Predictors of Prolonged Length of Stay after Elective Carotid Revascularization.

OBJECTIVE: Postoperative day-one discharge is used as a quality-of-care indicator after carotid revascularization. This study identifies predictors of prolonged length of stay (pLOS), defined as a postprocedural LOS of > 1 day, after elective carotid revascularization. METHODS: Patients undergoing carotid endarterectomy (CEA), Transcarotid artery revascularization (TCAR) and Transfemoral carotid artery stenting (TFCAS) in the Vascular Quality Initiative between 2016 and 2022 were included in this analysis. Multivariable logistic regression analysis was used to identify predictors of pLOS, defined as a postprocedural LOS of > 1 day, after each procedure. RESULTS: A total of 118,625 elective cases were included. pLOS was observed in nearly 23.2% of patients undergoing carotid revascularization. Major adverse events, including neurological, cardiac, infectious, and bleeding complications, occurred in 5.2% of patients and were the most significant contributor to pLOS after the 3 procedures. Age, female sex, nonwhite race, insurance status, high comorbidity index, prior ipsilateral CEA, non-ambulatory status, symptomatic presentation, surgeries occurring on Friday and postoperative hypo- or hypertension were significantly associated with pLOS across all 3 procedures. For CEA, additional predictors included contralateral carotid artery occlusion, preoperative use of dual antiplatelets and anticoagulation, low physician volume (< 11 cases/year) and drain use. For TCAR, preoperative anticoagulation use, low physician case volume (<6 cases/year), no protamine use, and post-stent dilatation intraoperatively were associated with pLOS. One-year analysis showed a significant association between pLOS and increased mortality for all 3 procedures; CEA (HR,1.64; 95%CI, 1.49-1.82), TCAR (HR,1.56; 95%CI, 1.35-1.80), and TFCAS (HR,1.33; 95%CI,1.08-1.64) (all P<0.05). CONCLUSIONS: A postoperative LOS of more than 1 day is not uncommon after carotid revascularization. Procedure-related complications are the most common drivers of pLOS. Identifying patients are risk for pLOS highlight quality improvement strategies that can optimize short and 1-year outcomes of patients undergoing carotid revascularization.

How do transfusion services manage patients taking therapies such as anti-CD38 and anti-CD47 known to interfere with red blood cell compatibility testing?

BACKGROUND: Drugs such as daratumumab (Darzalex, anti-CD38) and Hu5F9-G4 (magrolimab, anti-CD47) may interfere with red blood cell compatibility testing as CD38 and CD47 are expressed on red blood cells. STUDY DESIGN AND METHODS: A survey of AABB member transfusion services was undertaken to understand their experiences of managing patients taking therapeutic monoclonal antibodies that are known to interfere with blood grouping and compatibility testing. RESULTS: The survey was distributed to the contact person at US-based AABB member transfusion services. The response rate was 27%. 172 of 240 (72%) indicated they had difficulties in performing compatibility testing in patients taking daratumumab and 66 of 91 (73%) reported difficulties in performing compatibility testing in patients taking magrolimab. Actions taken to provide compatible blood for these patients included referral of all samples to a reference center, blood group pheno/genotyping the patient in advance of starting the drug, treating reagent cells with 0.2 M dithiothreitol and using K-negative red cell units for patients taking daratumumab, and Gamma-clone (Immucor) anti-IgG for indirect antiglobulin testing for patients taking magrolimab. Lack of communication from clinical services about drug treatment was identified as a concern. CONCLUSION: The results of the survey demonstrate that transfusion services are having challenges with the transfusion management of patients taking therapeutic monoclonal antibodies, and further education is needed.

Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart.

Elevated intracellular sodium Nai adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Nai decreases Gibb's free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH2, which are all reversed on lowering Nai to baseline levels. Pseudo hypoxia and stabilization of HIF-1α is observed despite normal tissue oxygenation. Inhibition of mitochondrial Na/Ca-exchange with CGP-37517 or treatment with the mitochondrial ROS scavenger MitoQ prevents the metabolic alterations during Nai elevation. Elevated Nai plays a reversible role in the metabolic and functional changes and is a novel therapeutic target to correct metabolic dysfunction in heart failure.

