Risk Of Adverse Health Outcomes Research Articles

Cdon ablation in motor neurons causes age-related motor neuron degeneration and impaired sciatic nerve repair.

The functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging-related muscle wasting. Motor neuron diseases or aging-related muscle wasting in turn contribute to increased risk of adverse health outcomes in the elderly. Cdon (cell adhesion molecule-downregulated oncogene) belongs to the immunoglobulin superfamily of cell adhesion molecule and plays essential roles in multiple signalling pathways, including sonic hedgehog (Shh), netrin, and cadherin-mediated signalling. Cdon as a Shh coreceptor plays a critical role in motor neuron specification during embryonic development. However, its role in adult motor neuron function is unknown. Hb9-Cre recombinase-driven motor neuron-specific Cdon deficient mice (mnKO) and a compound mutant mice (mnKO::SOD1G93A ) were generated to investigate the role of Cdon in motor neuron degeneration. Motor neuron regeneration was examined by using a sciatic nerve crush injury model. To investigate the phenotype, physical activity, compound muscle action potential, immunostaining, and transmission electron microscopy were carried out. In the mechanism study, RNA sequencing and RNA/protein analyses were employed. Mice lacking Cdon in motor neurons exhibited middle age onset lethality and aging-related decline in motor function. In the sciatic nerve crush injury model, mnKO mice exhibited an impairment in motor function recovery evident by prolonged compound muscle action potential duration (4.63±0.35 vs. 3.93±0.22s for f/f, P<0.01) and physical activity. Consistently, neuromuscular junctions of mnKO muscles were incompletely occupied (49.79±5.74 vs. 79.39±3.77% fully occupied neuromuscular junctions for f/f, P<0.0001), suggesting an impaired reinnervation. The transmission electron microscopy analysis revealed that mnKO sciatic nerves had smaller axon diameter (0.88±0.13 vs. 1.43±0.48μm for f/f, P<0.0001) and myelination defects. RNA sequencing of mnKO lumbar spinal cords showed alteration in genes related to neurogenesis, inflammation and cell death. Among the altered genes, ErbB4 and FgfR expressions were significantly altered in mnKO as well as in Cdon-depleted NSC34 motor neuron cells. Consistently, Cdon-depleted NSC34 cells exhibited elevated levels of cleaved Caspase3 and γH2AX proteins, as well as Bax transcription. Cdon-depleted NSC34 cells also exhibited impaired activation of Akt in response to neuregulin-1 (NRG1) treatment. Our current data demonstrate the functional importance of Cdon in motor neuron function and nerve repair. Cdon ablation causes alterations in neurotrophin signalling that leads to motor neuron degeneration.

Exogenous corticosterone administration during pregnancy in mice alters placental and fetal thyroid hormone availability in females

IntroductionMaternal prenatal psychological stress is associated with adverse pregnancy outcomes and increased risk of adverse health outcomes in children. While the molecular mechanisms that govern these associations has not been fully teased apart, stress-induced changes in placental function can drive sex-specific phenotypes in offspring. We sought to identify and examine molecular pathways in the placenta that are altered in response to maternal prenatal stress. MethodsWe previously employed a mouse model of maternal prenatal stress where pregnant dams were treated with stress hormone (CORT) beginning in mid-gestation. Using this model, we conducted RNAseq analysis of whole placenta at E18.5. We used qRT-PCR to validate gene expression changes in the placenta and in a trophoblast cell line. ELISAs were used to measure the abundance of thyroid hormones in maternal and fetal serum and in the placenta. ResultsDio2 was amongst the top differentially expressed genes in response to exogenous stress hormone. Dio2 expression was more downregulated in placenta of female fetuses from CORT-treated dams than both control placenta from females and placenta from male fetuses. Consistent with Dio2's role in production of bioactive thyroid hormone (T3), we found that there was a reduction of T3 in placenta and serum of female embryos from CORT-treated dams at E18.5. Both T3 and T4 were reduced in the fetal compartment of the placenta of female fetuses from CORT-treated dams at E16.5. Exogenous stress hormone induced reduction in thyroid hormone in females was independent of circulating levels of TH in the dams. DiscussionThe placental thyroid hormone synthesis pathway may be a target of elevated maternal stress hormone and modulate fetal programming of health and disease of offspring in a sex-specific fashion.

