RESUMEN

OBJECTIVE: Major lower limb amputation is a disfiguring operation associated with impaired mobility and high near-term mortality. Informed decision-making regarding amputation requires outcomes data. Despite the co-occurrence of both chronic limb-threatening ischemia (CLTI) and Alzheimer's Disease and related dementias (ADRD), there is sparse data on the outcomes of major limb amputation in this population and the impact of frailty. We sought to determine mortality, complications, readmissions, revisions, intensive interventions (e.g., cardiopulmonary resuscitation), and other outcomes after amputation for CLTI in patients living with ADRD looking at the modifying effects of frailty. METHODS: We examined Medicare fee-for-service claims data from January 1, 2016 to December 31, 2020. Patients with CLTI undergoing amputation at or proximal to the ankle were included. Along with demographic information, dementia status, and comorbid conditions, we measured frailty using a claims-based frailty index. We dichotomized dementia and frailty (pre-frail/robust = "non-frail" vs moderate/severe frailty = "frail") to create four groups: non-frail/non-ADRD, frail/non-ADRD, non-frail/ADRD, and frail/ADRD. We used linear and logistic regression via generalized estimating equations in addition to performing selected outcomes analyses with death as a competing risk to understand the association between dementia status, frailty status, and one-year mortality as our primary outcome in addition to the postoperative outcomes outlined above. RESULTS: Among 46,930 patients undergoing major limb amputation, 11,465 (24.4%) had ADRD and 24,790 (52.8%) had frailty. Overall, 55.9% of amputations were below-knee. Selected outcomes among frail/ADRD patients undergoing amputation (N=10,153) were: 55.3% one-year mortality 29.6% readmissions at 30 days, and 32.3% amputation revision/reoperation within one year. Of all four groups, those in the frail/ADRD had the worst outcomes only for 1-year mortality. CONCLUSIONS: First, patients with ADRDw or moderate/severe frailty suffer an array of very poor outcomes after major limb amputation for CLTI including high mortality, readmissions, revision, and risks of discharge to higher levels of care. Second, there is a complex relationship between outcome severity and ADRD/frailty status. Specifically, frailty is more often than ADRD associated with the poorest results for any given outcome. These data provide important outcomes data to help align decision-making with healthcare values and goals.

RESUMEN

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.

Asunto(s)

RESUMEN

Betaine is the major water-soluble component of Lycium chinensis. Although there are reports of a protective effect of betaine on fatty liver disease, the underlying mechanisms are unclear. We attempted to elucidate the molecular regulation of betaine on hyperglycemia-induced hepatic lipid accumulation via Forkhead box O (FoxO)6 activation. HepG2 cells and liver tissue isolated from db/db mice treated with betaine were used. The present study investigated whether betaine ameliorates hepatic steatosis by inhibiting FoxO6/peroxisome proliferator-activated receptor gamma (PPARγ) signaling in liver cells. Interestingly, betaine notably decreased lipid accumulation in tissues with FoxO6-induced mRNA expression of lipogenesis-related genes. Furthermore, betaine inhibited the FoxO6 interaction with PPARγ and cellular triglycerides in high-glucose- or FoxO6-overexpression-treated liver cells. In addition, we confirmed that betaine administration via oral gavage significantly ameliorated hepatic steatosis in db/db mice. We conclude that betaine ameliorates hepatic steatosis, at least in part, by inhibiting the interaction between FoxO6 and PPARγ, thereby suppressing lipogenic gene transcription.

