Vitamin D, Alzheimer's disease and related dementia.

Vitamin D has been proposed as a potential strategy to mitigate age-related cognitive decline and dementia, including Alzheimer's dementia, the predominant type of dementia. Rodent studies have provided insight into the potential mechanisms underlying the role of vitamin D in Alzheimer's disease and dementia. However, inconsistencies with respect to age, sex, and genetic background of the rodent models used poses some limitations regarding scientific rigor and translation. Several human observational studies have evaluated the association of vitamin D status with cognitive decline and dementia, and the results are conflicting. Randomized clinical trials of vitamin D supplementation have included cognitive outcomes. However, most of the available trials have not been designed specifically to test the effect of vitamin D on age-related cognitive decline and dementia, so it remains questionable how much additional vitamin D will improve cognitive performance. Here we evaluate the strengths and limitations of the available evidence regarding the role of vitamin D in AD, cognitive decline, dementia.

Comparison of Interventions for Lateral Elbow Tendinopathy: A Systematic Review and Network Meta-Analysis for Patient-Rated Tennis Elbow Evaluation Pain Outcome.

PURPOSE: There is controversy regarding the optimal treatment for lateral elbow tendinopathy (LET), and not all available treatment options have been compared directly with placebo/control. A network meta-analysis was conducted to compare the effectiveness of different LET treatments directly and indirectly against control/placebo based on a validated outcome, the Patient-Rated Tennis Elbow Evaluation (PRTEE) pain score. METHODS: Randomized, controlled trials comparing different treatment methods for LET were included, provided they reported outcome data using the PRTEE pain score. A network meta-analysis with random effect was used to combine direct and indirect evidence between treatments compared with placebo in the short term (up to six weeks) and midterm (more than six weeks and up to six months) after intervention. RESULTS: Thirteen studies with 12 comparators including control/placebo were eligible. The results indicated no significant improvement in PRTEE pain score in the short term across all treatments compared with control/placebo. In the midterm, physiotherapy/exercise showed benefit against placebo (mean difference: -4.32, 95% confidence interval: -7.58 and -1.07). Although steroid injections, dry needling, and autologous blood also exhibited potential treatment effects, it is crucial for the clinician to consider certain pitfalls when considering these treatments. The limited number of small studies and paucity of data call for caution in interpreting the results and need for further evidence. CONCLUSIONS: Patients should be informed that there is currently no strong evidence that any treatment produces more rapid improvement in pain symptoms when compared with control/placebo in the short and medium terms. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Matrix Gla protein and the long-term incidence and progression of coronary artery and aortic calcification in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Matrix Gla protein (MGP) is an inhibitor of calcification that requires carboxylation by vitamin K for activity. The inactive form of MGP, dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP), has been associated with increased calcification. However, it is not known whether there is a longitudinal relationship between dephosphorylated-uncarboxylated matrix Gla protein levels and coronary and aortic calcification in large population cohorts. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)]. RESULTS: For every one standard deviation (SD, 178 pmol/L) increment in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p < 0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p = 0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p < 0.001) AU/year. The association was stronger for DTAC in those ≥65 years and with diabetes. CONCLUSIONS: We found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature.

Perspective: Promoting Healthy Aging through Nutrition: A Research Centers Collaborative Network Workshop Report.

Within 20 y, the number of adults in the United States over the age of 65 y is expected to more than double and the number over age 85 y is expected to more than triple. The risk for most chronic diseases and disabilities increases with age, so this demographic shift carries significant implications for the individual, health care providers, and population health. Strategies that delay or prevent the onset of age-related diseases are becoming increasingly important. Although considerable progress has been made in understanding the contribution of nutrition to healthy aging, it has become increasingly apparent that much remains to be learned, especially because the aging process is highly variable. Most federal nutrition programs and nutrition research studies define all adults over age 65 y as "older" and do not account for physiological and metabolic changes that occur throughout older adulthood that influence nutritional needs. Moreover, the older adult population is becoming more racially and ethnically diverse, so cultural preferences and other social determinants of health need to be considered. The Research Centers Collaborative Network sponsored a 1.5-d multidisciplinary workshop that included sessions on dietary patterns in health and disease, timing and targeting interventions, and health disparities and the social context of diet and food choice. The agenda and presentations can be found at https://www.rccn-aging.org/nutrition-2023-rccn-workshop. Here we summarize the workshop's themes and discussions and highlight research gaps that if filled will considerably advance our understanding of the role of nutrition in healthy aging.