Opportunities to improve feedback to reduce blood component wastage: Results of a national scheme evaluation.

BACKGROUND: Blood components are costly and scarce. The Blood Stocks Management Scheme (BSMS) was established in the United Kingdom (UK) to support hospital transfusion services and national blood services through collection, analysis, and monthly feedback of data on blood component inventory and wastage management. There is a growing evidence base on how best to deliver feedback for quality improvement. We assessed the quality and utility of the monthly BSMS component reports. METHODS: We assessed the content of BSMS reports issued in March 2023 against established criteria for effective feedback. Two researchers independently rated whether criteria spanning the five domains of goal setting, data collection, feedback content, feedback display and feedback delivery were fully, partially or not met. Disagreements were resolved through discussion. We conducted an online questionnaire survey of recipients of BSMS reports during March 2023 to assess their use of reports and seek suggestions for improvement. RESULTS: Five out of 20 criteria for effective feedback were fully met. Areas for improvement included placing more emphasis in the feedback on positive change, linking data and summary messages, and including specific suggestions for action. Respondents highlighted the value of benchmarked comparisons with other hospital transfusion services. CONCLUSION: There is scope for enhancing the effectiveness and utility of BSMS feedback reports and hence reducing wastage of blood components. This methodology for evaluation of feedback could be utilized to improve other areas of transfusion practice.

Peak alpha frequency and electroencephalographic microstates are correlated with aggression in schizophrenia.

Large scale retrospective studies have shown an association between schizophrenia and risk of violence. Overall, this increase in risk is small and does not justify or support stigmatizing public perceptions or media depictions of people with schizophrenia. Nonetheless, in some situations, some symptoms of schizophrenia can increase the risk of violent behavior. Prediction of this behavior would allow high impact preventive interventions. However, to date the neurobiological correlates of violent behavior in schizophrenia are not well understood, precluding the development of prognostic biomarkers. We used electroencephalography to measure alpha activity and microstates from 31 patients with schizophrenia and 18 age matched controls. Participants also completed multiple assessments of current aggressive tendencies and their lifetime history of aggressive acts. We found that individual alpha peak frequency was negatively correlated with aggression scores in both patients and controls (largest Spearman's r = -0.45). Furthermore, this result could be replicated in data taken from a single frontal channel suggesting that this may be possible to obtain in routine clinical settings (largest Spearman's r = -0.40). We also found that transitions between microstates corresponding to auditory and visual networks were inversely correlated with aggression scores. Finally, we found that, within patients, aggression was correlated with the degree of randomness between microstate transitions. This suggests that aggression is related to inappropriate switching between large scale brain networks and subsequent failure to appropriately integrate complicated environmental and internal stimuli. By elucidating some of the electrophysiological correlates of aggression, these data facilitate the development of prognostic biomarkers.

"We know what we should be eating, but we don't always do that." How and why people eat the way they do: a qualitative study with rural australians.