RESUMEN

BACKGROUND AND OBJECTIVE: Prospective sequential analyses after a new drug approval allow proactive surveillance of new drugs. In the current study, we demonstrate feasibility of frailty-specific sequential analyses for dabigatran, rivaroxaban, and apixaban versus warfarin. METHODS: We partitioned Medicare data from 2011 to 2020 into datasets based on calendar year following the date of drug approval. Each calendar year of data was added sequentially for analysis. We used a new-user, active comparative design by comparing the initiators of dabigatran versus warfarin, rivaroxaban versus warfarin, and apixaban versus warfarin. Patients aged ≥ 65 years with atrial fibrillation without contraindication to the anticoagulants were included. Claims-based frailty index ≥ 0.25 was used to define frailty. The initiators of each direct oral anticoagulant were propensity-score matched to the initiators of warfarin within each frailty status. The effectiveness outcome was ischemic stroke or systemic thromboembolism, and the safety outcome was major bleeding. For each calendar year, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards models using all data available up to that year. RESULTS: As an example of the results, in the 2020 dataset, compared with warfarin, apixaban was associated with a reduced risk of ischemic stroke or systemic thromboembolism (frail: HR 0.73, 95% CI 0.63-0.85; non-frail: HR 0.65, 95% CI 0.59-0.72) and major bleeding (frail: HR 0.63, 95% CI 0.57-0.69; non-frail: HR 0.59, 95% CI 0.56-0.63) in both frail and non-frail patients. We found evidence for apixaban's effectiveness and safety within 1-2 years after the drug approval in frail older patients. CONCLUSION: Our frailty-specific sequential analyses can be applied to future near-real-time monitoring of newly approved drugs.

RESUMEN

Malakoplakia is a rare chronic inflammatory disease that has been rarely reported in the genitourinary tract, gastrointestinal tract, adrenal glands, skin, lungs, bone, and endometrium. Central nervous system malakoplakia is extremely rare, and even then, it has only been reported in the cerebrum and cerebellum. A definite diagnosis of malakoplakia depends on microscopic detection of Michaelis-Gutmann bodies. We would like to present the case of a 61-year-old male who, after undergoing a liver transplant and receiving prolonged antibiotic treatment for Escherichia coli bacteremia, presented with quadriparesis and gait disturbance. The clinical and radiologic appearance of malakoplakia mimics that of malignant tumor. This is a condition with no established appropriate treatment and presents challenges due to its spinal cord location. However, this case presents a case of spinal cord malakoplakia and may provide newly differential diagnosis of an intramedullary mass in the spinal cord.

RESUMEN

This cross-sectional study evaluates the use of oral anticoagulants and antiplatelets, including aspirin, among nursing home residents with atrial fibrillation.

RESUMEN

BACKGROUND: Older adults with severe aortic stenosis (AS) may receive care in a nursing home (NH) prior to undergoing transcatheter aortic valve replacement (TAVR). NH level of care can be used to stabilize medical conditions, to provide rehabilitation services, or for long-term care services. Our primary objective is to determine whether NH utilization pre-TAVR can be used to stratify patients at risk for higher mortality and poor disposition outcomes at 30 and 365 days post-TAVR. METHODS: We conducted a retrospective cohort study among Medicare beneficiaries who spent ≥1 day in an NH 6 months before TAVR (2011-2019). The intensity of NH utilization was categorized as low users (1-30 days), medium users (31-89 days), long-stay NH residents (≥ 100 days, with no more than a 10-day gap in care), and high post-acute rehabilitation patients (≥90 days, with more than a 10-day gap in care). The probabilities of death and disposition were estimated using multinomial logistic regression, adjusting for age, sex, and race. RESULTS: Among 15,581 patients, 9908 (63.6%) were low users, 4312 (27.7%) were medium users, 663 (4.3%) were high post-acute care rehab users, and 698 (4.4%) were long-stay NH residents before TAVR. High post-acute care rehabilitation patients were more likely to have dementia, weight loss, falls, and extensive dependence of activities of daily living (ADLs) as compared with low NH users. Mortality was the greatest in high post-acute care rehab users: 5.5% at 30 days, and 36.4% at 365 days. In contrast, low NH users had similar mortality rates compared with long-stay NH residents: 4.8% versus 4.8% at 30 days, and 24.9% versus 27.0% at 365 days. CONCLUSION: Frequent bouts of post-acute rehabilitation before TAVR were associated with adverse outcomes, yet this metric may be helpful to determine which patients with severe AS could benefit from palliative and geriatric services.

