training programs has shown a positive effect on BMD at the lumbar spine. Therefore, for postmenopausal women, combining exercise with medicine/supplements is recommended to further improve physical function and specific areas of BMD. (PROSPERO: CRD42023390633).

Impact of the prognostic nutritional index on renal replacement therapy-free survival and mortality in patients on continuous renal replacement therapy.

BACKGROUND: The survival of critically ill patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT) is highly dependent on their nutritional status. OBJECTIVES: The prognostic nutritional index (PNI) is an indicator used to assess nutritional status and is calculated as: PNI = (serum albumin in g/dL) × 10 + (total lymphocyte count in/mm3) × 0.005. In this retrospective study, we investigated the correlation between this index and clinical outcomes in critically ill patients with AKI receiving CRRT. METHODS: We analyzed data from 2076 critically ill patients admitted to the intensive care unit at Changhua Christian Hospital, a tertiary hospital in central Taiwan, between January 1, 2010, and April 30, 2021. All these patients met the inclusion criteria of the study. The relationship between PNI and renal replacement therapy-free survival (RRTFS) and mortality was examined using logistic regression models, Cox proportional hazard models, and propensity score matching. High utilization rate of parenteral nutrition (PN) was observed in our study. Subgroup analysis was performed to explore the interaction effect between PNI and PN on mortality. RESULTS: Patients with higher PNI levels exhibited a greater likelihood of achieving RRTFS, with an adjusted odds ratio of 2.43 (95% confidence interval [CI]: 1.98-2.97, p-value < 0.001). Additionally, these patients demonstrated higher survival rates, with an adjusted hazard ratio of 0.84 (95% CI: 0.72-0.98) for 28-day mortality and 0.80 (95% CI: 0.69-0.92) for 90-day mortality (all p-values < 0.05), compared to those in the low PNI group. While a high utilization rate of parenteral nutrition (PN) was observed, with 78.86% of CRRT patients receiving PN, subgroup analysis showed that high PNI had an independent protective effect on mortality outcomes in AKI patients receiving CRRT, regardless of their PN status. CONCLUSIONS: PNI can serve as an easy, simple, and efficient measure of lymphocytes and albumin levels to predict RRTFS and mortality in AKI patients with require CRRT.

Temperature dependence of pollen germination and tube growth in conifers relates to their distribution along an elevational gradient in Washington State, USA.

BACKGROUND AND AIMS: Pollen germination and tube growth are essential processes for successful fertilization. They are among the most temperature-vulnerable stages and subsequently affect seed production and determine population persistence and species distribution under climate change. Our study aims to investigate intra- and inter-specific variations in the temperature dependence of pollen germination and tube length growth and to explore how these variations differ for pollen from elevational gradients. METHODS: We focused on three conifer species, Pinus contorta, Picea engelmannii, and Pinus ponderosa, with pollen collected from 350 to 2200m elevation in Washington State, USA. We conducted pollen viability tests at temperatures from 5 to 40°C in 5°C intervals. After testing for four days, we took images of these samples under a microscope to monitor pollen germination percentage (GP) and tube length (TL). We applied the Gamma function to describe the temperature dependence of GP and TL and estimated key parameters, including the optimal temperature for GP (Topt_GP) and TL (Topt_TL). KEY RESULTS: Results showed that pollen from three species and different elevations within a species have different GP, TL, Topt_GP, and Topt_TL. The population with a higher Topt_GP would also have a higher Topt_TL, while Topt_TL was generally higher than Topt_GP, i.e., a positive but not one-to-one relationship. However, only Pinus contorta showed that populations from higher elevations have lower Topt_GP and Topt_TL and vice versa. The variability in GP increased at extreme temperatures, whereas the variability in TL was greatest near Topt_TL. CONCLUSIONS: Our study demonstrates the temperature dependences of three conifers across a wide range of temperatures. Pollen germination and tube growth are highly sensitive to temperature conditions and vary among species and elevations, affecting their reproduction success during warming. Our findings can provide valuable insights to advance our understanding of how conifer pollen responds to rising temperatures.

