Marker Of Frailty Research Articles

The association between an electronic health record (EHR)–embedded frailty index and patient-reported outcomes among patients with metastatic non–small-cell lung cancer on immunotherapy.

335 Background: While frailty is a well-established predictor of overall mortality among patients with metastatic non-small cell lung cancer (mNSCLC), its association with patient-reported outcomes is not well-characterized. We assessed quality of life and symptom burden by frailty status among mNSCLC patients receiving immunotherapy. We used an electronic health record (EHR) frailty index (eFI) as a marker of frailty. In addition, we assessed self-perceived goals of treatment by frailty status. Methods: In a cross-sectional study, patients from a single academic medical center with mNSCLC who were on first or second-line immunotherapy or chemoimmunotherapy completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) and the National Cancer Institute Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). In addition completed the Prognosis Treatment and Perceptions Questionnaire. We computed means of EORTC-QLQ-C30 subscales and proportions reporting at least moderate PRO-CTCAE symptoms, and compared results across three levels of frailty status using the eFI (which uses 54 variables from the EHR to calculate a score from 0-1), which categorizes frailty status as either fit (eFI ≤0.10), pre-frail (0.10 < eFI≤0.21), or frail (eFI > 0.21). P-values for comparisons of continuous variables were derived from F-tests from ANOVA models, while those for comparisons of categorical variables were derived from chi-square or Fisher’s exact tests. Results: Sixty patients (mean age 62.5 years, 75% Caucasian, 60% women, 57% receiving single-agent immunotherapy) participated. Most patients were pre-frail (68%), with few categorized as fit (18%) or frail (n=15%). The EORTC-QLQ-C30 global health score was similar among frailty categories (mean 62.6). Among EORTC functional subscales, only physical function differed by frailty status (mean 83.9 fit vs 74.8 pre-frail vs 60.0 frail, p-value 0.04). We found no differences in any of the EORTC-QLQ-C30 symptom subscales across frailty categories. On the PRO-CTCAE measures, only self-reported pain differed among the three groups, with pain being higher among frail patients (75% of frail reporting at least moderate pain, vs 51.5% of pre-frail and 18.2% of fit; p=0.046). No differences in self-perceived goals of treatment or likelihood of cure emerged by frailty status. Conclusions: Frail patients identified by the eFI with mNSCLC have higher rates of pain and physical functional impairments but similar perspectives on likelihood of cure as those without frailty. This highlights the importance of symptom monitoring and frailty screening along with prognostic discussions in those with mNSCLC. Clinical trial information: NCT03741868 .

Adjusting expected deaths for mortality displacement during the COVID-19 pandemic: a model based counterfactual approach at the level of individuals

BackgroundNear-real time surveillance of excess mortality has been an essential tool during the COVID-19 pandemic. It remains critical for monitoring mortality as the pandemic wanes, to detect fluctuations in the death rate associated both with the longer-term impact of the pandemic (e.g. infection, containment measures and reduced service provision by the health and other systems) and the responses that followed (e.g. curtailment of containment measures, vaccination and the response of health and other systems to backlogs). Following the relaxing of social distancing regimes and reduction in the availability of testing, across many countries, it becomes critical to measure the impact of COVID-19 infection. However, prolonged periods of mortality in excess of the expected across entire populations has raised doubts over the validity of using unadjusted historic estimates of mortality to calculate the expected numbers of deaths that form the baseline for computing numbers of excess deaths because many individuals died earlier than they would otherwise have done: i.e. their mortality was displaced earlier in time to occur during the pandemic rather than when historic rates predicted. This is also often termed “harvesting” in the literature.MethodsWe present a novel Cox-regression-based methodology using time-dependent covariates to estimate the profile of the increased risk of death across time in individuals who contracted COVID-19 among a population of hip fracture patients in England (N = 98,365). We use these hazards to simulate a distribution of survival times, in the presence of a COVID-19 positive test, and then calculate survival times based on hazard rates without a positive test and use the difference between the medians of these distributions to estimate the number of days a death has been displaced. This methodology is applied at the individual level, rather than the population level to provide a better understanding of the impact of a positive COVID-19 test on the mortality of groups with different vulnerabilities conferred by sociodemographic and health characteristics. Finally, we apply the mortality displacement estimates to adjust estimates of excess mortality using a “ball and urn” model.ResultsAmong the exemplar population we present an end-to-end application of our methodology to estimate the extent of mortality displacement. A greater proportion of older, male and frailer individuals were subject to significant displacement while the magnitude of displacement was higher in younger females and in individuals with lower frailty: groups who, in the absence of COVID-19, should have had a substantial life expectancy.ConclusionOur results indicate that calculating the expected number of deaths following the first wave of the pandemic in England based solely on historical trends results in an overestimate, and excess mortality will therefore be underestimated. Our findings, using this exemplar dataset are conditional on having experienced a hip fracture, which is not generalisable to the general population. Fractures that impede mobility in the weeks that follow the accident/surgery considerably shorten life expectancy and are in themselves markers of significant frailty. It is therefore important to apply these novel methods to the general population, among whom we anticipate strong patterns in mortality displacement – both in its length and prevalence – by age, sex, frailty and types of comorbidities. This counterfactual method may also be used to investigate a wider range of disruptive population health events. This has important implications for public health monitoring and the interpretation of public health data in England and globally.