Adverse Health Outcomes among Rural and Urban Breast Cancer Survivors: A Population-Based Cohort Study.

Limited population-based studies have focused on breast cancer survivors in rural populations. We sought to evaluate the risk of adverse health outcomes among rural and urban breast cancer survivors and to evaluate potential predictors for the highest risk outcomes. A population-based cohort of rural and urban breast cancer survivors diagnosed between 1997 and 2017 was identified in the Utah Cancer Registry (UCR). Rural breast cancer survivors were matched on year (±1 year) and age at cancer diagnosis (±1 year) with up to 5 urban breast cancer survivors (2,359 rural breast cancer survivors; 11,748 urban breast cancer survivors). Cox proportional hazards models were used to calculate HRs with 99% confidence intervals (CI) for adverse health outcomes overall, within 5 years, and >5 years after cancer diagnosis. Compared with urban breast cancer survivors, rural breast cancer survivors had a 39% (HR, 1.39; 95% CI, 1.02-1.65) higher risk of heart failure (HF) within the 5 years of follow-up. Overall, there was no increase in the risk of other evaluated adverse health outcomes. A higher baseline body mass index and Charlson Comorbidity Index, family history of cardiovascular diseases, family history of breast cancer, and advanced cancer stage were risk factors for HF for rural and urban breast cancer survivors, with similar levels of HF risk. Rural residence was associated with an increased risk of HF among breast cancer survivors. Our study highlights the need for primary preventive strategies for rural cancer survivors at risk of heart failure.

Combinations of Sarcopenia Diagnostic Criteria by Asian Working Group of Sarcopenia (AWGS) 2019 Guideline and Incident Adverse Health Outcomes in Community-Dwelling Older Adults.

This study aimed to investigate the association between combinations of sarcopenia criteria by the Asian Working Group of Sarcopenia (AWGS) 2019 guideline and incident adverse health outcomes. Longitudinal analyses of a cohort study. We conducted prospective 2-year follow-up analyses (N= 1959) among community-dwelling older adults enrolled in the nationwide Korean Frailty and Aging Cohort Study (KFACS). From the KFACS, 1959 older adults (52.8% women; mean age= 75.9 ± 3.9years) who underwent assessments for appendicular skeletal mass using dual-energy X-ray absorptiometry, handgrip strength, usual gait speed, 5-times sit-to-stand test, and Short Physical Performance Battery (SPPB) at baseline were included. Participants with each adverse health outcome [mobility disability, falls, and instrumental activities of daily living (IADL) disabilities] at baseline were excluded for each corresponding analysis. Multivariable logistic regression was performed to examine whether sarcopenia defined by different diagnostic criteria was associated with incident adverse health outcomes after 2 years. A total of 444 participants (22.7%) were diagnosed with sarcopenia as defined by AWGS 2019. In the multivariable analysis, sarcopenia defined as both low muscle mass and low physical performance increased the risk of mobility disability (OR 2.14, 95% CI 1.35-3.38) and falls (1.74, 95% CI 1.21-2.49). Only the criterion defined as both low muscle mass and physical performance using the SPPB increased the risk of falls with fracture (2.53, 95% CI 1.01-6.35) and IADL disabilities (2.77, 95% CI 1.21-6.33). However, sarcopenia defined as both low muscle mass and low hand grip strength showed no associations with the incidence of any of the adverse health outcomes. Our study suggests that the predictive value of adverse health outcomes for community-dwelling older adults is better when diagnosed with sarcopenia based on low muscle mass and physical performance. Furthermore, using the SPPB as a diagnostic tool for low physical performance may improve the predictive validity for falls with fracture and IADL disability. Our findings may be helpful for the early detection of individuals with sarcopenia who have a higher risk of adverse health outcomes.

Examining the Bidirectional Nature of Loneliness and Anxiety Among Older Adults in Daily Life.