In-person peer support for critical care survivors: The ICU REcovery Solutions cO-Led through surVivor Engagement (ICURESOLVE) pilot randomised controlled trial.

BACKGROUND: Peer support is a promising intervention to mitigate post-ICU disability, however there is a paucity of rigorously designed studies. OBJECTIVES: The objective of this study was to establish feasibility of an in-person, co-designed, peer-support model. METHODS: Prospective, randomised, adaptive, single-centre pilot trial with blinded outcome assessment, conducted at a university-affiliated hospital in Melbourne, Australia. Intensive care unit survivors (and their nominated caregiver, where survivor and caregiver are referred to as a dyad), >18 years of age, able to speak and understand English and participate in phone surveys, were eligible. Participants were randomised to the peer-support model (six sessions, fortnightly) or usual care (no follow-up or targeted information). Two sequential models were piloted: 1. Early (2-3 weeks post hospital discharge) 2. Later (4-6 weeks post hospital discharge). Primary outcome was feasibility of implementation measured by recruitment, intervention attendance, and outcome completion. Secondary outcomes included post-traumatic stress and social support. RESULTS: Of the 231 eligible patients, 80 participants were recruited. In the early model we recruited 38 participants (28 patients, 10 carers; 18 singles, 10 dyads), with an average (standard deviation) age of 60 (18) years; 55 % were female. Twenty-two participants (58 %) were randomised to intervention. Participants in the early intervention model attended a median (interquartile range) of 0 (0-1) sessions (total 24 sessions), with 53% (n = 20) completing the main secondary outcome of interest (Impact of Event Scale) at the baseline and 37 % (n = 14) at the follow-up. For the later model we recruited 42 participants (32 patients, 10 carers; 22 singles, 10 dyads), with an average (standard deviation) age of 60.4 (15.4) years; 50 % were female. Twenty-one participants (50 %) were randomised to intervention. The later intervention model attended a median (interquartile range) of 1 (0-5) sessions (total: 44 sessions), with the main secondary outcome impact of events scale (IES-R) completed by 41 (98 %) participants at baseline and 29 (69 %) at follow-up. CONCLUSIONS: In this pilot trial, a peer-support model that required in-person attendance delivered in a later posthospital phase of recovery appeared more feasible than an early model. Further research should investigate alternative modes of intervention delivery to improve feasibility (ACTRN12621000737831).

PARC: a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of children and young adults.

Background: The survival for many children with relapsed/refractory cancers remains poor despite advances in therapies. Arginine metabolism plays a key role in the pathophysiology of a number of pediatric cancers. We report the first in child study of a recombinant human arginase, BCT-100, in children with relapsed/refractory hematological, solid or CNS cancers. Procedure: PARC was a single arm, Phase I/II, international, open label study. BCT-100 was given intravenously over one hour at weekly intervals. The Phase I section utilized a modified 3 + 3 design where escalation/de-escalation was based on both the safety profile and the complete depletion of arginine (defined as adequate arginine depletion; AAD <8µM arginine in the blood after 4 doses of BCT-100). The Phase II section was designed to further evaluate the clinical activity of BCT-100 at the pediatric RP2D determined in the Phase I section, by recruitment of patients with pediatric cancers into 4 individual groups. A primary evaluation of response was conducted at eight weeks with patients continuing to receive treatment until disease progression or unacceptable toxicity. Results: 49 children were recruited globally. The Phase I cohort of the trial established the Recommended Phase II Dose of 1600U/kg iv weekly in children, matching that of adults. BCT-100 was very well tolerated. No responses defined as a CR, CRi or PR were seen in any cohort within the defined 8 week primary evaluation period. However a number of these relapsed/refractory patients experienced prolonged radiological SD. Conclusion: Arginine depletion is a clinically safe and achievable strategy in children with cancer. The RP2D of BCT-100 in children with relapsed/refractory cancers is established at 1600U/kg intravenously weekly and can lead to sustained disease stability in this hard to treat population. Clinical trial registration: EudraCT, 2017-002762-44; ISRCTN, 21727048; and ClinicalTrials.gov, NCT03455140.