RESUMEN

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson's disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function. METHODS: This is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging. DISCUSSION: The study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT06350617. Registered on 5 April 2024.

Asunto(s)

RESUMEN

OBJECTIVE: Previous research using the National Health and Aging Trends Study showed that a claims-based frailty index (CFI) could be useful for identifying moderate-to-severe dementia in Medicare claims data. This study aims to validate the findings in an independent cohort. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: The study included 658 fee-for-service beneficiaries with dementia who participated in the 2016-2020 Medicare Current Beneficiary Survey in the community-dwelling. METHODS: We operationalized the Functional Assessment Staging Test (FAST) scale (range: 1-7, stages 5-7 indicate moderate-to-severe dementia) using survey information. CFI (range: 0-1, higher scores indicate greater frailty) was calculated using Medicare claims 12 months before the participants' interview date. Using the previously proposed cut point of 0.280, we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying moderate-to-severe dementia. Survey procedures were used to account for survey design and weighted to reflect national estimates. RESULTS: The population had a mean age (SD) of 80.7 (8.9) years, 58.5% female, and 101 beneficiaries (14.8%) had moderate-to-severe dementia. The CFI cut point of 0.280 demonstrated sensitivity 0.49 (95% CI, 0.38-0.59), specificity 0.80 (0.77-0.84), PPV 0.30 (0.23-0.38), and NPV 0.90 (0.87-0.93). Compared with those with a CFI <0.280, beneficiaries with a CFI ≥0.280 had an elevated risk of mortality (2.9% vs 4.1%) over 1 year. CONCLUSIONS AND IMPLICATIONS: These results confirm our previous findings that CFI among beneficiaries with a dementia diagnosis is a useful measure of moderate-to-severe dementia for Medicare claims data.

RESUMEN

Endoplasmic reticulum (ER) stress is a major cause of hepatic steatosis through increasing de novo lipogenesis. Forkhead box O6 (FoxO6) is a transcription factor mediating insulin signaling to glucose and lipid metabolism. Therefore, dysregulated FoxO6 is involved in hepatic lipogenesis. This study elucidated the role of FoxO6 in ER stress-induced hepatic steatosis in vivo and in vitro. Hepatic ER stress responses and ß-oxidation were monitored in mice overexpressed with constitutively active FoxO6 allele and FoxO6-null mice. For the in vitro study, liver cells overexpressing constitutively active FoxO6 and FoxO6-siRNA were treated with high glucose, and lipid metabolism alterations were measured. ER stress-induced FoxO6 activation suppressed hepatic ß-oxidation in vivo. The expression and transcriptional activity of peroxisome proliferator-activated receptor α (PPARα) were significantly decreased in the constitutively active FoxO6 allele. Otherwise, inhibiting ß-oxidation genes were reduced in the FoxO6-siRNA and FoxO6-KO mice. Our data showed that the FoxO6-induced hepatic lipid accumulation was negatively regulated by insulin signaling. High glucose treatment as a hyperglycemia condition caused the expression of ER stress-inducible genes, which was deteriorated by FoxO6 activation in liver cells. However, high glucose-mediated ER stress suppressed ß-oxidation gene expression through interactions between PPARα and FoxO6 corresponding to findings in the in vivo study-lipid catabolism is also regulated by FoxO6. Furthermore, insulin resistance suppressed b-oxidation through the interaction between FoxO6 and PPARα promotes hepatic steatosis, which, due to hyperglycemia-induced ER stress, impairs insulin signaling. KEY MESSAGES: Our original aims were to delineate the interrelation between the regulation of PPARα and the transcription factor FoxO6 pathway in relation to lipid metabolism at molecular levels. Evidence on high glucose promoted FoxO6 activation induced lipid accumulation in liver cells. The effect of PPARα activation of the insulin signaling. FoxO6 plays a pivotal role in hepatic lipid accumulation through inactivation of PPARα in FoxO6-overexpression mice.