Loneliness in later life increases the risk for adverse health outcomes; however, less is known about how loneliness is maintained. Anxiety may play an important role in maintaining loneliness, but little is known about how this connection plays out over time in daily life. This study thus focused on the within-person associations between momentary loneliness and anxiety among older adults. Participants were 317 diverse older adults (40% Black; 13% Hispanic, mean age = 77.45 years, 67% women) systematically recruited from the Bronx, NY, who completed ecological momentary assessments 5 times daily for 14 consecutive days. Multilevel models tested bidirectional contemporaneous, momentary cross-lagged (t - 1), day-level cross-lagged (average day to end of day), and day-to-day cross-lagged associations between loneliness and anxiety. Separate sensitivity analyses controlled for concurrent overall mood valence or depressed state. Gender and mild cognitive impairment (MCI) status were tested as moderators at all timescales. Significant bidirectional associations between loneliness and anxiety were found at the contemporaneous and momentary cross-lagged (t - 1) timescales. Higher average daily loneliness predicted higher end-of-day anxiety, but not vice versa. Loneliness and anxiety were not significantly associated from day to day. Sensitivity analyses revealed some associations varied depending on inclusion of either concurrent mood valence or depressed state. Neither gender nor MCI status moderated associations at any timescale. Findings shed light on the complex temporal ordering of loneliness and anxiety in daily life and extend contemporary theoretical notions of loneliness, including the possibility of interventions that target key moments in daily life.

Associations Between Dysphagia and Adverse Health Outcomes in Older Adults with Dementia in Intensive Care Units: A Retrospective Cohort Study.

Dysphagia is common in elderly patients with dementia and is one of the common clinical geriatric syndromes. It imposes a heavy burden on patients and their caregivers and is becoming an important public health problem. This study examined the association between dysphagia in older dementia patients in the ICU and the subsequent adverse health outcomes they experience. A retrospective analysis of adults (≥65 years) with dementia in ICUs of a Boston tertiary academic medical center was conducted. Using the International Classification of Diseases' Ninth and Tenth Revisions, dementia patients were identified. The study cohort comprised 1009 patients, median age 84.82 years, 56.6% female, predominantly White (72.9%). Patients were grouped based on swallowing function: dysphagia (n=282) and no-dysphagia (n=727). Dysphagia was identified via positive bedside swallowing screening. Primary outcomes were 90- and 180-day mortality, secondary outcomes included aspiration pneumonia, pressure injury, and delirium. Cohort characteristics were compared using the Wilcoxon rank-sum and chi-square tests. Dysphagia and outcomes correlations were examined via Kaplan-Meier survival analysis, Cox proportional-hazards regression models, logistic regression models, and subgroup analysis. After adjusting for covariates, the results from multivariate Cox proportional-hazards regression indicated that dysphagia was significantly associated with increased 90-day (HR=1.36, 95% CI=1.07-1.73, E-value=1.78) and 180-day (HR=1.47, 95% CI=1.18-1.82, E-value=1.94) mortality; the multifactorial logistic regression results indicated that dysphagia was associated with significant increases in pressure injury (OR=1.58, 95% CI=1.11-2.23, E-value=1.83) and aspiration pneumonia occurrence (OR=4.04, 95% CI=2.72-6.01, E-value=7.54), but was not significantly associated with delirium prevalence (OR=1.27, 95% CI=0.93-1.74). Dysphagia is likely to increase the risk of adverse health outcomes in older adults with dementia in ICU, and these adverse outcomes mostly include 90- and 180-day mortality, aspiration pneumonia, and pressure injury.

Trends in Illicit Cannabis Potency based on the Analysis of Law Enforcement Seizures in the Southern Area of Rome.

Cannabis remains the most illicitly produced and consumed substance worldwide, and the average trans-Δ9-tetrahydrocannabinol (THC) content in cannabis products (marijuana, hashish) has increased over time. This paper presents data about THC concentration in cannabis resin samples seized by law enforcement from 2015 to 2022 in the southern area of Rome (Italy). From 2015 to 2022, more than 1000 hashish samples were analyzed; the average THC content was 18.0% and dramatically increased from 13.7% (2015) to 27.1% (2022). The potency of THC in some samples characterized by unusual shape and color was higher than 24% and, in a few cases, higher than 40%. The age group most involved in seizures of cannabis resin concerned males aged between 15 and 36 years old. The spread of this phenomenon increases the risk of adverse health outcomes. Many observational studies compare the increased cannabis potency with the onset of psychosis, depression, anxiety and cannabis use disorders (CUDs), mainly in young adults. THC-potency monitoring provides data that can be helpful to create a network of communication and interaction between universities, and legislative and public health institutions to support education, awareness and surveillance related to cannabis abuse.