Back Extensor Strength as a Potential Marker of Frailty Using Propensity Score Matching and Machine Learning.

This study assessed the potential of back extensor strength as an alternative marker of frailty. A total of 560 farmers were included. Computed tomography scans measured fat and muscle mass volumes at the mid-L4 vertebral level. Back extensor strength was measured in a seated posture. Multivariate linear regression was used to analyze the associations between back extensor strength and trunk muscle/fat compositions. The participants were divided into two groups based on back extensor strength. Propensity score matching, multivariate logistic regression, and Extreme Gradient Boosting (XGBoost) were employed to evaluate the relationship between Fried's frailty criteria and back extensor strength. Back extensor strength exhibited positive associations with abdominal muscle volume (r = 1.12) as well as back muscle volume (r = 0.89) (p < 0.05). Back extensor strength was linked to more frail status, such as reduced grip strength, walking speed, and frequent self-reported exhaustion. Multivariate logistic regression indicated that back extensor strength was associated with higher frail status (OR = 0.990), and XGBoost analysis identified back extensor strength as the most important predictor (gain = 0.502) for frailty. The prediction models using grip strength produced similar results (OR = 0.869, gain = 0.482). These findings suggested the potential of back extensor strength as an alternative frailty marker.

Low Alanine-Aminotransferase Blood Activity Is Associated with Increased Mortality in Chronic Lymphocytic Leukemia Patients: A Retrospective Cohort Study of 716 Patients.

Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies, especially among elderlies. Several prognostic scores are available that utilize the characteristics of patients' blood counts and cytogenetic anomalies-all are features of the disease rather than of the patient. Addressing the route of personalized rather than precise medicine, we refer to the assessment of patients' status of sarcopenia and frailty. Low alanine aminotransferase (ALT) was already shown to function as a surrogate marker for sarcopenia and frailty. We decided to find a possible correlation between low ALT values and poor prognosis of CLL patients. This is a retrospective cohort study of CLL patients treated in a large, tertiary medical center, as outpatients or inpatients. Their frailty status was evaluated in a retrospective manner. We defined patients with ALT below 12 IU/L as frail and divided our cohort into two groups including a low ALT level group (ALT < 12) and a normal ALT level group (ALT ≥ 12). Overall, our final analysis included 716 CLL patients, of which 161 (22.5%) had ALT levels lower than 12 IU/L. There was no significant difference in patients' age between the two groups. Patients with the low ALT had a lower hemoglobin concentration (median 10.8 g/dL [IQR = 2.7] vs. 12.2 [IQR = 3.1]; p < 0.001) and a higher proportion of patients were classified as Binet C score [48.4% vs. 31.1%]; p < 0.001). Frail CLL patients' survival was significantly shorter when compared to non-frail patients, in both the univariate [HR = 1.6 [95% confidence interval, CI 1.23, 2.0]; p < 0.01] and multivariate analyses [HR = 1.3 [95% CI 1.0, 1.7]; p = 0.03]. Sarcopenia and frailty assessment, based on blood ALT measurements, could potentially point out differences in CLL patients' prognoses. Such assessment could serve the purpose of treatment personalization of CLL patients.

The effect of frailty and age on outcomes in elective paraesophageal hernia repair.