Systolic blood pressure as a critical mediator in the association between adult height and 25-year risk of stroke.

BACKGROUND: Adult height is associated with the risk of stroke. However, the underlying mechanism remains unclear. We explored the mediating role of metabolic factors in the association between adult height and stroke incidence. METHODS: We used data from 3306 community-dwelling participants with complete information on adult height, metabolic factors, and 25-year cardiovascular outcomes. Participants were classified into three adult height groups based on sex-specific height quartiles: short (Q1), average (Q2-Q3), and tall (Q4). The primary endpoint was the occurrence of cardiovascular disease, including coronary artery disease and stroke. RESULTS: Taller adult height was associated with a lower risk of stroke. Compared with the short group the risk of stroke reduced with taller height with a hazard ratio (HR) of 0.68 in the average group (95% confidence interval [CI]: 0.50-0.93), and 0.45 in the tall group (95% CI: 0.31-0.65). Low systolic blood pressure was considered as a protective mediator in the effect of adult height on the risk of stroke in the average (HR: 0.86; 95% CI: 0.82-0.93) and the tall group (HR: 0.85; 95% CI: 0.78-0.91). Systolic blood pressure significantly contributed to height-related stroke risk (proportion mediated: 0.41; 95% CI: 0.19-1.56). CONCLUSIONS: This study found an inverse association between adult height and stroke risk, which is partly driven by lower systolic blood pressure. These findings highlight the importance of systolic blood pressure management as a potential preventive strategy against stroke.

Colorectal Cancer and Subsequent Diabetes Risk: A Population-based Cohort Study in Taiwan.

CONTEXT: The association between colorectal cancer (CRC) and new-onset diabetes mellitus remains unclear. OBJECTIVE: To examine the association between CRC and the risk of subsequent diabetes mellitus and to further investigate the impact of chemotherapy on diabetes mellitus risk in CRC. DESIGN: A nationwide cohort study. METHODS: Using the Taiwan Cancer Registry Database (2007-2018) linked with health databases, 86,268 patients with CRC and an equal propensity score-matched cohort from the general population were enrolled. Among them, 37,277 CRC patients from the Taiwan Cancer Registry (2007-2016) were analyzed for diabetes mellitus risk associated with chemotherapy. Chemotherapy exposure within 3 years of diagnosis was categorized as no chemotherapy, <90 days, 90-180 days, and >180 days. Differences in diabetes mellitus risk were assessed across these categories. RESULTS: Each group involved 86,268 participants after propensity score matching. The patients with CRC had a 14% higher risk of developing diabetes mellitus than the matched general population (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.09-1.20). The highest risk was observed within the first year after diagnosis followed by a sustained elevated risk. Long-term chemotherapy (>180 days within 3 years) was associated with a 60-70% increased risk of subsequent diabetes mellitus (HR: 1.64, 95% CI: 1.07-2.49). CONCLUSION: Patients with CRC are associated with an elevated risk of diabetes mellitus, and long-term chemotherapy, particularly involving capecitabine, increases diabetes mellitus risk. Thus, monitoring blood glucose levels is crucial for patients with CRC, especially during extended chemotherapy.

Validating the Use of Percent Grammatical Utterances for Assessing Mandarin-Speaking Children's Grammatical Skill: Evidence From 3-Year-Olds.