RESUMEN

Histone H3K9 methylated heterochromatin silences repetitive non-coding sequences and lineage-specific genes during development, but how tissue-specific genes escape from heterochromatin in differentiated cells is unclear. Here, we examine age-dependent transcriptomic profiling of terminally differentiated mouse retina to identify epigenetic regulators involved in heterochromatin reorganization. The single-cell RNA sequencing analysis reveals a gradual downregulation of Kdm3b in cone photoreceptors during aging. Disruption of Kdm3b (Kdm3b +/- ) of 12-month-old mouse retina leads to the decreasing number of cones via apoptosis, and it changes the morphology of cone ribbon synapses. Integration of the transcriptome with epigenomic analysis in Kdm3b +/- retinas demonstrates gains of heterochromatin features in synapse assembly and vesicle transport genes that are downregulated via the accumulation of H3K9me1/2. Contrarily, losses of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that the KDM3B-centered epigenomic network is crucial for balancing of cone photoreceptor homeostasis via the modulation of gene set-specific heterochromatin features during aging.

RESUMEN

Understanding patients' degree of frailty is crucial for tailoring clinical care for older adults based on their physiologic reserve and health needs ("frailty-guided clinical care"). Two prerequisites for frailty-guided clinical care are: (1) access to frailty information at the point of care and (2) evidence to inform decisions based on frailty information. Recent advancements include web-based frailty assessment tools and their electronic health records integration for time-efficient, standardized assessments in clinical practice. Additionally, database frailty scores from administrative claims and electronic health records data enable scalable assessments and evaluation of the effectiveness and safety of medical interventions across different frailty levels using real-world data. Given limited evidence from clinical trials, real-world database studies can complement trial results and help treatment decisions for individuals with frailty. This article, based on the Thomas and Catherine Yoshikawa Award lecture I gave at the American Geriatrics Society Annual Meeting in Long Beach, California, on May 5, 2023, outlines our group's contributions: (1) developing and integrating a frailty index calculator (Senior Health Calculator) into the electronic health records at an academic medical center; (2) developing a claims-based frailty index for Medicare claims; (3) applying this index to evaluate the effect of medical interventions for patients with and without frailty; and (4) efforts to disseminate frailty assessment tools through the launch of the eFrailty website and the forthcoming addition of the claims-based frailty index to the Centers for Medicare and Medicaid Services Chronic Conditions Data Warehouse. This article concludes with future directions for frailty-guided clinical care.

RESUMEN

OBJECTIVES: This study explores the evolving position of the health system chief information officer (CIO) by identifying new core roles for success. METHODS: An advisory board of industry executives and system leaders guided the study. Purposeful sampling was used to invite chief executive officer and CIOs from 65 not-for-profit US health systems to participate. Interviews were conducted with 51 executives from 33 different systems, using a comprehensive interview topic guide. Interview transcripts were analysed using NVivo software, focusing on themes related to the evolving role of the health system CIO. RESULTS: Analyses revealed three main themes, with the CIO as (1) enabler of strategic change and transformation, (2) strategic developer of technology and leadership talent and (3) driver of organisational culture. DISCUSSION: The role of CIO has undergone transformation from technology and information system management to strategic leadership within the broader health system context. It highlights the importance of comprehensive business knowledge for CIOs and the need for other C-suite executives to have a deeper understanding of information and technology. CONCLUSION: As healthcare continues to evolve, the role of the CIO is expected to expand further, requiring a blend of technical and strategic business skills. This evolution presents opportunities for health systems to enhance their leadership development programmes, preparing leaders for the complexities of the contemporary health system sector.