School-Based Versus Family-Based Interventions for the Reversal and Prevention of Obesity Among Hispanic Youth: a Review of the Literature.

Childhood obesity prevalence in the USA continues to rise and the Hispanic American population is disproportionately affected. Obesity prevalence among Hispanic youth is 26.2%, the highest prevalence of any minority or non-minority group of children. Prevalence of related conditions including type 2 diabetes, heart disease, and stroke also are increased among Hispanic Americans. Physicians and other providers commonly utilize body mass index (BMI) to estimate percentage of bodily fat and risk of adverse health outcomes. BMI has been shown to track from childhood to adulthood, demonstrating necessity for early intervention. Interventions targeting the prevention and reversal of obesity among children are categorized as school-based or family-based. Interventions vary but may involve strategies such as meetings to discuss health-related curriculum, augmentation of physical activity, and/or improvement of nutritional quality of food. The aim of this article is to review the current literature to determine whether family-based or school-based interventions are more successful in the prevention and reversal of obesity among Hispanic youth. We reviewed twenty-eight studies describing these interventions and included ten (four school-based and six family-based) in our in-depth analysis. Inclusion criteria required trials were conducted among adequate population sizes of Hispanic youth within the age range of interest, analyzed the primary outcome of interest, and took place after the year 2000. Family-based interventions typically involved small population sizes, were dependent upon parent adherence, and were rarely effective. School-based interventions were more commonly effective and involved larger population sizes, allowing for greater generalizability and greater impact of the intervention. Of five family or school-based interventions which successfully reduced BMI among this population, four included a component involving structured physical activity. School-based interventions involving augmentation of physical activity with minimal limitations of study execution demonstrated efficacy in the prevention and reversal of obesity among Hispanic children.

Chronic kidney disease: the missing concept in the 2019 EULAR/ERA-EDTA recommendations for lupus nephritis.

Chronic kidney disease (CKD) is diagnosed when glomerular filtration rate (GFR) falls below 60ml/min/1.73m2 or urinary albumin:creatinine ratio (UACR) reaches ≥30mg/g, as these two thresholds indicate a higher risk of adverse health outcomes, including cardiovascular mortality. CKD is classified as mild, moderate or severe, based on GFR and UACR values, and the latter two classifications convey a high or very high cardiovascular risk, respectively. Additionally, CKD can be diagnosed based on abnormalities detected by histology or imaging. Lupus nephritis (LN) is a cause of CKD. Despite the high cardiovascular mortality of patients with LN, neither albuminuria nor CKD are discussed in the 2019 European League Against Rheumatism (EULAR)/European Renal Association-European Dialysis and Transplant Association recommendations for the management of LN or the more recent 2022 EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases. Indeed, the proteinuria target values discussed in the recommendations may be present in patients with severe CKD and a very high cardiovascular risk who may benefit from guidance detailed in the 2021 European Society of Cardiology guidelines on cardiovascular disease prevention in clinical practice. We propose that the recommendations should move from a conceptual framework of LN as an entity separate from CKD to a framework in which LN is considered a cause of CKD and evidence generated from large CKD trials applies unless demonstrated otherwise.

Association between Rapid Eye Movement Obstructive Sleep Apnea and Metabolic Syndrome in a Japanese Population.

Objective Rapid eye movement (REM) obstructive sleep apnea (OSA) is characterized by apnea and hypopnea events due to airway collapse occurring predominantly or exclusively during REM sleep. OSA is a potential risk factor for metabolic dysfunction. However, the association between REM OSA and risk of adverse health outcomes remains unclear. The present study investigated the association between REM OSA and metabolic syndrome (MetS), including the MetS components of hypertension, dyslipidemia, and hyperglycemia, in the Japanese population. Methods In total, 836 Japanese patients with mild to moderate OSA were enrolled in this study. We compared the prevalence of MetS, including hypertension, dyslipidemia, and hyperglycemia, between REM OSA and non-REM OSA via univariate analyses of descriptive statistics and logistic regression analyses. Results The prevalence of hypertension was 68.3% in the REM OSA group and 56.6% in the non-REM OSA group (p<0.05). In addition, the prevalence of metabolic syndrome was significantly higher (37.0%) in the REM OSA group than in the non-REM-OSA group (25.2%). Logistic regression analyses showed that the prevalence of hypertension and Mets was significantly greater in the REM OSA group than in the non-REM-OSA group. Conclusion Our findings suggest that patients with REM OSA, regardless of age, sex, and body mass index, are at a higher risk of developing hypertension and MetS than patients with non-REM OSA.