PURPOSE: The study examined the use of percent grammatical utterances (PGUs) for assessing grammatical skills in Mandarin-speaking 3-year-old children. METHOD: Participants were 30 Mandarin-speaking 3-year-olds with typical development. Language samples were collected in two visits for each child using a picture description task. Children were asked to talk about 16 pictures in response to questions and prompts at each visit. Pictures for the language sample collection were identical across the visits. PGUs were computed, and the grammatical errors that children produced in the task were coded and tallied for error types at each visit. Test-retest reliability, split-half reliability, and concurrent criterion validity of PGUs were evaluated. RESULTS: The mean PGU level was approximately 78% at Visit 1 and 81% at Visit 2, both of which were significantly below the mastery level (i.e., 90%). The correlation coefficient for test-retest reliability of PGU was large (r = .70, p < .01); the correlation coefficient for split-half reliability was medium at Visit 1 (r = .47, p < .01) and large (r = .65, p < .01) at Visit 2. In addition, the correlation coefficient for concurrent criterion validity of PGU was medium for both visits (rs ≥ .35, ps ≤ .03). The ranking and proportion of each error type were similar between the visits. CONCLUSION: The initial evidence from psychometric properties suggests that PGU computed from the picture description task is a reliable and valid measure for evaluating grammatical skills in Mandarin-speaking 3-year-old children. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25395499.

Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer.

Rationale: Multiple copies in T-cell malignancy 1 (MCT-1) is a prognostic biomarker for aggressive breast cancers. Overexpressed MCT-1 stimulates the IL-6/IL-6R/gp130/STAT3 axis, which promotes epithelial-to-mesenchymal transition and cancer stemness. Because cancer stemness largely contributes to the tumor metastasis and recurrence, we aimed to identify whether the blockade of MCT-1 and IL-6R can render these effects and to understand the underlying mechanisms that govern the process. Methods: We assessed primary tumor invasion, postsurgical local recurrence and distant metastasis in orthotopic syngeneic mice given the indicated immunotherapy and MCT-1 silencing (shMCT-1). Results: We found that shMCT-1 suppresses the transcriptomes of the inflammatory response and metastatic signaling in TNBC cells and inhibits tumor recurrence, metastasis and mortality in xenograft mice. IL-6R immunotherapy and shMCT-1 combined further decreased intratumoral M2 macrophages and T regulatory cells (Tregs) and avoided postsurgical TNBC expansion. shMCT-1 also enhances IL-6R-based immunotherapy effectively in preventing postsurgical TNBC metastasis, recurrence and mortality. Anti-IL-6R improved helper T, cytotoxic T and natural killer (NK) cells in the lymphatic system and decreased Tregs in the recurrent and metastatic tumors. Combined IL-6R and PD-L1 immunotherapies abridged TNBC cell stemness and M2 macrophage activity to a greater extent than monotherapy. Sequential immunotherapy of PD-L1 and IL-6R demonstrated the best survival outcome and lowest postoperative recurrence and metastasis compared with synchronized therapy, particularly in the shMCT-1 context. Multiple positive feedforward loops of the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 axis were identified in TNBC cells, which boosted metastatic niches and immunosuppressive microenvironments. Clinically, MCT-1high/PD-L1high/CXCL7high and CXCL7high/IL-6high/IL-6Rhigh expression patterns predict worse prognosis and poorer survival of breast cancer patients. Conclusion: Systemic targeting the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 interconnections enhances immune surveillance that inhibits the aggressiveness of TNBC.

Eicosapentaenoic Acid Modulates Transient Receptor Potential V1 Expression in Specific Brain Areas in a Mouse Fibromyalgia Pain Model.

Pain is an unpleasant sensory and emotional experience accompanied by tissue injury. Often, an individual's experience can be influenced by different physiological, psychological, and social factors. Fibromyalgia, one of the most difficult-to-treat types of pain, is characterized by general muscle pain accompanied by obesity, fatigue, sleep, and memory and psychological concerns. Fibromyalgia increases nociceptive sensations via central sensitization in the brain and spinal cord level. We used intermittent cold stress to create a mouse fibromyalgia pain model via a von Frey test (day 0: 3.69 ± 0.14 g; day 5: 2.13 ± 0.12 g). Mechanical pain could be reversed by eicosapentaenoic acid (EPA) administration (day 0: 3.72 ± 0.14 g; day 5: 3.69 ± 0.13 g). A similar trend could also be observed for thermal hyperalgesia. The levels of elements in the transient receptor potential V1 (TRPV1) signaling pathway were increased in the ascending pain pathway, including the thalamus, medial prefrontal cortex, somatosensory cortex, anterior cingulate cortex, and cerebellum. EPA intake significantly attenuated this overexpression. A novel chemogenetics method was used to inhibit SSC and ACC activities, which presented an analgesic effect through the TRPV1 downstream pathway. The present results provide insights into the role of the TRPV1 signaling pathway for fibromyalgia and its potential as a clinical target.