Associations of inflammatory and metabolic biomarkers with incident erosive hand osteoarthritis in the osteoarthritis initiative cohort.

OBJECTIVE: Erosive hand osteoarthritis (eHOA) is a subtype of hand osteoarthritis (OA) that develops in finger joints with pre-existing OA and is differentiated by clinical characteristics (hand pain/disability, inflammation, and erosions) that suggest inflammatory or metabolic processes. METHOD: This was a longitudinal nested case-cohort design among Osteoarthritis Initiative participants who had hand radiographs at baseline and 48-months, and biospecimens collected at baseline. We classified incident radiographic eHOA in individuals with ≥1 joint with Kellgren-Lawrence ≥2 and a central erosion present at 48-months but not at baseline. We used a random representative sample (n = 1282) for comparison. We measured serum biomarkers of inflammation, insulin resistance and dysglycemia, and adipokines using immunoassays and enzymatic colorimetric procedures, blinded to case status. RESULTS: Eighty-six participants developed incident radiographic eHOA. In the multivariate analyses adjusted for age, gender, race, smoking, and body mass index, and after adjustment for multiple analyses, incident radiographic eHOA was associated with elevated levels of interleukin-7 (risk ratio (RR) per SD = 1.30 [95% confidence interval (CI) 1.09, 1.55] p trend 0.01). CONCLUSION: This exploratory study suggests an association of elevated interleukin-7, an inflammatory cytokine, with incident eHOA, while other cytokines or biomarkers of metabolic inflammation were not associated. Interleukin-7 may mediate inflammation and tissue damage in susceptible osteoarthritic finger joints and participate in erosive progression.

Effects of long-term high dose aspartame on body mass, bone strength, femoral geometry, and microbiota composition in a young and aged cohort of male and female mice.

Background: Recent reassessment of the safety of aspartame has prompted increased evaluation of its effect on the health of a range of tissues. The gut microbiome is altered by oral aspartame. One prior study suggested that changes in the microbiome caused by aspartame could influence the strength of bone in young skeletally developing mice. Here we ask how aspartame influences bone in mice of different age and sex. Objective: The objective of this study was to determine the effect of aspartame on the bone strength and gut microbiota of young and aged mice. Methods: Male and female C57Bl/6J mice were untreated or treated with a high dose of aspartame in their drinking water from 1 month of age until 4 (young cohort; n = 80) or 22 months (aged cohort; n = 52). Results: In aged males, mice treated with aspartame had greater body mass, whole bone strength, and femoral geometry relative to untreated. Specifically, in aged males, aspartame led to 9% increase in body mass (p < 0.001), 22% increase in whole bone strength (p = 0.006), and 17% increase in section modulus (p < 0.001) relative to untreated mice. Aged males and females receiving aspartame had a different microbiota than untreated mice and a decreased abundance of Odoribacter. No differences in body mass, whole bone strength, or femoral geometry were associated with aspartame dosing in young males or young or aged females. Conclusions: Aspartame treated aged males had greater whole bone strength and the effect appeared to be explained by greater body mass. Aspartame treatment did not alter whole bone strength in young males or young or aged females despite the aspartame having a similar effect on the microbiota of both aged males and females.