Hospitalization and emergency department visits associated with potentially inappropriate medication in older adults: self-controlled case series analysis.

Potentially inappropriate medications (PIM) and resulting adverse health outcomes in older adults are a common occurrence. However, PIM prescriptions are still frequent for vulnerable older adults. Here, we sought to estimate the risk of hospitalization and emergency department (ED) visits associated with PIM prescriptions over different exposure periods and PIM drug categories. We used the National Health Insurance Service-Elderly Cohort Database (NHIS-ECDB) to construct the cohort and implemented a Self-Controlled Case Series (SCCS) method. Hospitalization or ED visits during the exposure and post-exposure periods were compared to those during the non-exposure period, and six PIM drug categories were evaluated. A conditional Poisson regression model was applied, and the risk of outcomes was presented as the incidence rate ratio (IRR). All potential time-varying covariates were adjusted by year. A total of 43,942 older adults aged ≥65 y who had at least one PIM prescription and the events of either hospitalization or ED visits between Jan 2016 and Dec 2019 were selected.. Mean days of each exposure period was 46 d (±123); risk was highest in exposure1 (1-7 d, 37.8%), whereas it was similar during exposure2 (15-28 d), and exposure3 (29-56 d) (16.6%). The mean number of total PIM drugs administered during the study period was 7.34 (±4.60). Both hospitalization and ED visits were significantly higher in both exposure (adjusted IRR 2.14, 95% Confidence Interval (CI):2.11-2.17) and post-exposure periods (adjusted IRR 1.41, 95% CI:1.38-1.44) in comparison to non-exposure period. The risk of adverse health outcomes was highest during the first exposure period (1-14 d), but decreased gradually over time. Among the PIM categories, pain medication was used the most, followed by anticholinergics. All PIM categories significantly increased the risk of hospitalization and ED visits, ranging from 1.18 (other PIM) to 2.85 (pain medication). Sensitivity analyses using the first incidence of PIM exposure demonstrated similar results. All PIM categories significantly increased the risk of hospitalization and ED visits, with the initial period of PIM prescriptions showing the highest risk. In subgroup analysis stratified by the number of medications, PIM effects on the risk of hospitalization and ED visits remained significant but gradually attenuated by the increased number of medications. Therefore, the development of deprescribing strategies to control PIM and polypharmacy collectively is urgent and essential.

Frailty detection in older adults via fractal analysis of acceleration signals from wrist-worn sensors

PurposeFrailty is a reversible multidimensional syndrome that puts older people at a high risk of adverse health outcomes. It has been proposed to emerge from the dysregulation of the complex system dynamics of physiologic control systems. We propose the analysis of the fractal complexity of hand movements as a new method to detect frailty in older adults.MethodsFRAIL scale and Fried’s phenotype scores were calculated for 1209 subjects—72.4 (5.2) y.o. 569 women—and 1279 subjects—72.6 (5.3) y.o. 604 women—in the pubicly available NHANES 2011–2014 data set, respectively. The fractal complexity of their hand movements was assessed with a detrended fluctuation analysis (DFA) of their accelerometry records and a logistic regression model for frailty detection was fit.ResultsGoodness-of-fit to a power law was excellent (R2>0.98\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{2}>0.98$$\\end{document}). The association between complexity loss and frailty level was significant, Kruskal–Wallis test (df = 2, Chisq = 27.545, p-value <0.001\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$<0.001$$\\end{document}). The AUC of the logistic classifier was moderate (AUC with complexity = 0.69 vs. AUC without complexity = 0.67).ConclusionFrailty can be characterized in this data set with the Fried phenotype. Non-dominant hand movements in free-living conditions are fractal processes regardless of age or frailty level and its complexity can be quantified with the exponent of a power law. Higher levels of complexity loss are associated with higher levels of frailty. This association is not strong enough to justify the use of complexity loss after adjusting for sex, age, and multimorbidity.

Home Noninvasive Ventilation for COPD.