Validating the accuracy of the Hendrich II Fall Risk Model for hospitalized patients using the ROC curve analysis.

This retrospective study was conducted at a medical center in southern Taiwan to assess the accuracy of the Hendrich II Fall Risk Model (HIIFRM) in predicting falls. Sensitivity, specificity, accuracy, and optimal cutoff points were analyzed using receiver operating characteristic (ROC) curves. Data analysis was conducted using information from the electronic medical record and patient safety reporting systems, capturing 303 fall events and 47,146 non-fall events. Results revealed that at the standard threshold of HIIFRM score ≥5, the median score in the fall group was significantly higher than in the non-fall group. The top three units with HIIFRM scores exceeding 5 were the internal medicine (50.6%), surgical (26.5%), and oncology wards (14.1%), indicating a higher risk of falls in these areas. ROC analysis showed an HIIFRM sensitivity of 29.5% and specificity of 86.3%. The area under the curve (AUC) was 0.57, indicating limited discriminative ability in predicting falls. At a lower cutoff score (≥2), the AUC was 0.75 (95% confidence interval: 0.666-0.706; p < 0.0001), suggesting acceptable discriminative ability in predicting falls, with an additional identification of 101 fall events. This study emphasizes the importance of selecting an appropriate cutoff score when using the HIIFRM as a fall risk assessment tool. The findings have implications for fall prevention strategies and patient care in clinical settings, potentially leading to improved outcomes and patient safety.

Chemogenetics Modulation of Electroacupuncture Analgesia in Mice Spared Nerve Injury-Induced Neuropathic Pain through TRPV1 Signaling Pathway.

Neuropathic pain, which is initiated by a malfunction of the somatosensory cortex system, elicits inflammation and simultaneously activates glial cells that initiate neuroinflammation. Electroacupuncture (EA) has been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We suggest that EA can reliably cure neuropathic disease through anti-inflammation and transient receptor potential V1 (TRPV1) signaling pathways from the peripheral to the central nervous system. To explore this, we used EA to treat the mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetics techniques. Both mechanical and thermal pain were found in SNI mice at four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Mechanical hyperalgesia was partially attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g), and thermal hyperalgesia was fully reduced (thermal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), suggesting EA's specificity. In addition, animals with Trpv1 deletion showed partial mechanical hyperalgesia and no significant induction of thermal hyperalgesia in neuropathic pain mice (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-ß), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in the EA and Trpv1-/- groups rather than the sham group. Western blot and immunofluorescence analysis showed similar tendencies in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity, which showed an analgesic effect through the TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as a beneficial target for neuropathic pain.

Impaired motor skills and proprioceptive function in Mandarin-speaking children with developmental language disorder.

This study examined proprioceptive acuity and its relationship with motor function in Mandarin-speaking children with and without developmental language disorder (DLD). Fifteen children aged 9-12 years with DLD and 15 age- and sex-matched typically developing (TD) children participated in this study. Children's motor function was assessed using the second edition of the Movement Assessment Battery for Children (MABC-2). Their proprioceptive acuity was measured based on the absolute error (i.e., proprioceptive bias) and variable error (i.e., proprioceptive precision) when performing joint position matching tasks. Compared with the TD group, the DLD group exhibited impaired motor function and poorer proprioceptive acuity, as evidenced by the lower scores on the MABC-2 and the higher rates of absolute and variable errors in the joint position matching tasks. A significant association between the proprioceptive bias (absolute error) and the MABC-2 total score was also observed in the combined cohort of children with and without DLD. We conclude that DLD is associated with proprioceptive dysfunction.