Symptoms and signs in patients with heart failure: association with 3-month hospitalisation and mortality.

OBJECTIVES: To determine the association between symptoms and signs reported in primary care consultations following a new diagnosis of heart failure (HF), and 3-month hospitalisation and mortality. DESIGN: Nested case-control study with density-based sampling. SETTING: Clinical Practice Research Datalink, linked to hospitalisation and mortality (1998-2020). PARTICIPANTS: Database cohort of 86 882 patients with a new HF diagnosis. In two separate analyses for (1) first hospitalisation and (2) death, we compared the 3-month history of symptoms and signs in cases (patients with HF with the event), with their respective controls (patients with HF without the respective event, matched on diagnosis date (±1 month) and follow-up time). Controls could be included more than once and later become a case. MAIN OUTCOME MEASURES: All-cause, HF and non-cardiovascular disease (non-CVD) hospitalisation and mortality. RESULTS: During a median follow-up of 3.22 years (IQR: 0.59-8.18), 56 677 (65%) experienced first hospitalisation and 48 146 (55%) died. These cases were matched to 356 714 and 316 810 HF controls, respectively. For HF hospitalisation, the strongest adjusted associations were for symptoms and signs of fluid overload: pulmonary oedema (adjusted OR 3.08; 95% CI 2.52, 3.64), shortness of breath (2.94; 2.77, 3.11) and peripheral oedema (2.16; 2.00, 2.32). Generic symptoms also showed significant associations: depression (1.50; 1.18, 1.82), anxiety (1.35; 1.06, 1.64) and pain (1.19; 1.10, 1.28). Non-CVD hospitalisation had the strongest associations with chest pain (2.93; 2.77, 3.09), fatigue (1.87; 1.73, 2.01), general pain (1.87; 1.81, 1.93) and depression (1.59; 1.44, 1.74). CONCLUSIONS: In the primary care HF population, routinely recorded cardiac and non-specific symptoms showed differential risk associations with hospitalisation and mortality.

Dietary Intakes of Community-Dwelling Adults in the United States across Older Adulthood: National Health and Nutrition Examination Survey 2015-March 2020.

BACKGROUND: Dietary guidance is set on the basis of age and life stage and defines older adults as ≥60 y. Yet, little is known about if and/or how diet quality differs beyond the age of 60. OBJECTIVE: The objective of this study was to compare the dietary intakes of 60-69 (n = 2079), 70-79 (n = 1181), and 80+ y old (n = 644) noninstitutionalized men and women in the United States using the Healthy Eating Index 2015 (HEI) and the What We Eat in America food categories. METHODS: Data were obtained from National Health and Nutrition Examination Survey 2015-2016 and 2017-March 2020. HEI and component scores were calculated using the population ratio method. Population estimates for dietary intake were calculated as the average reported over 2 separate nonconsecutive 24-h dietary recalls. RESULTS: In men and women, the reported energy intake was lower among the 80+ y olds (kcal/d men-80+: 1884 ± 30, 70-79: 2022 ± 33, 60-69: 2142 ± 39; women-80+: 1523 ± 36; 70-79: 1525 ± 33, 60-69: 1650 ± 25; P-trend < 0.001). Total HEI scores did not differ significantly across the 3 age categories, but the 80+ y olds had significantly lower scores for the green vegetables and beans component than the 60-69 y olds [men-mean (95% confidence interval): 2.0 (1.5, 2.5) compared with 3.4 (2.6, 4.1); women-2.3 (1.8, 2.8) compared with 4.4 (3.7, 5.0)]. In women, the percentage of daily calories from protein was significantly lower in the 80+ y olds than in the 60-69 and 70-79 y olds (12.9% ± 0.6%, compared with 17.0% ± 0.9% and 15.6% ± 0.6%, respectively). Protein intake did not differ significantly among the 3 age groups in men. The 80+ y old men and women reported consuming a significantly higher percentage of calories from snacks and sweets compared with the 60-69 y olds (men-80+: 18.1% ± 0.8%, 60-69: 15.4% ± 0.7%; women-80+: 19.6% ± 0.8%, 60-69: 15.5% ± 0.7%). CONCLUSION: The diet of 80+ y olds differed from that of 60-69 y olds in some key components, including energy, snacks and sweets, protein, and green vegetables. Future research is needed to determine if there are health-related consequences to these differences.

