Frailty Scale for Outcome Predictions in Hematopoietic Cell Transplanted Adults

INTRODUCTION Frailty in patients undergoing hematopoietic cell transplantation (HCT) has a negative impact on survival. The inclusion of frailty evaluations before HCT is highly recommended; however, there is no consensus about the best methodology to evaluate this syndrome. In 2018 our center started a Frailty and Functionality program that involves regularly collecting information on the following eight indices in patients referred for allogeneic HCT (Salas et al., 2021): Clinical Frailty Scale (CFS), Instrumental Activities of Daily Living (IADL) test, Timed up and Go Test (TUGT), Grip Strength (GS), Self-Health Rated questionnaire (SHR-Q), Fall test, albumin (Alb), and C - reactive protein (CRP). With the recorded measurements of the eight indices and the corresponding validating process, we propose a HCT Frailty Scale. This scale is specifically designed to identify fit, pre-frail, and frail candidates for alloHCT, from better to worst probability of post-transplant survival. METHODS Between June 2018 and December 2020, 338 adults underwent alloHCT at our Institution. Frailty syndrome was evaluated prospectively in all patients at first consultation, using existing resources, after informed consent. It included measurement of the eight indices. The median time to evaluate was 5-6 minutes. Each index was given a value of 0 if normal or 1 (abnormal). Complete data were available for 298 patients that were finally included in the analysis. With this data the HCT Frailty Scale was elaborated as follows. The study cohort was split in two groups, a training cohort with 2/3 (N=200) of the patients, and a validation cohort of 1/3 (N=98), proportional to death outcomes. With the data from the training group we estimated a multivariable Cox model with overall survival (OS) as dependent variable, and the eight referenced indices as explanatory variables. Any normal result was scored 0, and based on the estimated HR coefficient from the Cox model, a proportional weight score was given to each respective index variable in the calculation of the composite HCT Frailty Scale score. The HCT Frailty index was calculated using the following formula: 1.5 *CFS, +1*IADL, +1*GS, + 1.5*TUGT, + 1*SHR-Q, +1*Falls-Test, + 1.5 *Alb, + 2*CRP. As a result, the HCT Frailty Scale goes from 0 to 10.5. The values of the scale were grouped to determine the following three groups of patients: (a) Fit patent: scale score ≤1; (b) Pre-Frail patient: 1< scale score < 5.5; (c) Frail patient: scale score 5.5 (Figure 1). RESULTS Baseline characteristics of the training and validation cohort are shown in Figure 1. Of the 200 patients included in the training cohort, the median age was 58 years (range 19-76 years); 29 (15.85%) had a KPS between 70-80%; and 56 (30.11%) a HCT-CI >3. The elaborated HCT Frailty Scale classified the 200 patients as: (a) 70 (35%) fit patients with an estimated 1-y OS of 83.7%; (b) 97 (48.5%) pre-frail patients with a predicted 1-y OS of 75.6%; and (c) 33 (16.5%) frail patients with an estimated 1-y OS of 52.8%. Of the 33 frail patients, 54.8% had a KPS between 90-100% and 48.5% had an HCT-CI <3 and of the 70 fit patients, 4.8% had a KPS between 70-80% and 24.2% had an HCT-CI ≥ 3. These differences support the hypothesis that frailty does not necessarily correlate with performance and comorbidities. The predictive ability of the HCT Frailty Scale was validated in 98 patients included in the validation cohort. This scale identified (a) 33 (33.7%) fit patients with an expected 1-y OS of 90.3%, (b) 51 (52%) pre-frail patients with an expected 1-y OS of 69.5%, and (c) 14 (14%) frail patients with an estimated 1y OS of 46.2% (Figure 1). CONCLUSION The HCT Frailty Evaluation Scale has been specifically designed to be applied in routine clinical practice and to patients across all ages. The scale ranges from 0 to 10.5 and the score value is calculated as the weighted sum of values of eight indexes evaluated at first consultation. The proposed scale should be of utility to identify frail and pre-frail patients that may benefit from appropriate counselling pre-transplant and individualized interventions to reverse frailty syndrome prior to alloHCT. Figure 1 Figure 1. Disclosures Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Kim: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Paladin: Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria, Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company.

Association between frailty and mortality among patients with accidental hypothermia: a nationwide observational study in Japan

Background Frailty has been associated with a risk of adverse outcomes, and mortality in patients with various conditions. However, there have been few studies on whether or not frailty is associated with mortality in patients with accidental hypothermia (AH). In this study, we aim to determine this association in patients with AH using Japan’s nationwide registry data. Methods The data from the Hypothermia STUDY 2018&19, which included patients of ≥18 years of age with a body temperature of ≤35 °C, were obtained from a multicenter registry for AH conducted at 120 institutions throughout Japan, collected from December 2018 to February 2019 and December 2019 to February 2020. The clinical frailty scale (CFS) score was used to determine the presence and degree of frailty. The primary outcome was the comparison of mortality between the frail and non-frail patient groups. Results In total, 1363 patients were included in the study, of which 920 were eligible for the analysis. The 920 patients were divided into the frail patient group (N = 221) and non-frail patient group (N = 699). After 30-days of hospitalization, 32.6% of frail patients and 20.6% of non-frail patients had died (p < 0.001). Frail patients had a significantly higher risk of 90-day mortality (Hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.25–2.17; p < 0.001). Based on the Cox proportional hazards analysis using multiple imputation, after adjustment for age, potassium level, lactate level, pH value, sex, CPK level, heart rate, platelet count, location of hypothermia incidence, and rate of tracheal intubation, the HR was 1.69 (95% CI, 1.25–2.29; p < 0.001). Conclusions This study showed that frailty was associated with mortality in patients with AH. Preventive interventions for frailty may help to avoid death caused by AH.

Prognostic value of a comprehensive geriatric assessment for predicting one-year mortality in presumably frail patient with symptomatic aortic stenosis

IntroductionDespite of suffering a severe aortic stenosis, some patients are denied from either surgical or Transcatheter Aortic Valve Implantation (TAVI) therapy because of a frail condition. We aim to identify whether a comprehensive geriatric assessment (CGA) might be useful to predict prognosis of presumably frail patients with severe aortic stenosis.Material and methodsBetween March 2011 and July 2016, 818 patients were consecutively and prospectively enrolled. 161 had a CGA and were considered for analysis. Considering combined CGA and Heart team recommendations, 102 TAVI were performed (TAVI group) and 59 patients constituted the no TAVI group. Primary endpoint was all-cause mortality at one year.ResultsThere was no difference between the TAVI and the no TAVI groups considering morphometric data, cardiovascular risk factors or symptoms. The no TAVI group had higher surgical risk (logistic EuroSCORE1 33.4±17.8 vs. 22.7±14.9; p<0.001) and more moderate renal insufficiency (82% vs. 57%; p=0.001). One-year mortality was 16% in the TAVI group and 46% in the no TAVI group (p<0.001). Multivariate analysis revealed history of pulmonary edema, moderate renal failure, and not having a TAVI, to relate to 1-year mortality. There was an interaction of the Five-Times-Sit-to-Stand-Test (FTSST) upon the effect of TAVI on mortality (p=0.049), as FTSST was the only predictor for 1-year mortality in the no TAVI group (HR:0.18 95%CI 0.04–0.76; p=0.019).ConclusionsOne-year mortality was higher in geriatric-assessed frail patient who did not undergo TAVI. FTSST, which assesses patients’ mobility, was the only prognostic marker for 1-year mortality, on top of usual medical parameters.