Acupoint catgut embedding attenuates fibromyalgia pain through attenuation of TRPV1 signaling pathway in mouse.

Objectives: Chronic pain is considered as pain lasting for more than three months and has emerged as a global health problem affecting individuals and society. Chronic extensive pain is the main syndrome upsetting individuals with fibromyalgia (FM), accompanied by anxiety, obesity, sleep disturbances, and depression, Transient receptor potential vanilloid 1 (TRPV1) has been reported to transduce inflammatory and pain signals to the brain. Materials and Methods: Acupoint catgut embedding (ACE) is a novel acupuncture technique that provides continuous effects and convenience. ACE was performed at the bilateral ST36 acupoint. Results: We demonstrated similar pain levels among all groups at baseline. After cold stress, chronic mechanical or thermal nociception was induced (D14: mechanical: 1.85 ± 0.13 g; thermal: 4.85 ± 0.26 s) and reversed in ACE-treated mice (D14: mechanical: 3.99 ± 0.16 g; thermal: 7.42 ± 0.45 s) as well as Trpv1-/- group (Day 14, mechanical: 4.25 ± 0.2 g; thermal: 7.91 ± 0.21 s) mice. Inflammatory mediators were augmented in FM individuals and were abridged after ACE management and TRPV1 gene loss. TRPV1 and its linked mediators were increased in the thalamus (THA), somatosensory cortex (SSC), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) in FM mice. The up-regulation of these mediators was diminished in ACE and Trpv1-/- groups. Conclusion: We suggest that chronic pain can be modulated by ACE or Trpv1-/-. ACE-induced analgesia via TRPV1 signaling pathways may be beneficial targets for FM treatment.

The Risk of Cancer-Associated and Radiotherapy-Associated Cardiovascular Diseases among Patients with Breast Cancer.

BACKGROUND: The cardio-related issues should be emphasized as the survival rates of breast cancer increased. We investigated the risk of coronary artery disease (CAD) and stroke due to breast cancer or radiotherapy. METHODS: In this retrospective cohort study, breast cancer patients diagnosed between 2007 and 2016 were recruited from Taiwan Cancer Registry Database and were followed until the end of 2018 by linking with the Taiwan National Health Insurance Database. The general population was randomly selected from the whole population in 2007. Standardized incidence ratios (SIR) were calculated to compare the risk of CAD and stroke between patients and the general population. Within the cohort, we included the patients diagnosed between 2011 and 2016. Cox proportional hazards model and subdistribution hazard function were used to investigate the associations of radiotherapy with the risk of CAD and stroke. RESULTS: Overall SIR of CAD was 0.82 (95% confidence interval [CI]: 0.78-0.86), while were 1.43 and 1.08 (95% CI: 1.30-1.55 and 1.00-1.16) 1 and 2 years after diagnosis, respectively. Overall SIR of stroke was 0.63 (95% CI: 0.60-0.67), the results were similar after considering the time since diagnosis. The adjusted hazard ratios (HR) for the associations of radiotherapy with CAD and stroke risk were 0.91 (95% [CI] = 0.76-1.09) and 0.84 (95% CI = 0.68-1.04), respectively. The results were similar by using subdistribution hazard function. CONCLUSIONS: The risk of CAD was higher within the first 2 years of breast cancer diagnosis. We found no association between radiotherapy and the risk of CAD and stroke.

Tumor Marker Trajectories and Survival Analysis in Patients With Normal Carcinoembryonic Antigen Ranges After Colorectal Cancer Resection.