Patients with hypercapnic COPD appear to represent a phenotype driven by specific physiology including air trapping and mechanical disadvantage, sleep hypoventilation, and sleep apnea. Such individuals appear to be at high risk for adverse health outcomes. Home noninvasive ventilation (NIV) has been shown to have the potential to help compensate for physiological issues underlying hypercapnia. In contrast to older literature, contemporary clinical trials of home NIV have been shown to improve patient-oriented outcomes including quality of life, hospitalizations, and mortality. Advancements in the use of NIV, including the use of higher inspiratory pressures, may account for recent success. Successful practical application of home NIV thus requires an adequate understanding of patient selection, devices and modes, and strategies for titration. The emergence of telemonitoring holds promise for further improvements in patient care by facilitating titration, promoting adherence, troubleshooting issues, and possibly predicting exacerbations. Given the complexity of home NIV, clinicians and health systems might consider establishment of dedicated home ventilation programs to provide such care. In addition, incorporation of respiratory therapist expertise is likely to improve success. Traditional fee-for-service structures have been a challenge for financing such programs, but ongoing changes toward value-based care are likely to make home NIV programs more feasible.

A Qualitative Exploration of Older Patients' Experiences With Frailty and Related Management Strategies.

Frailty is highly prevalent in hospitalized older patients and may increase the risk of adverse health outcomes. Understanding the experiences of older patients and the management strategies they use to recover from frailty is crucial to developing appropriate interventions. This study was designed to explore the frailty experiences of older adults and the management strategies they use to recover from frailty. Using purposive sampling, semistructured, face-to-face interviews were conducted with 16 older patients with frailty. Data were analyzed using content analysis. The experiences of participants were classified into three phases, including the (a) individual sensing phase, (b) daily-living-threatening phase, and (c) acclimatization and acceptance phase. When experiencing frailty, the participants developed management strategies to facilitate recovery, which manifested in three phases: (a) making flexible adjustments to the daily routine, (b) using adequate support systems, and (c) adopting positive thinking. The results indicate that familial support and positive thinking are important management strategies for successful recovery in frail individuals. Older patients require adequate support systems. Positive thinking was also found to be an effective management strategy for recovery. Healthcare professionals should not only focus on providing supportive resources but also provide support to older patients to facilitate their adoption of positive thinking to face life changes brought on by frailty.

1124-P: Outcomes of Health-Related Social Needs Screening in a Midwest Pediatric Diabetes Clinic Network

Background: Screening for health-related social needs (HRSNs) is recommended as part of standard diabetes care given the strong impact of social factors on health outcomes. We implemented a HRSN screen at routine diabetes clinic visits and assessed differences between youth with positive and negative screens. Methods: A 6-item questionnaire was adapted from the Accountable Health Communities Health-related Social Needs Screening Tool to screen for HRSNs in 4 domains: 1) housing, 2) utilities 3) transportation, 4) food. A positive screen was defined as any positive response to a HRSN. Cross-sectional data was analyzed using chi-square or independent t-test. Results: There were 4,119 screens completed over 14 months with 10% (n=438) being positive. The majority of positive screens were positive for a single HRSN (73%), most commonly food insecurity (66%). Table 1 compares youth with positive vs. negative screens. A higher percentage of positive screens was found in minority youth (p&amp;lt;0.001), while a lower percentage was seen in youth with commercial insurance (p&amp;lt;0.001) and diabetes technology use (p&amp;lt;0.001). Most indicators of diabetes control were less optimal in the positive screen group. Summary: Youth with HRSNs are at risk for adverse health outcomes. Screening for HRSNs can be incorporated into routine pediatric diabetes care and may help enhance health equity in delivery of care. Disclosure K.Halpin: None. J.D.Colvin: None. M.A.Clements: Consultant; Glooko, Inc., Research Support; Dexcom, Inc., Abbott Diabetes. E.L.Dewit: None. S.Relan: None. J.Roghair: None. R.Pomerantz: None. K.Evans: None. M.S.Barnes: None. H.Feingold: None. S.N.Jacob: None. C.Winterer: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Discrepancies between Cystatin C-Based and Creatinine-Based eGFR.