Asunto(s)

RESUMEN

Background: Coronavirus disease (COVID-19) may induce neurological issues, impacting brain structure and stroke recovery. Limited studies have explored its effects on post-stroke rehabilitation. Our study compares brain structure and connectivity, assessing rehabilitation outcomes based on pre-stroke COVID-19 infection. Methods: A retrospective analysis of 299 post-stroke rehabilitation cases from May 2021 to January 2023 included two groups: those diagnosed with COVID-19 at least two weeks before stroke onset (COVID group) and those without (control group). Criteria involved first unilateral supratentorial stroke, <3 months post-onset, initial MR imaging, and pre- and post-rehabilitation clinical assessments. Propensity score matching ensured age, sex, and initial clinical assessment similarities. Using lesion mapping, tract-based statistical analysis, and group-independent component analysis MRI scans were assessed for structural and functional differences. Results: After propensity score matching, 12 patients were included in each group. Patient demographics showed no significant differences. Analyses of MR imaging revealed no significant differences between COVID and control groups. Post-rehabilitation clinical assessments improved notably in both groups, however the intergroup analysis showed no significant difference. Conclusions: Previous COVID-19 infection did not affect brain structure or connectivity nor outcomes after rehabilitation.

RESUMEN

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) introduced chronic care management (CCM) services in 2015 for patients with multiple chronic diseases. Few studies examine the utilization of CCM services by geographic region, sociodemographic, and clinical characteristics. METHODS: We used 2014-2019 Medicare claims data from a 5% random sample of fee-for-service beneficiaries aged 65 years or over. We included beneficiaries potentially eligible for CCM services because they had multiple chronic conditions (1,073,729 in 2015 and 1,130,523 in 2019). We calculated the proportion of potentially eligible beneficiaries receiving CCM service each year for the total population and by geographic region, sociodemographic, and clinical characteristics. RESULTS: The proportion of beneficiaries with two or more chronic conditions receiving CCM services increased from 1.1% in 2015 to 3.4% in 2019. The increase in CCM use was higher in the southern region, among dually eligible beneficiaries and beneficiaries with a greater burden of chronic conditions (2-5 conditions vs ≥10 conditions: 0.7% vs 2.0% in 2015; 2.1% vs 7.0% in 2019) and frailty (robust vs severely frail: 0.6% vs 3.3% in 2015; 1.9% vs 9.4% in 2019). Nearly one out of five recipients did not continue CCM service after the initial service. CONCLUSION: We found that CCM service is being used by a very small fraction of eligible patients. Barriers and facilitators to more effective CCM adoption should be identified and incorporated into strategies that encourage more widespread use of this Medicare benefit.

Asunto(s)

RESUMEN

BACKGROUND: Ticagrelor is recommended over clopidogrel in acute coronary syndrome based on the results of the PLATO (Study of Platelet Inhibition and Patient Outcomes) trial. We aimed to emulate PLATO in older adults with and without frailty and with acute coronary syndrome treated with percutaneous coronary intervention. METHODS AND RESULTS: We created a new-user cohort of Medicare fee-for-service beneficiaries aged ≥65 years hospitalized for acute coronary syndrome from 2014 to 2018 and initiated ticagrelor or clopidogrel following percutaneous coronary intervention. Frailty was defined using a validated claims-based frailty index ≥0.25. Coprimary outcomes were major adverse cardiovascular events and major bleeding. Follow-up began on the date of first outpatient prescription for ticagrelor or clopidogrel and ended on the earliest date for an outcome event, death, discontinuation of the index drug, or disenrollment from Medicare. The study included 42 843 older adults; 23% were frail. After propensity score matching, the rates of major adverse cardiovascular events per 100 person-years comparing ticagrelor versus clopidogrel groups were 7.8 and 7.3 in the frail cohort (hazard ratio [HR], 1.07 [95% CI, 0.84-1.36]) and 3.7 and 4.2 in the nonfrail cohort (HR, 0.87 [95% CI, 0.75-1.02]). The corresponding rates of major bleeding were 4.3 and 3.8 in the frail cohort (HR, 1.12 95% CI, [0.80-1.56]) and 2.2 and 1.8 in the nonfrail cohort (HR, 1.22 [95% CI, 0.98-1.51]). CONCLUSIONS: There was a trend toward a modest reduction in risk of major adverse cardiovascular events and a trend toward a modest increase in risk of major bleeding with ticagrelor compared with clopidogrel in the nonfrail cohort. There was insufficient evidence for the benefit of ticagrelor in frail older adults.