Using the kidney failure risk equation to predict end-stage kidney disease in CKD patients of South Asian ethnicity: an external validation study.

BACKGROUND: The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors - age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death. METHODS: Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care. RESULTS: The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care. CONCLUSIONS: The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.

Incorporation of patient and public involvement in statistical methodology research: a survey assessing current practices and attitudes of researchers.

BACKGROUND: Patient and public involvement (PPI) ensures that research is designed and conducted in a manner that is most beneficial to the individuals whom it will impact. It has an undisputed place in applied research and is required by many funding bodies. However, PPI in statistical methodology research is more challenging and work is needed to identify where and how patients and the public can meaningfully input in this area. METHODS: A descriptive cross-sectional research study was conducted using an online questionnaire, which asked statistical methodologists about themselves and their experience conducting PPI, either to inform a grant application or during a funded statistical methodology project. The survey included both closed-text responses, which were reported using summary statistics, and open-ended questions for which common themes were identified. RESULTS: 119 complete responses were recorded. Individuals who completed the survey displayed an even range of ages, career lengths and positions, with the majority working in academia. 40.3% of participants reported undertaking PPI to inform a grant application and the majority reported that the inclusion of PPI was received positively by the funder. Only 21.0% of participants reported undertaking PPI during a methodological project. 31.0% of individuals thought that PPI was "very" or "extremely" relevant to statistical methodology research, with 45.5% responding "somewhat" and 24.4% answering "not at all" or "not very". Arguments for including PPI were that it can provide the motivation for research and shape the research question. Negative opinions included that it is too technical for the public to understand, so they cannot have a meaningful impact. CONCLUSIONS: This survey found that the views of statistical methodologists on the inclusion of PPI in their research are varied, with some individuals having particularly strong opinions, both positive and negative. Whilst this is clearly a divisive topic, one commonly identified theme was that many researchers are willing to try and incorporate meaningful PPI into their research but would feel more confident if they had access to resources such as specialised training, guidelines, and case studies.

Patient and public involvement (or PPI) means researchers working in partnership with patients and the public in any part of research. It can include helping decide what the research question is, how to pass on results to the public, and telling researchers what areas are most important to patients and the public. Statistical methods are the tools we use to analyse data. Statistical methodology research involves making sure these tools use our healthcare data in the best way. PPI is essential in health research and is becoming more common in statistical methodology research. But it can be hard to know how to include patients and the public in statistical methodology research. It may seem complex and not directly related to patients. This paper describes the results from a survey we did about the experiences of researchers who have carried out PPI for statistical methodology research. We asked them what they think about it, and how it affects their research. We also asked if they feel confident including PPI in their research, and whether they are given enough help. Researchers had different views about PPI for statistical methodology research. Some people thought PPI was very important in their research, but others weren't sure. Many people said that they would like more help such as training and guidelines to help them do better PPI in the future.

Worsening psychological wellbeing of Australian hospital clinical staff during three waves of the coronavirus (COVID-19) pandemic.