BACKGROUND: Evidence regarding postoperative CEA for predicting long-term outcomes of colorectal cancer remains controversial, especially in patients with normal postoperative CEA. OBJECTIVE: To investigate the risk difference among different postoperative CEA trajectories in patients with normal postoperative CEA after curative colorectal cancer resection. DESIGN: This cohort study was conducted at a comprehensive cancer center and included data retrieved from a prospectively collected database between January 2006 and December 2018. SETTINGS: Retrospective cohort study. PATIENTS: Patients with colorectal cancer who underwent surgery for primary stage I to III colorectal adenocarcinoma were included and those with postoperative CEA >5 ng/mL were excluded. INTERVENTIONS: Standard curative radical resection was performed. MAIN OUTCOME MEASURES: Ten-year overall survival and disease-free survival were analyzed. RESULTS: The study population (n = 8156) was categorized into 6 trajectories: persistent-ultralow (n = 2351), persistent-low (n = 2474), gradually decrease (n = 401), persistent-medium (n = 1727), slightly increase (n = 909), and around-upper-limit (n = 394). The median follow-up time was 7.8 years, and the median time frame in which CEA was measured to determine trajectory was 2.6 years. The persistent-ultralow group had the highest 10-year overall survival (85.1%) and disease-free survival (82.7%). The around-upper-limit group had the lowest 10-year overall survival (55.5%) and disease-free survival (53.4%). The adjusted HR trend was comparable to the crude HR of the persistent-ultralow group. Consequently, the higher initial serum CEA groups had higher HRs of overall survival and disease-free survival. The adjusted HR of overall survival was 2.96 (95% CI, 2.39-3.66) and of disease-free survival was 2.66 (95% CI, 2.18-3.69) for the around-upper-limit groups. LIMITATIONS: Retrospective design. CONCLUSIONS: The postoperative serum CEA trajectory is an independent factor associated with long-term outcomes. Although CEA levels were all within normal range, higher levels of postoperative serum CEA trajectory correlated with worse long-term oncological outcomes. See Video Abstract. TRAYECTORIAS DE MARCADORES TUMORALES Y ANLISIS DE SUPERVIVENCIA EN PACIENTES CON RANGOS NORMALES DE ANTGENO CARCINOEMBRIONARIO POSTERIOR A RESECCIN DE CNCER COLORRECTAL: ANTECEDENTES:La evidencia sobre el CEA post operatorio para la predicción de los resultados a largo plazo del cáncer colorrectal sigue siendo controversial, especialmente en pacientes con CEA post quirúrgico normal.OBJETIVO:Investigar la diferencia de riesgo entre diferentes trayectorias postoperatorias del CEA en pacientes con CEA post quirúrgico normal tras la resección curativa del cáncer colorrectal.DISEÑO:Este estudio de cohorte se realizó en un centro oncológico integral e incluyó datos recuperados de una base de datos recopilada prospectivamente entre enero de 2006 y diciembre de 2018.AJUSTES:Estudio de cohorte retrospectivo.PACIENTES:Se incluyeron pacientes con el diagnostico de CCR que fueron sometidos a cirugía por adenocarcinoma colorrectal primario en estadio I-III. Se excluyeron pacientes con CEA postoperatorio >5 ng/mL.INTERVENCIONES:Se realizó una resección radical curativa estandarizada.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron la supervivencia general a diez años y la supervivencia libre de enfermedad.RESULTADOS:La población de estudio (n = 8156) fue clasificada en seis trayectorias, que incluyeron ultrabajo persistente (n = 2351), bajo persistente (n = 2474), disminución gradual (n = 401), medio persistente (n = 1727), aumento leve (n = 909) y alrededor del límite superior (n = 394). La mediana del tiempo de seguimiento fue de 7,8 años y la mediana del período de tiempo en el que el CEA fue medido para determinar la trayectoria fue de 2,6 años. El grupo ultrabajo persistente tuvo la mayor supervivencia general a 10 años (85,1 %) y supervivencia libre de enfermedad (82,7 %). El grupo alrededor del límite superior tuvo la supervivencia general a 10 años más baja (55,5 %) y la supervivencia libre de enfermedad (53,4 %). La tendencia del índice de riesgo ajustado fue comparable al índice de riesgo bruto del grupo ultrabajo persistente. En consecuencia, los grupos con CEA sérico iniciales más altos tenían índices de riesgos más altos de supervivencia general y supervivencia libre de enfermedad. Los índices de riesgos ajustados de supervivencia general/supervivencia libre de enfermedad fueron 2,96/2,66 (intervalo de confianza del 95 %: 2,39-3,66/2,18-3,69) para los grupos cercanos al límite superior.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:La trayectoria del CEA sérico postoperatorio es un factor independiente asociado con resultados a largo plazo. Aunque los niveles de CEA se encontraban todos dentro del rango normal, los niveles más altos de trayectoria del CEA en suero posoperatorio se correlacionaron con peores resultados oncológicos a largo plazo. (Traducción-Dr Osvaldo Gauto ).