Paraesophageal hernia repair (PEHR) is a safe and effective operation. Previous studies have described risk factors for poor peri-operative outcomes such as emergent operations or advanced patient age, and pre-operative frailty is a known risk factor in other major surgery. The goal of this retrospective cohort study was to determine if markers of frailty were predictive of poor peri-operative outcomes in elective paraesophageal hernia repair. Patients who underwent elective PEHR between 1/2011 and 6/2022 at a single university-based institution were identified. Patient demographics, modified frailty index (mFI), and post-operative outcomes were recorded. A composite peri-operative morbidity outcome indicating the incidence of any of the following: prolonged length of stay (≥ 3days), increased discharge level of care, and 30-day complications or readmissions was utilized for statistical analysis. Descriptive statistics and logistic regression were used to analyze the data. Of 547 patients who underwent elective PEHR, the mean age was 66.0 ± 12.3, and 77.1% (n = 422) were female. Median length of stay was 1 [IQR 1, 2]. ASA was 3-4 in 65.8% (n = 360) of patients. The composite outcome occurred in 32.4% (n = 177) of patients. On multivariate analysis, increasing age (OR 1.021, p = 0.02), high frailty (OR 2.02, p < 0.01), ASA 3-4 (OR 1.544, p = 0.05), and redo-PEHR (OR 1.72, p = 0.02) were each independently associated with the incidence of the composite outcome. On a regression of age for the composite outcome, a cutoff point of increased risk is identified at age 72years old (OR 2.25, p < 0.01). High frailty and age over 72years old each independently confer double the odds of a composite morbidity outcome that includes prolonged post-operative stay, peri-operative complications, the need for a higher level of care after elective paraesophageal hernia repair, and 30-day readmission. This provides additional information to counsel patients pre-operatively, as well as a potential opportunity for targeted pre-habilitation.

Do low levels of alanine aminotransferase, a baseline marker of sarcopenia and frailty, associate with worse clinical outcomes among hospitalized COVID-19 patients? A Retrospective Cohort Study.

COVID-19 geoperdize lives. Not all the risk factors for negative outcomes are known. Sarcopenia and frailty are common, negatively affecting clinical outcomes. Studies have shown that sarcopenia and frailty are associated with worse outcomes. Our objective was to examine whether low ALT (Alanine-aminotranferase), a surrogate marker for sarcopenia, is associated with worse clinical outcomes among hospitalized COVID-19 patients. We reviewed cases of COVID-19 in a tertiary hospital, during three COVID-19 waves and examined correlations between ALT and mortality using crude, univariate and multivariate analysis for age, gender, hypertension, Chronic obstructive pulmonary disease and Congestive heart failure. 357 patients were included in this analysis. Median age was 69, 54% were males. Median ALT was 19 IU/L. During follow-up, 73 (20%) died. Patients with low ALT were more likely to die (HR 1.82, 95% CI 1.06-3.09, P=0.028). Other predictors for mortality were low albumin, background COPD, dyslipidemia, dementia, and malignancy. The multivariate analysis showed that low ALT was still an independent predictor of poor prognosis (HR 1.7, 95% CI 1.0-2.9, P=0.049). In our analysis of COVID-19 patients, low ALT levels were independently associated with increased risk of mortality, both as standalone and when incorporated into a multivariate analysis.

The relationship and predictive value of dementia and frailty for mortality in patients with surgically managed hip fractures

BackgroundBoth dementia and frailty have been associated with worse outcomes in patients with hip fractures. However, the interrelation and predictive value of these two entities has yet to be clarified. The current study aimed to investigate the predictive relationship between dementia, frailty, and in-hospital mortality after hip fracture surgery.MethodsAll patients registered in the 2019 National Inpatient Sample Database who were 50 years or older and underwent emergency hip fracture surgery following a traumatic fall were eligible for inclusion. Logistic regression (LR) models were constructed with in-hospital mortality as the response variables. One model was constructed including markers of frailty and one model was constructed excluding markers of frailty [Orthopedic Frailty Score (OFS) and weight loss]. The feature importance of all variables was determined using the permutation importance method. New LR models were then fitted using the top ten most important variables. The area under the receiver-operating characteristic curve (AUC) was used to compare the predictive ability of these models.ResultsAn estimated total of 216,395 patients were included. Dementia was the 7th most important variable for predicting in-hospital mortality. When the OFS and weight loss were included, they replaced dementia in importance. There was no significant difference in the predictive ability of the models when comparing the model that included markers of frailty [AUC for in-hospital mortality (95% CI) 0.79 (0.77–0.81)] with the model that excluded markers of frailty [AUC for in-hospital mortality (95% CI) 0.79 (0.77–0.80)].ConclusionDementia functions as a surrogate for frailty when predicting in-hospital mortality in hip fracture patients. This finding highlights the importance of early frailty screening for improvement of care pathways and discussions with patients and their families in regard to expected outcomes.

Clinical spectrum and prognostic impact of cancer in critically ill patients with HIV: a multicentre cohort study