BACKGROUND: There is evidence that most people are aware of the importance of healthy eating and have a broad understanding regarding types of food that enhance or detract from health. However, greater health literacy does not always result in healthier eating. Andreasen's Social Marketing Model and Community-Based Social Marketing both posit that, in order to change health behaviours, it is crucial to understand reasons for current behaviours and perceived barriers and benefits to improved behaviours. Limited research has been conducted, however, that explores these issues with general populations. This study aimed to help address this gap in the evidence using a qualitative methodology. METHODS: Three group discussions were conducted with a total of 23 participants: (1) young women aged 18-24 with no children; (2) women aged 35-45 with primary school aged children; and (3) men aged 35-50 living with a partner and with pre- or primary school aged children. The discussions took place in a regional centre of Victoria, Australia. Transcriptions were thematically analysed using an inductive descriptive approach and with reference to a recent integrated framework of food choice that identified five key interrelated determinants: food- internal factors; food- external factors; personal-state factors; cognitive factors; and sociocultural factors. RESULTS: We found that food choice was complex, with all five determinants evident from the discussions. However, the "Social environment" sub-category of "Food-external factors", which included family, work, and social structures, and expectations (or perceived expectations) of family members, colleagues, friends, and others, was particularly prominent. Knowledge that one should practice healthy eating, which falls under the "Cognitive factor" category, while seen as an aspiration by most participants, was often viewed as unrealistic, trumped by the need and/or desire for convenience, a combination of Food-external factor: Social environment and Personal-state factor: Psychological components. CONCLUSIONS: We found that decisions regarding what, when, and how much to eat are seen as heavily influenced by factors outside the control of the individual. It appears, therefore, that a key to improving people's eating behaviours is to make it easy to eat more healthfully, or at least not much harder than eating poorly.

Measurement of lead, mercury, and cadmium in blood donors in Canada.

BACKGROUND: Fetal and neonatal exposure to lead is associated with irreversible adverse effects on neural development. There is no reliable threshold for lead effect, so limiting exposure is recommended. A significant correlation has been reported between post-transfusion blood lead level (BLL) in infants and lead levels in transfused RBC units. We measured levels of lead, mercury, and cadmium, in Canadian donor blood to investigate if concerning levels for neonatal transfusion exist. STUDY DESIGN AND METHODS: Whole blood samples from blood donors (n = 2529) were shipped cold within 7 days of donation. All permanent blood donation clinics across Canada were sampled. Twelve of these permanent clinics and 8 mobile clinics with a greater potential for having higher lead or mercury levels were oversampled. Heavy metals were measured by inductively coupled plasma mass spectrometry. RESULTS: Of all donations, 2.2% (lead) and 0.4% (mercury) had levels higher than the recommended thresholds for safe neonatal transfusion. BLLs were higher in males but there was no significant difference in the blood mercury levels of males versus females. Cadmium levels were higher in females. There was a positive correlation between donor age and levels of heavy metals, with lead having the strongest correlation (r = 0.47, p < .0001). Three clinics in close proximity to two lead-producing mines were among the clinics with the highest BLLs. Significantly higher blood mercury levels were observed in coastal clinics. CONCLUSION: Our data on donor blood heavy metal levels supports considering blood transfusion as an exposure source to heavy metals and encourages informed selection of blood units for transfusion to vulnerable groups.

Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with Focal Segmental Glomerulosclerosis in a U.S. Real-World Database.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) leads to proteinuria and progressive decline in glomerular filtration rate which correlates with kidney failure and increased cardiovascular risk. The purpose of this study was to estimate the effects of proteinuria on kidney failure status/all-cause mortality and cardiovascular disease events/all-cause mortality, as well as the relationship between progression to kidney failure and occurrence of cardiovascular disease/mortality events among adult patients (≥18 years old) with FSGS. METHODS: This was an observational, retrospective cohort study utilizing Optum® de-identified Market Clarity Data and proprietary Natural Language Processing (NLP) data. The study period was from January 1, 2007 through March 31, 2021, with patients in the overall cohort being identified from July 1, 2007 through March 31, 2021. The index date was the first FSGS ICD-10 diagnosis code or FSGS-related NLP term within the identification period. RESULTS: Elevated proteinuria >1.5 g/g and ≥3.5 g/g increased risk for kidney failure/all-cause mortality (adjusted hazard ratio [95% CI]: 2.34 [1.99-2.74] and 2.44 [2.09-2.84], respectively) and cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 2.11 [1.38-3.22] and 2.27 [1.44-3.58], respectively). Progression to kidney failure was also associated with a higher risk of cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 3.04 [2.66-3.48]. CONCLUSIONS: A significant proportion of FSGS patients experience kidney failure and cardiovascular disease events. Elevated proteinuria and progression to kidney failure were associated with a higher risk of cardiovascular disease/all-cause mortality events, and, elevated pre-kidney failure proteinuria was associated with progression to kidney failure/all-cause mortality events. Treatments that meaningfully reduce proteinuria and slow the decline in glomerular filtration rate have the potential to reduce the risk of cardiovascular disease, kidney failure and early mortality in patients with FSGS.

Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study.

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.

Accidental paradiplomats? The curious case of Ontario school board budgets and Canadian soft power projection.

From the earliest studies of soft power in International Relations, the importance of educational exchanges has been well-established. Studies of international education in the context of Canadian soft power often draw on cases from the higher education sector. This article argues that greater attention should be paid to the K-12 level, especially as budgetary pressures in Ontario's education system are leading school boards to rapidly expand their international student recruitment efforts. Although this is not an example of intentional soft power projection, it nevertheless represents an important reminder that subnational actors may accidentally become paradiplomats whose actions have consequences on the international level. Further, this case reveals the importance of paying attention to actors typically overlooked by IR scholarship. Drawing on Joseph Nye's theory of soft power and in conversation with prior research on international education as a mechanism of soft power projection, this article traces the thread between budgetary pressures in Ontario school boards and the broader context of soft power projection.

Trends in Life Expectancy in Residential Long-Term Care by Sociodemographic Position in 1999-2018: A Multistate Life Table Study of Finnish Older Adults.

OBJECTIVES: Residential long-term care (LTC) use has declined in many countries over the past years. This study quantifies how changing rates of entry, exit, and mortality have contributed to trends in life expectancy in LTC (i.e., average time spent in LTC after age 65) across sociodemographic groups. METHODS: We analyzed population-register data of all Finns aged ≥65 during 1999-2018 (n=2,016,987) with dates of LTC and death, and sociodemographic characteristics. We estimated transition rates between home, LTC and death using Poisson generalized additive models, and calculated multistate life tables across 1999-2003, 2004-2008, 2009-2013 and 2014-2018. RESULTS: Between 1999-2003 and 2004-2008, life expectancy in LTC increased from 0.75 (95% CI 0.74-0.76) to 0.89 (0.88-0.90) years among men and from 1.61 (1.59-1.62) to 1.83 (1.81-1.85) years among women, mainly due to declining exit rates from LTC. Thereafter, life expectancy in LTC decreased, reaching 0.80 (0.79-0.81) and 1.51 (1.50-1.53) years among men and women, respectively, in 2014-2018. Especially among women and non-married men, the decline was largely due to increasing death rates in LTC. Admission rates declined throughout the study period, which offset the increase in life expectancy in LTC attributable to declining mortality in the community. Marital status differences in life expectancy in LTC narrowed over time. DISCUSSION: Recent declines in LTC use were driven by postponed LTC admission closer to death. The results suggest that across sociodemographic strata older adults enter LTC in ever worse health and spent a shorter time in care than before.

Human mitochondrial glutathione transferases: Kinetic parameters and accommodation of a mitochondria-targeting group in substrates.

Glutathione-S-transferases are key to the cellular detoxification of xenobiotics and products of oxidative damage. GSTs catalyse the reaction of glutathione (GSH) with electrophiles to form stable thioether adducts. GSTK1-1 is the main GST isoform in the mitochondrial matrix, but the GSTA1-1 and GSTA4-4 isoforms are also thought to be in the mitochondria with their distribution altering in transformed cells, thus potentially providing a cancer specific target. A mitochondria-targeted version of the GST substrate 1-chloro-2,4-dinitrobenzene (CDNB), MitoCDNB, has been used to manipulate the mitochondrial GSH pool. To finesse this approach to target particular GST isoforms in the context of cancer, here we have determined the kcat/Km for the human isoforms of GSTK1-1, GSTA1-1 and GSTA4-4 with respect to GSH and CDNB. We show how the rate of the GST-catalysed reaction between GSH and CDNB analogues can be modified by both the electron withdrawing substituents, and by the position of the mitochondria-targeting triphenylphosphonium on the chlorobenzene ring to tune the activity of mitochondria-targeted substrates. These findings can now be exploited to selectively disrupt the mitochondrial GSH pools of cancer cells expressing particular GST isoforms.

ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels.

BACKGROUND: Most organs are maintained lifelong by resident stem/progenitor cells. During development and regeneration, lineage-specific stem/progenitor cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature cells have less regenerative potential. However, it is unclear whether vascular endothelial cells (ECs) are also replenished by stem/progenitor cells with EC-repopulating potential residing in blood vessels. It has been reported recently that some EC populations possess higher clonal proliferative potential and vessel-forming capacity compared with mature ECs. Nevertheless, a marker to identify vascular clonal repopulating ECs (CRECs) in murine and human individuals is lacking, and, hence, the mechanism for the proliferative, self-renewal, and vessel-forming potential of CRECs is elusive. METHODS: We analyzed colony-forming, self-renewal, and vessel-forming potential of ABCG2 (ATP binding cassette subfamily G member 2)-expressing ECs in human umbilical vessels. To study the contribution of Abcg2-expressing ECs to vessel development and regeneration, we developed Abcg2CreErt2;ROSA TdTomato mice and performed lineage tracing during mouse development and during tissue regeneration after myocardial infarction injury. RNA sequencing and chromatin methylation chromatin immunoprecipitation followed by sequencing were conducted to study the gene regulation in Abcg2-expressing ECs. RESULTS: In human and mouse vessels, ECs with higher ABCG2 expression (ABCECs) possess higher clonal proliferative potential and in vivo vessel-forming potential compared with mature ECs. These cells could clonally contribute to vessel formation in primary and secondary recipients after transplantation. These features of ABCECs meet the criteria of CRECs. Results from lineage tracing experiments confirm that Abcg2-expressing CRECs (AbcCRECs) contribute to arteries, veins, and capillaries in cardiac tissue development and vascular tissue regeneration after myocardial infarction. Transcriptome and epigenetic analyses reveal that a gene expression signature involved in angiogenesis and vessel development is enriched in AbcCRECs. In addition, various angiogenic genes, such as Notch2 and Hey2, are bivalently modified by trimethylation at the 4th and 27th lysine residue of histone H3 (H3K4me3 and H3K27me3) in AbcCRECs. CONCLUSIONS: These results are the first to establish that a single prospective marker identifies CRECs in mice and human individuals, which holds promise to provide new cell therapies for repair of damaged vessels in patients with endothelial dysfunction.

AICAR confers prophylactic cardioprotection in doxorubicin-induced heart failure in rats.

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects, leading to heart failure (HF). Impaired mitochondrial function is thought to be key factor driving progression into HF. We have previously shown in a rat model of DOX-HF that heart failure with reduced ejection fraction correlates with mitochondrial loss and dysfunction. Adenosine monophosphate-dependent kinase (AMPK) is a cellular energy sensor, regulating mitochondrial biogenesis and energy metabolism, including fatty acid oxidation. We hypothesised that AMPK activation could restore mitochondrial function and therefore be a novel cardioprotective strategy for the prevention of DOX-HF. Consequently, we set out to assess whether 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR), an activator of AMPK, could prevent cardiac functional decline in this chronic intravenous rat model of DOX-HF. In line with our hypothesis, AICAR improved cardiac systolic function. AICAR furthermore improved cardiac mitochondrial fatty acid oxidation, independent of mitochondrial number, and in the absence of observable AMPK-activation. In addition, we found that AICAR prevented loss of myocardial mass. RNAseq analysis showed that this may be driven by normalisation of pathways associated with ribosome function and protein synthesis, which are impaired in DOX-treated rat hearts. AICAR furthermore prevented dyslipidemia and excessive body-weight loss in DOX-treated rats, which may contribute to preservation of myocardial mass. Though it is unclear whether AICAR exerted its cardioprotective effect through cardiac or extra-cardiac AMPK-activation or via an AMPK-independent effect, these results show promise for the use of AICAR as a cardioprotective agent in DOX-HF to both preserve cardiac function and mass.