Sleep and rest-activity rhythms for women at different menopausal statuses: the role of mental health.

OBJECTIVE: To examine how mental health interplays with menopausal status in relation to sleep patterns and rest-activity rhythms (RARs) among middle-aged women. METHODS: This cross-sectional study recruited 87 women aged 45 to 60 years from community and a gynecology clinic in Taiwan. Participants wore actigraphy devices for 7 days and were also assessed with self-reported questionnaires. Hierarchical regression was used to examine the effects of menopausal status and mental health on sleep and RARs. RESULTS: Perimenopausal and postmenopausal women had higher relative amplitude and interdaily stability of RARs than premenopausal women. There were no differences in actigraphy-based sleep parameters across menopausal statuses. There was no difference in depressive symptoms or loneliness across menopausal statuses. Higher levels of depressive symptoms were significantly associated with longer sleep latency ( ß = 0.26, P = 0.022) and wake after sleep onset ( ß = 0.28, P = 0.012), and lower sleep efficiency ( ß = -0.30, P = 0.008) after adjusting for menopausal status and age. In addition, there was marginal significance of the positive association between loneliness and interdaily stability ( ß = 0.18, P = 0.079). A moderating effect ( ßmenopausal status*loneliness = -0.40, P = 0.025) showed that lonelier premenopausal women exhibited greater relative amplitude (RA) of rest-activity rhythms, but lonelier menopausal women had lower RA of RAR. CONCLUSION: Mental health plays an important role for middle-aged women with different menopausal statuses in relation to sleep patterns and RARs.

Cancer Fear, Emotion Regulation, and Emotional Distress in Patients With Newly Diagnosed Lung Cancer.

BACKGROUND: Research related to newly diagnosed lung cancer patients' emotional regulation strategies and how these strategies influence their emotional distress is scarce. OBJECTIVE: The aim of this study was to investigate the relationship between cancer fear, emotion regulation, and emotional distress in patients with newly diagnosed lung cancer. METHOD: A cross-sectional, correlation research design was conducted, using self-report questionnaires: the Cancer Fear Scale, the Emotion Regulation Questionnaire, and the Hospital Anxiety and Depression Scale. A total of 117 newly diagnosed lung cancer patients were sampled. RESULTS: Nearly 70% of newly diagnosed lung cancer patients had a high level of cancer fear; 56.4%, depression; and 45.3%, anxiety. Depression was positively associated with cancer fear ( r = 0.239, P < .01) and expressive suppression ( r = 0.185, P < .05), but negatively associated with cognitive reappraisal ( r = -0.323, P < .01). Anxiety was positively associated with cancer fear ( r = 0.488, P < .01) but negatively associated with cognitive reappraisal ( r = -0.214, P < .05). Cancer fear and cognitive reappraisal were significant explanatory factors and explained 25.2% of variance in anxiety. Cancer fear, expressive suppression, and cognitive reappraisal were significant explanatory factors and explained 16.7% of variance in depression. CONCLUSIONS: Newly diagnosed lung cancer patients with cancer fear and who used fewer cognitive reappraisal strategies or more expressive suppression had more emotional distress. IMPLICATIONS FOR PRACTICE: Clinicians should be attentive to patients' cancer fears and emotion regulation strategies as early as possible to prevent their emotional distress.