Objective This study aimed to assess and compare the psychological wellbeing of Australian hospital clinical staff at three timepoints during the coronavirus disease 2019 (COVID-19) pandemic. Methods An anonymous, online, cross-sectional survey was conducted at three timepoints during the COVID-19 pandemic (T1: May-June 2020; T2: October-December 2020; T3: November 2021-January 2022). The surveys were completed by nurses, midwives, doctors and allied health staff employed at a large metropolitan tertiary health service located in Melbourne, Australia. The Depression, Anxiety and Stress Scale (DASS-21) assessed respondents' psychological wellbeing in the past week. General linear models were used to measure the effects of survey timepoint on DASS-21 subscale scores, adjusting for selected sociodemographic and health characteristics. Results A total of 1470 hospital clinical staff completed at least one survey (T1: 668 (14.7%), T2: 358 (7.9%) and T3: 444 (9.8%)). Respondents' sociodemographic characteristics were similar across the three timepoints and within professional discipline groups. Respondents' psychological wellbeing was worse at T3 compared to the earlier survey timepoints. Adjusting for respondent characteristics, depression, anxiety and stress scores were significantly higher for respondents of the third survey compared to the first (P < 0.001). Conclusions There was a significant and persistent negative impact on the psychological wellbeing of hospital clinical staff in Australia across waves of the COVID-19 pandemic. Hospital clinical staff would benefit from ongoing and continued wellbeing support during and after pandemic waves.

Using temporal recalibration to improve the calibration of risk prediction models in competing risk settings when there are trends in survival over time.

We have previously proposed temporal recalibration to account for trends in survival over time to improve the calibration of predictions from prognostic models for new patients. This involves first estimating the predictor effects using data from all individuals (full dataset) and then re-estimating the baseline using a subset of the most recent data whilst constraining the predictor effects to remain the same. In this article, we demonstrate how temporal recalibration can be applied in competing risk settings by recalibrating each cause-specific (or subdistribution) hazard model separately. We illustrate this using an example of colon cancer survival with data from the Surveillance Epidemiology and End Results (SEER) program. Data from patients diagnosed in 1995-2004 were used to fit two models for deaths due to colon cancer and other causes respectively. We discuss considerations that need to be made in order to apply temporal recalibration such as the choice of data used in the recalibration step. We also demonstrate how to assess the calibration of these models in new data for patients diagnosed subsequently in 2005. Comparison was made to a standard analysis (when improvements over time are not taken into account) and a period analysis which is similar to temporal recalibration but differs in the data used to estimate the predictor effects. The 10-year calibration plots demonstrated that using the standard approach over-estimated the risk of death due to colon cancer and the total risk of death and that calibration was improved using temporal recalibration or period analysis.

Outcomes of chest drain management using only air leak (without fluid) criteria for removal after general thoracic surgery-a drainology study.

Background: Chest drain management is a variable aspect of postoperative care in thoracic surgery, with different opinion for air and drain volume output. We aim to study if acceptable safety was maintained using air leak criteria alone. Methods: A 9-year retrospective analysis of protocolised chest drain management using digital drain air leak cut off less than 20 mL/min for more than 6 h for drain removal in patients undergoing general thoracic surgery. We excluded patients if a chest drain was not required nor removed during admission or if patients underwent volume reduction or pneumonectomy. Withdrawal criteria were suspected bleeding or chylothorax. Postoperative films were reviewed to document post-drain removal pneumothorax, pleural effusion, and reintervention (drain re-insertion). Results: Between 2012 and 2021, 1,187 patients had thoracic surgery under a single surgeon. Following exclusion and withdrawal criteria, 797 patients were left for analysis. The mean age [standard deviation (SD)] was 61 [16] years and 383 (48%) were male. Median [interquartile range (IQR)] duration of drain insertion was 1 [1-2] day with a median length of hospital stay of 4 [2-6] days. Post-drain removal pneumothorax was observed in 141 (17.7%), post-drain removal pleural effusion was observed in 75 (9.4%) and re-intervention (reinsertion of chest drain) required in 17 (2.1%). Conclusions: Our results demonstrate acceptable levels of safety using digital assessment of air leak as the sole criteria for drain removal in selected patients after general thoracic surgery.