Recent guidance suggests clinicians increase use of cystatin C for the estimation of GFR. Discrepant levels of creatinine- versus cystatin C-based eGFR (eGFRcr versus eGFRcys) can occur and might signify inaccurate estimation of GFR using creatinine alone. This study sought to enhance the knowledge of the risk factors and clinical implications of having a large eGFR discrepancy. Participants in the Atherosclerosis Risk in Communities Study, a prospective cohort study of US adults, were followed over 25 years. eGFR discrepancy was measured at five clinical visits and defined as eGFRcys either 30% lower or higher than eGFRcr, the current clinical standard of care. The associations between eGFR discrepancies and kidney-related laboratory parameters were assessed using linear and logistic regression and long-term adverse outcomes, including kidney failure, AKI, heart failure, and death, using Cox proportional hazards models. Among 13,197 individuals (mean age 57 [SD 6] years, 56% women, 25% Black race), 7% had eGFRcys 30% lower than eGFRcr at visit 2 (1990-1992), and this proportion increased over time to 23% by visit 6 (2016-2017). By contrast, the percent with eGFRcys 30% higher than eGFRcr was relatively stable (3%-1%). Independent risk factors for having eGFRcys 30% lower than eGFRcr included older age, female sex, non-Black race, higher eGFRcr, higher body mass index, weight loss, and current smoking. Those with eGFRcys 30% lower than eGFRcr had more anemia and higher uric acid, fibroblast growth factor 23, and phosphate levels as well as higher risk of subsequent mortality, kidney failure, AKI, and heart failure compared with those with similar eGFRcr and eGFRcys values. Having eGFRcys lower than eGFRcr was associated with worse kidney-related laboratory derangements and a higher risk of adverse health outcomes. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000217.mp3.

Periodontal Disease and Other Adverse Health Outcomes Share Risk Factors, including Dietary Factors and Vitamin D Status.

For nearly a century, researchers have associated periodontal disease (PD) with risks of other adverse health outcomes such as cardiovascular disease, diabetes mellitus, and respiratory diseases, as well as adverse pregnancy outcomes. Those findings have led to the hypothesis that PD causes those adverse health outcomes either by increasing systemic inflammation or by the action of periodontopathic bacteria. However, experiments largely failed to support that hypothesis. Instead, the association is casual, not causal, and is due to shared underlying modifiable risk factors, including smoking, diet, obesity, low levels of physical activity, and low vitamin D status. Diabetes mellitus is also considered a risk factor for PD, whereas red and processed meat are the most important dietary risk factors for diabetes. Because PD generally develops before other adverse health outcomes, a diagnosis of PD can alert patients that they could reduce the risk of adverse health outcomes with lifestyle changes. In addition, type 2 diabetes mellitus can often be reversed rapidly by adopting an anti-inflammatory, nonhyperinsulinemic diet that emphasizes healthful, whole plant-based foods. This review describes the evidence that proinflammatory and prohyperinsulinemia diets and low vitamin D status are important risk factors for PD and other adverse health outcomes. We also make recommendations regarding dietary patterns, food groups, and serum 25-hydroxyvitamin D concentrations. Oral health professionals should routinely inform patients with PD that they could reduce their risk of severe PD as well as the risks of many other adverse health outcomes by making appropriate lifestyle changes.

Association between sarcopenia and frailty in elderly patients with chronic kidney disease.

Frailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non-dialysis patients. Therefore, this study aimed to determine frailty-associated factors in elderly CKD stage I-IV patients, expected to early identify and intervene in the frailty of elderly CKD patients. A total of 774 elderly CKD I-IV patients (>60years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty. Seven hundred seventy-four patients (median age 67years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8mL/min/1.73m2 . The prevalence of sarcopenia was 30.6%. The FI exhibited a right-skewed distribution. The age-related slope of FI was 1.4% per year on a logarithmic scale (r2 =0.706, 95% CI 0.9, 1.8, P<0.001). The upper limit of FI was around 0.43. The FI was related to mortality (HR=1.06, 95% CI 1.00, 1.12, P=0.041). Multivariate multinomial logistic regression analysis showed that sarcopenia, advanced age, CKD stage II-IV, low level of serum albumin and increased waist-hip ratio were significantly associated with high FI status, while advanced age and CKD stage III-IV were significantly associated with for median FI status. Moreover, the results from the subgroup were consistent with the leading results. Sarcopenia was independently associated with an increased risk for frailty in elderly CKD I-IV patients. Patients with sarcopenia, advanced age, high CKD stage, high waist-hip ratio and low serum albumin level should be assessed for frailty.