BackgroundBoth AIDS-defining and non-AIDS-defining cancers (ADC/NADC) predispose people living with HIV (PLHIV) to critical illnesses. The objective of this multicentre study was to investigate the prognostic impact of ADC and NADC in PLHIV admitted to the intensive care unit (ICU).MethodsAll PLHIV admitted over the 2015–2020 period in 12 university-affiliated ICUs in France were included in the study cohort. The effect of ADC and NADC on in-hospital mortality (primary study endpoint) was measured through logistic regression with augmented backward elimination of potential independent variables. The association between ADC/NADC and treatment limitation decision (TLD) during the ICU stay (secondary study endpoint) was analysed. One-year mortality in patients discharged alive from the index hospital admission (exploratory study endpoint) was compared between those with ADC, NADC or no cancer.ResultsAmongst the 939 included PLHIV (median age, 52 [43–59] years; combination antiretroviral therapy, 74.4%), 97 (10.3%) and 106 (11.3%) presented with an active NADC (mostly lung and intestinal neoplasms) and an active ADC (predominantly AIDS-defining non-Hodgkin lymphoma), respectively. Inaugural admissions were common. Bacterial sepsis and non-infectious neoplasm-related complications accounted for most of admissions in these subgroups. Hospital mortality was 12.4% in patients without cancer, 30.2% in ADC patients and 45.4% in NADC patients (P < 0.0001). NADC (adjusted odds ratio [aOR], 7.00; 95% confidence interval [CI], 4.07–12.05) and ADC (aOR, 3.11; 95% CI 1.76–5.51) were independently associated with in-hospital death after adjustment on severity and frailty markers. The prevalence of TLD was 8.0% in patients without cancer, 17.9% in ADC patients and 33.0% in NADC patients (P < 0.0001)—organ failures and non-neoplastic comorbidities were less often considered in patients with cancer. One-year mortality in survivors of the index hospital admission was 7.8% in patients without cancer, 17.0% in ADC patients and 33.3% in NADC patients (P < 0.0001).ConclusionsNADC and ADC are equally prevalent, stand as a leading argument for TLD, and strongly predict in-hospital death in the current population of PLHIV requiring ICU admission.

Depression and Malnutrition for Prediction of Mortality after Transcatheter Aortic Valve Replacement: A Registry Study of a Tertiary Referral Hospital.

Moderate to severe frailty is a predictor of a poor outcome after transcatheter aortic valve replacement (TAVR), but little is known about the prognostic importance of different geriatric frailty markers in an overall fit or pre-frail geriatric population undergoing TAVR. This retrospective study aimed to examine the incremental value of adding patient frailty markers to conventional surgical risk score to predict all-cause mortality in relatively fit elderly patients undergoing TAVR. Overall patient frailty was assessed using the comprehensive geriatric assessment frailty index (CGA-FI). Multivariable Cox regression models were used to evaluate relationships of different geriatric frailty markers with all-cause mortality and single and combined frailty models were compared to a baseline model that included EuroSCORE II factors. One hundred relatively fit geriatric patients (84 ± 4 years old, mean CGA-FI 0.14 ± 0.05) were included, and 28% died during a median follow-up of 24 months. After adjustment, risk of depression (geriatric depression scale 15 (GDS-15)) and malnutrition remained significantly associated with all-cause mortality (HR 4.381, 95% CI 1.787-10.743; p = 0.001 and HR 3.076, 95% CI 1.151-8.217; p = 0.025, respectively). A combined frailty marker model including both GDS-15 and malnutrition on top of EuroSCORE II improved the discriminative ability to predict all-cause mortality (change in c-index: + 0.044). Screening for those frailty markers on top of the traditionally used EuroSCORE II may improve risk stratification and prognosis in relatively fit geriatric patients undergoing TAVR.

Psoas muscle analysis as a surrogate marker of sarcopenia and frailty: A multicenter analysis of predictive capacities over short- and long-term outcomes after abdominal aortic aneurysm repair.

Several predictive models exist for estimating the postoperative risks of abdominal aortic aneurysm (AAA) repair, although no particular tool has seen widespread use. We present the results of a multicenter, historic cohort study comparing the predictive capacity of the psoas muscle area (PMA), radiodensity (PMD), and lean muscle area (LMA) as surrogate markers of sarcopenia, over short- and long-term outcomes after AAA repair, compared to the mFI-5 and American Society of Anesthesiologists (ASA) scales. Retrospective review was conducted of all consecutive AAA elective repair cases (open or endovascular) in three tertiary-care centers from 2014 to 2019. Cross-sectional PMA, PMD, and LMA at the mid-body of the L3 vertebra were measured by two independent operators in the preoperative computed tomography. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff values. Bivariate analysis, logistic regression, and Cox's proportional hazards models were built to examine the relationship between baseline variables and postoperative mortality, long-term mortality, and complications. 596 patients were included (mean age 72.7 ± 8years, 95.1% male, 66.9% EVAR). Perioperative mortality was 2.3% (EVAR 1.2% vs open repair 4.6%, p = .015), and no independent predictors could be identified in the multivariate analysis. Conversely, an age over 74years old (OR 1.84 95%CI 1.25-2.70), previous heart diseases (OR 1.62 95%CI 1.13-2.32), diabetes mellitus (OR 1.61 95%CI 1.13-2.32), and a PMD value over 66 HU (OR 0.58 95%CI 0.39-0.84) acted as independent predictors of long-term mortality in the Cox's proportional hazards model. Heart diseases (congestive heart failure or coronary artery disease), serum creatinine levels over 1.05mg/dL, and an aneurysm diameter over 60mm were independent predictors of major complications. Surrogate markers of sarcopenia had a poor predictive profile for postoperative mortality after AAA repair in our sample. However, PMD stood out as an independent predictor of long-term mortality. This finding can guide future research and should be confirmed in larger datasets.