Lack of Consensus Between Measurements of Plasma Phylloquinone by Enzyme-Linked Immunosorbent assays and a Well-Validated High-Performance Liquid Chromatographic Method.

Enzyme-linked i2mmunosorbent assays (ELISAs) that measure circulating phylloquinone have become commercially available, but their validity is uncertain. The objective of this study was to compare plasma phylloquinone concentrations measured using two commercially available ELISAs with concentrations measured using a validated high-performance liquid chromatography (HPLC) assay in 108 samples obtained from participants in a depletion (∼10 mcg phylloquinone/d)-supplementation (∼500 mcg phylloquinone/d) study. The geometric mean of plasma phylloquinone measured with ELISA A was 0.70 nmol/L, 37% lower than that measured with HPLC. The mean of the ELISA B measures was 12.4 nmol/L, >700% higher than the HPLC measures. Plasma phylloquinone measured using HPLC was significantly lower during phylloquinone depletion than supplementation (0.4 ± 0.1 compared with 1.2 ± 0.2 nmol/L; P < 0.001). Neither of the two ELISAs detected any significant difference in plasma phylloquinone concentrations between depletion and supplementation (ELISA A, P = 0.76; ELISA B, P = 0.29). These findings reinforce the need to validate plasma phylloquinone assays as they become available. Curr Dev Nutr 2023;x:xx.

Association of Vitamin K Status with Arterial Calcification and Stiffness in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort.

Background: Arterial calcification and stiffness are common in people with chronic kidney disease (CKD). Higher vitamin K status has been associated with less arterial calcification and stiffness in CKD in cross-sectional studies. Objectives: To determine the association of vitamin K status with coronary artery calcium (CAC) and arterial stiffness [pulse wave velocity (PWV)] at baseline and over 2-4 follow-up years in adults with mild-to-moderate CKD. Methods: Participants (n = 2722) were drawn from the well-characterized Chronic Renal Insufficiency Cohort. Two vitamin K status biomarkers, plasma phylloquinone and plasma dephospho-uncarboxylated matrix gla protein [(dp)ucMGP], were measured at baseline. CAC and PWV were measured at baseline and over 2-4 y of follow-up. Differences across vitamin K status categories in CAC prevalence, incidence, and progression (defined as ≥100 Agatston units/y increase) and PWV at baseline and over follow-up were evaluated using multivariable-adjusted generalized linear models. Results: CAC prevalence, incidence, and progression did not differ across plasma phylloquinone categories. Moreover, CAC prevalence and incidence did not differ according to plasma (dp)ucMGP concentration. Compared with participants with the highest (dp)ucMGP (≥450 pmol/L), those in the middle category (300-449 pmol/L) had a 49% lower rate of CAC progression (incidence rate ratio: 0.51; 95% CI: 0.33, 0.78). However, CAC progression did not differ between those with the lowest (<300 pmol/L) and those with the highest plasma (dp)ucMGP concentration (incidence rate ratio: 0.82; 95% CI: 0.56, 1.19). Neither vitamin K status biomarker was associated with PWV at baseline or longitudinally. Conclusions: Vitamin K status was not consistently associated with CAC or PWV in adults with mild-to-moderate CKD.

Chow diet in mouse aging studies: nothing regular about it.

Chow diet is used in the majority of rodent studies and, although assumed to be standardized for dietary source and nutritional contents, it varies widely across commercial formulations. Similarly, current approaches to study aging in rodents involve a single-diet formulation across the lifespan and overlook age-specific nutritional requirements, which may have long-term effects on aging processes. Together, these nutrition-based disparities represent major gaps in geroscience research, affecting the interpretation and reproducibility of the studies. This perspective aims to raise awareness on the importance of rodent diet formulation and proposes that geroscientists include detailed descriptions of all experimental diets and feeding protocols. Detailed reporting of diets will enhance rigor and reproducibility of aging rodent studies and lead to more translational outcomes in geroscience research.