Asunto(s)

RESUMEN

OBJECTIVE: Before 2019, the Minimum Data Set (MDS) and Outcome and Assessment Information Set (OASIS) had incongruent response categories for rating cognitive impairment and activities of daily living (ADLs), hindering direct comparisons between nursing facilities and home health. We devised rule-based algorithms to compare cognitive impairment and ADL limitations between these 2 care settings among people with Alzheimer's disease and Alzheimer's disease-related dementias (ADRD). DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Included fee-for-service Medicare beneficiaries (2013-2018) transitioning from nursing facilities to home health, with 1-year of continuous enrollment, aged ≥65 years, diagnosed ADRD, and with complete MDS discharge and OASIS admission assessments (N = 398,496). METHODS: We identified target phenotypes using the Cognitive Function Scale (CFS) and ADL items from the MDS discharge assessment as reference standards. We compared 6 OASIS-based algorithms for cognitive impairment and 1 for each ADL limitation by estimating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The average age was 83.5 (SD = 7.5) years and 82.3% transitioned from nursing to home health within 3 days. In the MDS discharge assessment, 42.2% had moderate-to-severe cognitive impairment. ADL limitations ranged from 71.4% for feeding to 97.8% for bathing. Compared with the moderate-to-severe cognitive impairment (CFS ≥3) on the MDS, the OASIS cognitive assessment indicating "considerable assistance to total dependence in routine situations" had 24% sensitivity, 94% specificity, 75% PPV, and 63% NPV. The ADL limitation algorithms exhibited high sensitivities (>96%) and PPVs (>94%) except for feeding (Sensitivity: 82%; PPV: 74%). Despite the short time frame between the 2 assessments, the OASIS admission assessment showed a higher prevalence of ADL limitations than the MDS discharge assessment. CONCLUSIONS AND IMPLICATIONS: We highlighted differences in patient function between post-acute care settings. Our algorithms can help researchers, clinicians, and policymakers standardize patient-centered outcomes for comparative effectiveness research or quality initiatives.

RESUMEN

Oridonin, a natural terpenoid isolated from the leaves of Isodon rubescens (Hemsley) H.Hara, is widely used in oriental medicine for its anticancer properties across various cancer types. Despite its prevalent use, the toxic effects of oridonin on male reproduction, particularly its impact on sperm functions and the mechanisms involved, are not well understood. This study aimed to explore the effects and underlying mechanisms of oridonin on sperm functions. We initially treated Duroc boar spermatozoa with varying concentrations of oridonin (0, 5, 50, 75, 100, and 150 µM) and incubated them to induce capacitation. We then assessed cell viability and several sperm functions, including sperm motility and motion kinematics, capacitation status, and ATP levels. We also analyzed the expression levels of proteins associated with the phosphatidylinositol 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (AKT) signaling pathway and phosphotyrosine proteins. Our results indicate that oridonin adversely affects most sperm functions in a dose-dependent manner. We observed significant decreases in AKT, p-AKT (Thr308), phosphatase and tensin homolog (PTEN), p-PDK1, and p-PI3K levels following oridonin treatment, alongside an abnormal increase in phosphotyrosine proteins. These findings suggest that oridonin may disrupt normal levels of tyrosine-phosphorylated proteins by inhibiting the PI3K/PDK1/AKT signaling pathway, which is crucial for cell proliferation, metabolism, and apoptosis, thus potentially harming sperm functions. Consequently, we recommend considering the reproductive toxicity of oridonin when using it as a therapeutic agent.

Asunto(s)