Cholesterol alone or in combination is associated with frailty among community-dwelling older adults: A cross-sectional study

BackgroundBiological markers contribute to the precise intervention across the continuum of frailty severity. Few studies have explored the advantages of biological markers collected as part of primary care data among community-dwelling older adult population and controversy remains regarding the classic biological markers for frailty. MethodsWe recruited a total of 8791 adults with a mean age of 71.95 years who met the inclusion and exclusion criteria in Guancheng District and Dalang Town, Dongguan, China. Frailty was assessed by a Chinese frailty evaluation scale. Frailty status was classified with 33-item modified frailty index and latent class analysis was applied to explore the latent classes (subtypes) of frailty. We measured biological markers on blood samples collected. We identify association between specific biological markers or patterns and frailty by logistic regression and association rule mining (ARM) based on the Apriori algorithm. ResultsMultivariable analysis of our data showed that an elevated white blood cell (WBC) count and high cholesterol (CHOL) level were associated with pre-frailty (adjusted odds ratio [aOR] = 1.231, 95 % confidence interval [CI] = 1.009–1.501; aOR = 0.703, 95 % CI = 0.623–0.793) and frailty (aOR = 1.500, 95 % CI = 1.130–1.993; aOR = 0.561, 95 % CI = 0.461–0.684) compared with the normal groups. Importantly, significantly high level of CHOL was associated with a lower risk of four frailty subtypes compared with relatively healthy participants with the most power of association in the multi-frail group (aOR = 0.182, 95 % CI = 0.086–0.386). Based on ARM technique to develop correlation analysis to identify important high-risk clusters among older adult transitions from non-frail to frailty, patterns for normal level of CHOL co-occurred with an elevated creatinine (CREA) level have a significant association with the risk of frailty (aOR = 7.787, 95 % CI = 1.978–30.648) after adjusting for targeted confounders. ConclusionsOur study highlights the correlation between classic biological markers, especially CHOL and frailty status and subtypes among community-dwelling older adult, in the primary care setting. Further large-scale prospective studies are still needed to confirm the role of classic biological markers in frailty.

Exploring Olfactory Dysfunction as a Marker of Frailty and Postoperative Outcomes in Head and Neck Cancer

Olfactory dysfunction (OD) is increasingly recognized as a robust marker of frailty and mortality. Despite broad recognition of frailty as a critical component of head and neck cancer (HNC) care, there is no standardized frailty assessment. To assess the prevalence of OD and its association with frailty and postoperative outcomes in HNC. In this prospective cohort study with enrollment between February 17, 2021, to September 29, 2021, at a tertiary academic medical center, 85 eligible adult patients with primary, treatment-naive HNC of mucosal or cutaneous origin were included. Patients with a history of COVID-19, neurocognitive, or primary smell/taste disorders were excluded. Prospective olfactory assessments (self-reported, visual analog scale [VAS] and psychophysical, University of Pennsylvania Smell Identification Test [UPSIT]) with concurrent frailty assessment (Risk Analysis Index [RAI]) were used. Olfactory-specific quality of life (QOL) was examined with brief Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). The primary outcome was the prevalence of OD as assessed by VAS (0-10, no to normal smell) and UPSIT (0-40, higher scores reflect better olfaction) and its association with frailty (RAI, 0-81, higher scores indicate greater frailty). For surgical patients, secondary outcomes were associations between OD and postoperative length of stay (LOS), 30-day postoperative outcomes, and QOD-NS (0-21, higher scores indicate worse QOL). Among 51 patients with HNC (mean [SD] age, 63 [10] years; 39 [77%] male participants; 41 [80%] White participants), 24 (47%) were frail, and 4 (8%) were very frail. Despite median (IQR) self-reported olfaction by VAS of 9 (8-10), 30 (59%) patients demonstrated measured OD with psychophysical testing. No meaningful association was found between self-reported and psychophysical testing (Hodges-Lehmann, <0.001; 95% CI, -2 to 1); a total of 46 (90%) patients did not report decreased olfaction-specific QOL. Median UPSIT scores were lower in frail patients (Hodges-Lehmann, 6; 95% CI, 2-12). Multivariate modeling demonstrated severe microsmia/anosmia was associated with 1.75 (95% CI, 1.09-2.80) times odds of being frail/very frail and approximately 3 days increased LOS (β, 2.96; 95% CI, 0.29-5.62). Although patients with HNC are unaware of olfactory changes, OD is common and may serve as a bellwether of frailty. In this prospective cohort study, a dose-dependent association was demonstrated between increasing degrees of OD and frailty, and the potential utility of olfaction was highlighted as a touchstone in the assessment of HNC frailty.