Patient “No-Show” Increases the Risk of 90-Day Complications Following Primary Total Knee Arthroplasty: A Retrospective Cohort Study of 6,776 Patients

BackgroundPatients who “no-show” (NS) clinical appointments are at a high risk of adverse health outcomes. The objective of this study was to evaluate and characterize the relationship between NS visits prior to primary total knee arthroplasty (TKA) and 90-day complications after TKA. MethodsWe retrospectively reviewed 6,776 consecutive patients undergoing primary TKA. Study groups were separated based on whether patients who NS versus always attended their appointment. A NS was defined as an intended appointment that was not canceled or rescheduled ≤2 hours before the appointment in which the patient did not show. Data collected included total number of follow-up appointments prior to surgery, patient demographics, comorbidities, and 90-day postoperative complications. ResultsPatients who have ≥3 NS appointments had 1.5 times increased odds of a surgical site infection (odds ratio (OR) 1.54, P = .002) compared to always attended patients. Patients who were ≤65 years old (OR: 1.41, P < .001), smokers (OR: 2.01, P < .001), and had a Charlson comorbidity index ≥3 (OR: 4.48, P < .001) were more likely to miss clinical appointments. ConclusionPatients who have ≥3 NS appointments prior to TKA had an increased risk for surgical site infection. Sociodemographic factors were associated with higher odds of missing a scheduled clinical appointment. These data suggest that orthopaedic surgeons should consider NS data as an important clinical decision-making tool to assess risk for postoperative complications to minimize complications following TKA.

Risk of incident melanoma among individuals with low-count monoclonal B-cell lymphocytosis (MBL).

7577 Background: Prior research has consistently shown that patients with chronic lymphocytic leukemia (CLL) have an ~2-fold increased risk of developing melanoma compared to controls. MBL is a common condition affecting 8-10 million adults over the age of 40 years in the United States and is a precursor to CLL. Little is known about the association between MBL and melanoma. Herein, we evaluated the risk of incident melanoma in a large cohort of individuals screened for MBL. Methods: Participants from the Mayo Clinic Biobank who had no prior history of hematologic malignancy, were 40 years or older, were residents of counties surrounding Mayo Clinic, and who provided blood samples between 7/2009 and 4/2022 were included in the study. Peripheral blood mononuclear cells were screened for MBL using highly sensitive eight-color flow cytometry. Individuals with MBL were classified as CLL-like MBL (CD5+, CD20dim) or atypical MBL (CD5+, CD20+) based on immunophenotypes, and also classified as low-count MBL (LCMBL) or high-count MBL (HCMBL) based on whether the percent clonal B-cell count was &lt; 85% or ≥85%, respectively. Diagnosis of melanoma was ascertained using ICD codes and review of the electronic health records. All individuals were followed from date of sample upon which MBL screening was performed to the earliest of incident melanoma, loss to follow-up, withdrawal from the study, or September 30, 2022. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for age, sex, and history of melanoma in previous 5 years. Results: A total of 7,334 participants were screened for MBL, of which 1,151 (16%) individuals had MBL. Among those with MBL, 1,107 (96.2%) had CLL-like MBL and 1098 (95.4%) had LC MBL. The median age at entry into the MBL screening cohort was 67 years (range 40-101) and 37% were male; individuals with MBL were older (median age 72 vs 65 years) and male (49% vs 35%). After a median follow-up of 2.9 years (range 0-13.2), 121 of the 7,334 (1.6%) participants developed incident melanoma after the date of MBL screening. The 10-year cumulative incidence of melanoma among individuals with MBL was 7.8% (95% CI 4.5-13.5%) compared to 3.4% (2.7-4.4%) in those who screened negative for MBL. After adjusting for age, sex, and history of prior melanoma, we found a 1.81-fold increased risk of incident melanoma (95% CI 1.19-2.76) among individuals with MBL. The increased risk of melanoma persisted when the analysis was restricted to individuals with LCMBL (HR = 1.84; 95% CI 1.21-2.82). Conclusions: In the largest MBL screening cohort to date, we found that LCMBL, a common condition, was associated with an 84% elevated risk of melanoma, similar to the ~2-fold increased risk observed in patients with CLL. These data, together with our prior findings of a heightened risk of serious infections and lymphoid malignancies, suggest that individuals with LCMBL are at increased risk for adverse health outcomes.