A model of mitochondrial superoxide production during ischaemia-reperfusion injury for therapeutic development and mechanistic understanding.

Ischaemia-reperfusion (IR) injury is the paradoxical consequence of the rapid restoration of blood flow to an ischaemic organ. Although reperfusion is essential for tissue survival in conditions such as myocardial infarction and stroke, the excessive production of mitochondrial reactive oxygen species (ROS) upon reperfusion initiates the oxidative damage that underlies IR injury, by causing cell death and inflammation. This ROS production is caused by an accumulation of the mitochondrial metabolite succinate during ischaemia, followed by its rapid oxidation upon reperfusion by succinate dehydrogenase (SDH), driving superoxide production at complex I by reverse electron transport. Inhibitors of SDH, such as malonate, show therapeutic potential by decreasing succinate oxidation and superoxide production upon reperfusion. To better understand the mechanism of mitochondrial ROS production upon reperfusion and to assess potential therapies, we set up an in vitro model of IR injury. For this, isolated mitochondria were incubated anoxically with succinate to mimic ischaemia and then rapidly reoxygenated to replicate reperfusion, driving a burst of ROS formation. Using this system, we assess the factors that contribute to the magnitude of mitochondrial ROS production in heart, brain, and kidney mitochondria, as well as screening for inhibitors of succinate oxidation with therapeutic potential.

Inpatient Hospital Costs, Emergency Department Visits, and Readmissions for Revision Hip and Knee Arthroplasty.

BACKGROUND: Revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) tremendously burden hospital resources. This study evaluated factors influencing perioperative costs, including emergency department (ED) visits, readmissions, and total costs-of-care within 90 days following revision surgery. METHODS: A retrospective analysis of 772 revision TKAs and THAs performed on 630 subjects at a single center between January 2007 and December 2019 was conducted. Cost data were available from January 2015 to December 2019 for 277 patients. Factors examined included comorbidities, demographic information, preoperative Anesthesia Society of Anesthesiologists score, implant selection, and operative indication using mixed-effects linear regression models. RESULTS: Among 772 revisions (425 THAs and 347 TKAs), 213 patients required an ED visit, and 90 required hospital readmission within 90 days. There were 22.6% of patients who underwent a second procedure after their initial revision. Liver disease was a significant predictor of ED readmission for THA patients (multivariable odds ratio [OR]: 3.473, P = .001), while aseptic loosening, osteolysis, or instability significantly reduced the odds of readmission for TKA patients (OR: 0.368, P = .014). In terms of ED visits, liver disease increased the odds for THA patients (OR: 1.845, P = .100), and aseptic loosening, osteolysis, or instability decreased the odds for TKA patients (OR: 0.223, P < .001). Increased age was associated with increased costs in both THA and TKA patients, with significant cost factors including congestive heart failure for TKA patients (OR: $7,308.17, P = .004) and kidney disease for THA patients. Revision surgeries took longer than primary ones, with TKA averaging 3.0 hours (1.6 times longer) and THA 2.8 hours (1.5 times longer). CONCLUSIONS: Liver disease increases ED readmission risk in revision THA, while aseptic loosening, osteolysis, or instability decreases it in revision TKA. Increased age and congestive heart failure are associated with increased costs. These findings inform postoperative care and resource allocation in revision arthroplasty. LEVEL OF EVIDENCE: Economic and Decision Analysis, Level IV.

Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles.

The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse). We identify metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α is observed while downstream hypoxia responsive-genes are down-regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts show reduced succinate levels during ischemia compared to C57/BL6 mouse and negligible tissue damage following ischemia-reperfusion injury. These evolutionary traits reflect adaptation to a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span.