Investigation of frailty markers including a novel biomarker panel in emergency laparotomy: protocol of a prospective cohort study

BackgroundEmergency laparotomy (EmLAP) is one of the commonest emergency operations performed in the United Kingdom (approximately 30, 000 laparotomies annually). These potentially high-risk procedures can be life changing with frail patients and/ or older adults (≥ 65 years) having the poorest outcomes, including mortality. There is no gold standard of frailty assessment and no clinical chemical biomarkers existing in practice. Early detection of subclinical changes or deficits at the molecular level are essential in improving our understanding of the biology of frailty and ultimately improving patient outcomes. This study aims primarily to compare preoperative frailty markers, including a blood-based biomarker panel, in their ability to predict 30 and 90-day mortality post-EmLAP. The secondary aim is to analyse the influence of perioperative frailty on morbidity and quality of life post-EmLAP.MethodsA prospective single centred observational study will be conducted on 150 patients ≥ 40 years of age that undergo EmLAP. Patients will be included according to the established NELA (National Emergency Laparotomy Audit) criteria. The variables collected include demographics, co-morbidities, polypharmacy, place of residence, indication and type of surgery (as per NELA criteria) and prognostic NELA score. Frailty will be assessed using: a blood sample for ultra-high performance liquid chromatography mass spectrometry analysis; preoperative CT abdomen pelvis (sarcopenia) and Rockwood Clinical Frailty Scale (CFS). Patients will be followed up for 90 days. Variables collected include blood samples (at post operative day 1, 7, 30 and 90), place of residence on discharge, morbidity, mortality and quality of life (EQ-5D-5 L). The frailty markers will be compared between groups of frail (CFS ≥ 4) and non-frail using statistical methods such as regression model and adjusted for appropriate confounding factors.DiscussionThis study hypothesises that frailty level changes following EmLAP in frail and non- frail patients, irrespective of age. We propose that non- frail patients will have better survival rates and report better quality of life compared to the frail. By studying the changes in metabolites/ biomarkers in these patients and correlate them to frailty status pre-surgery, this highly novel approach will develop new knowledge of frailty and define a new area of clinical biomolecular research.Trial registrationClinicalTrials.gov: NCT05416047. Registered on 13/06/2022 (retrospectively registered).

Frailty and Clinical Outcomes in Patients Treated With Hemodialysis: A Prospective Cohort Study

Frailty is common among people with kidney failure treated with hemodialysis (HD). The objective was to describe how frailty evolves over time in people treated by HD, how improvements in frailty and frailty markers are associate with clinical outcomes, and the characteristics that are associated with improvement in frailty. Prospective cohort study. Adults initiating thrice weekly in-center HD in Canada. We classified frailty using a 5-point score (3 or more indicates frailty) based on physical inactivity, slowness or weakness, poor endurance or exhaustion, and malnutrition. We categorized the frailty trajectory as never present, improving, deteriorating, and always present. All-cause death, hospitalizations, and placement into long-term care. We examined the association between time-varying frailty measures and these outcomes using Cox and negative binomial models, after adjustment for potential confounders. 985 participants were included and followed up for a median of 33 months; 507 (51%) died, 761 (77%) experienced≥1 hospitalization and 115 (12%) entered long-term care. Overall, 760 (77%) reported frailty during follow-up. Three-quarters (78%) of those with frailty at baseline remained frail throughout the follow-up, 46% without baseline frailty became frail, and 23% with baseline frailty became nonfrail. Higher frailty scores were associated with an increased risk of mortality (fully adjusted HR, 1.58 per unit; 95% CI, 1.39-1.80) and an increased rate of hospitalization (RR, 1.16 per unit; 95% CI, 1.09-1.23). Compared with those who were frail throughout the follow-up, participants with frailty at baseline but improving during follow-up showed a lower mortality (HR, 0.59; 95% CI, 0.42-0.81), and a lower rate of hospitalization (RR, 0.70; 95% CI, 0.56-0.87). There was missing data on frailty at baseline and during follow-up. Frailty was associated with a higher risk of poor outcomes compared with those without frailty, and participants whose status improved from frail to nonfrail showed better clinical outcomes than those who remained frail. These findings emphasize the importance of identifying and implementing effective treatments for frailty in patients receiving maintenance HD.

Identifying Frailty in Older Adults in Rural Victoria, Australia: A Secondary Analysis of Population Health Data.

Objectives: To determine the prevalence of frailty among community-dwelling older adults in regional Victoria, Australia. Methods: Frailty status of 376 participants from the Crossroads II cross-sectional study was assessed by selected markers of frailty. The selected variables were psychometrically tested. Associations between frailty and socio-demographic, environmental and health factors were analysed using chi-square, ANOVA and binary logistic regression (BLR). Results: Estimated prevalence of frailty was 39.4%. BLR indicated that frailty decreased with higher educational attainment, (OR = .23; 95% CI: .10-.51) increased for divorced/separated participants (OR = 2.68; 95% CI: 1.29-5.56) and when having three (OR = 3.27; 95% CI: 1.07-9.98), four (OR = 7.20; 95% CI: 2.22-23.31) or five or more chronic conditions (OR = 9.18; 95% CI: 2.83-29.72). Discussion: Frailty in this Australian regional community-dwelling sample was higher than other studies conducted in urban areas of Australia. Present results highlight the importance of exploring the multidimensionality of the frailty construct to have a better understanding which factors are associated with the development of this syndrome.

P.148 Perceptions of frailty in spinal metastatic disease: international survey of the AO spine community

Background: Frailty is increasingly recognized for an association with adverse events, mortality, and hospital discharge disposition among surgical patients. The purpose of this study was to describe how spinal surgeons conceptualize, define, and assess frailty in the context of spinal metastatic disease (SMD). Methods: We conducted an international, cross-sectional, 33-question survey of the AO Spine community. The survey was developed using a modified Delphi technique and was designed to elucidate preoperative surrogate markers of frailty in the context of SMD. Responses were ranked using weighted averages. Consensus was defined as ≥ 70% agreement among respondents. Results: Results were analyzed for 312 respondents (86% completion rate). Study participants represented 71 countries. Most respondents informally assess frailty in patients with SMD by forming a general perception based on clinical condition and patient history. Consensus was attained regarding the association between 14 clinical variables and frailty. Severe comorbidities, systemic disease burden, and poor performance status were most associated with frailty; severe comorbidities included high-risk cardio-pulmonary disease, renal failure, liver failure, and malnutrition. Conclusions: Surgeons recognized frailty is important but commonly evaluate it based on general clinical impression rather than using existing frailty tools. We identified preoperative surrogate markers of frailty perceived as most relevant in this population.

Critically ill patients with acute kidney injury: clinical determinants and post-mortem histology.

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) in the intensive care unit (ICU) portends a poor prognosis. We aimed to better characterize predictors of survival and the mechanism of kidney failure in these patients. This was a retrospective observational study using clinical and radiological electronic health records, analysed by univariable and multivariable binary logistic regression. Histopathological examination of post-mortem renal tissue was performed. Among 157 patients with AKI requiring RRT, higher serum creatinine at RRT initiation associated with increased ICU survival [odds ratio (OR) 0.33, 95% confidence interval (CI) 0.17-0.62, P=.001]; however, muscle mass (a marker of frailty) interacted with creatinine (P=.02) and superseded creatinine as a predictor of survival (OR 0.26, 95% CI 0.08-0.82; P=.02). Achieving lower cumulative fluid balance (mL/kg) predicted ICU survival (OR 1.01, 95% CI 1.00-1.01, P<.001), as supported by sensitivity analyses showing improved ICU survival with the use of furosemide (OR 0.40, 95% CI 0.18-0.87, P=.02) and increasing net ultrafiltration (OR 0.97, 95% CI 0.95-0.99, P=.02). A urine output of >500 mL/24 h strongly predicted successful liberation from RRT (OR 0.125, 95% CI 0.05-0.35, P<.001). Post-mortem reports were available for 32 patients; clinically unrecognized renal findings were described in 6 patients, 1 of whom had interstitial nephritis. Experimental staining of renal tissue from patients with sepsis-associated AKI (S-AKI) showed glomerular loss of synaptopodin (P=.02). Confounding of creatinine by muscle mass undermines its use as a marker of AKI severity in clinical studies. Volume management and urine output are key determinants of outcome. Loss of synaptopodin implicates glomerular injury in the pathogenesis of S-AKI.

MRI Assessment of Brain Frailty and Clinical Outcome in Patients With Acute Posterior Perforating Artery Infarction.

Global brain health has gained increasing attention recently. Imaging markers of brain frailty have been related to functional outcomes in previous studies on anterior circulation; however, little data are available on imaging markers and posterior circulation. To investigate the impact of brain frailty on functional outcomes in patients with acute perforating artery infarction (PAI) of the posterior circulation. Prospective. One hundred patients (60.78 ± 9.51 years, 72% men) with acute posterior circulation PAI (determined by diffusion-weighted magnetic resonance imaging (MRI)/time-of-flight MR angiography). T1- and T2-weighted fast spin echo, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted echo planar, gradient echo (susceptibility-weight imaging), and 3D time-of-flight MR angiography sequences at 3.0 T. Periventricular and deep white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS) in the basal ganglia and centrum semiovale area, lacunes, cerebral microbleeds (CMB), and total brain frailty score by calculating the above imaging characters were rated visually by three radiologists with 9, 10, and 11 years of experience and one neuroradiologist with 12. Infarction volume was assessed using baseline diffusion-weighted imaging (DWI) data obtained within 24 hours of symptom onset. A modified Rankin Scale (mRS) score >1 on day 90 defined an adverse functional outcome. Associations between the imaging markers of brain frailty and functional outcomes were assessed. Fisher's exact test, Mann-Whitney U test, and multivariable binary logistic regression. A P value <0.05 was considered statistically significant. Adverse prognoses (mRS > 1) were observed in 34 (34%) patients. Infarction volume, periventricular WMH, deep WMH, basal ganglia EPVS, CMB, and the brain frailty score were significantly associated with adverse functional outcomes. An increased brain frailty score was significantly associated with unfavorable mRS score on day 90 (odds ratio 1.773, 95% confidence interval 1.237-2.541). Advanced MRI imaging markers of brain frailty, individually or combined as a total brain frailty score, were associated with worse functional outcomes after acute posterior circulation PAI. 3 TECHNICAL EFFICACY: Stage 3.

Effects of COVID-19 Lockdown on Nutritional, Functional and Frailty Biomarkers of People Living in Nursing Homes. A Prospective Study.

Nursing home residences suffered a lockdown from the beginning of the COVID-19 pandemic. The present study prospectively evaluates the frailty, functional, and nutritional statuses of nursing home residents. Three hundred and one residents from three nursing homes took part in the study. Frailty status was measured using the FRAIL scale. Functional status was evaluated using the Barthel Index. Additionally, Short Physical Performance Batter (SPPB), SARC-F, hand-grip strength, and gait speed were also evaluated. Nutritional status was determined using the mini nutritional assessment test (MNA) and several anthropometrical and biochemical markers. Mini Nutritional Assessment test scores decreased in 20% throughout the confinement (p < .001). Barthel index, SPPB and SARC-F scores also decreased, although to a lesser extent, reflecting a decrease in functional capacity. However, both anthropometric parameters, hand grip strength and gait speed, remained stable throughout confinement (p > .050 in all cases). Morning cortisol secretion significantly decreased by 40% from baseline to post-confinement. A significant reduction in daily cortisol variability was observed, which may suggest increased distress. Fifty-six residents died during the period of confinement (81.4% survival rate). Sex, FRAIL and Barthel Index scores were significant predictors of resident survival. After the first COVID-19 blockade, several alterations in residents' frailty markers were observed, which were small and potentially reversible. However, many of the residents were pre-frail after the lockdown. This fact highlights the need for preventive strategies to reduce the impact of future social and physical stressors on these vulnerable individuals.

Low ALT, a marker of sarcopenia and frailty, is associated with shortened survival amongst myelodysplastic syndrome patients: A retrospective study.

Myelodysplastic Syndrome (MDS) is a common blood dyscrasia that mainly affects the elderly population. Several prognostic scores are available utilizing blood count variables and cytogenetic abnormalities, targeting the disease rather than the patient. Sarcopenia and frailty are associated with shortened survival rates in various disease states. Low Alanine Aminotransferase (ALT) levels are a marker of lowered muscle mass and frailty status. This study aimed to examine the correlation between low ALT levels and prognosis in MDS patients. This is a retrospective cohort study. We obtained the demographic, clinical, and laboratory data of patients in a tertiary hospital. Univariate and multivariate models were used to investigate the potential relationship between low ALT level and survival. The final study included 831 patients (median age 74.3 years, Interquartile range 65.6-81.8), and 62% were males. The median ALT level was 15 international units (IU)/L and 233 patients (28%) had low ALT levels (<12 IU/L). Univariate analysis showed that low ALT levels were associated with a 25% increase in mortality (95% confidence interval [CI]: 1.05-1.50, P = .014). A multivariate model controlling for age, sex, body mass index, hemoglobin and albumin concentrations, and low ALT levels was still significantly associated with increased mortality (hazard ratio [HR] = 1.25, 95% CI: 1.01-1.56, P = .041). Low ALT levels were associated with increased mortality among patients with MDS. Impact: Using ALT as a frailty metric may allow patient-centered, personalized care in this patient population. A low ALT level reflects the pre-morbid robustness of patients and is not intended to replace disease-centered characteristics.