Physiological Reserve Research Articles

Interplay And Causative Relationship Between Frailty And Atherosclerosis

Frailty syndrome is a complex condition with numerous contributing factors. It is characterized by a decline in physiological reserves and increased susceptibility to stress due to multi-system impairments. Commonly associated with aging, frailty can lead to adverse outcomes such as hospitalization, falls, and mortality. Cardiovascular diseases are recognized as a significant risk factor for frailty syndrome and frequently coexist in the elderly population. This review aims to explore the relationship between cardiovascular diseases and frailty syndrome. Research demonstrates that both acute and chronic cardiac conditions are prevalent among the risk factors for frailty. Cardiovascular diseases often manifest against the backdrop of atherosclerosis (AS) and are a leading cause of death in older adults. This review seeks to examine potential pathways through which cardiovascular events contribute to the development of frailty syndrome. Frail individuals often experience impaired physical function, significantly impacting their quality of life. Understanding the link between subclinical cardiovascular events and the pathogenesis of frailty syndrome is crucial for developing effective therapeutic interventions. Investigating how cardiovascular events influence the progression of frailty can provide valuable insights into improving clinical outcomes for frail patients.

Frailty in the context of kidney transplantation.

Frailty, defined as an inappropriate response to stressful situations due to the loss of physiological reserve, was initially described in the elderly population, but is currently being identified in younger populations with chronic diseases, such as chronic kidney disease. It is estimated that about 20% of patients are frail at the time of kidney transplantation (KT), and there is great interest in its potential predictive value for unfavorable outcomes. A significant body of evidence has been generated; however, several areas still remain to be further explored. The pathogenesis is poorly understood and limited to the extrapolation of findings from other populations. Most studies are observational, involving patients on the waiting list or post-KT, and there is a scarcity of data on long-term evolution and possible interventions. We reviewed studies, including those with Brazilian populations, assessing frailty in the pre- and post-KT phases, exploring pathophysiology, associated factors, diagnostic challenges, and associated outcomes, in an attempt to provide a basis for future interventions.

The relationship between self-perceived fatigue, muscle endurance, and circulating markers of inflammation in participants of the Copenhagen aging and Midlife Biobank (CAMB)

BackgroundFatigue, low muscle endurance, muscle weakness and low-grade inflammation are strongly related to frailty at higher age. When signs of self-perceived fatigue and low muscle endurance are interrelated with low-grade inflammation at midlife, they might be used as early markers for frailty. This study investigated whether the interrelationships among self-perceived fatigue, muscle endurance and inflammation can be observed at midlife.MethodsA total of 965 participants of the Copenhagen Aging and Midlife Biobank (aged 52 ± 4 years, 536 males, 426 females) were assessed for self-perceived fatigue (20-item multidimensional fatigue inventory), muscle endurance (grip work), circulating markers of inflammation (hsCRP, IL-6, IL-10, TNF-alpha and IFN-γ), daily physical activity (PAS-2), body composition (%body fat assessed by bio-impedance) and self-reported health status. Participants were categorised (correcting for age and gender) according to high fatigue and/or low muscle endurance, differences in inflammatory profile between fatigue categories were assessed by ANCOVA (corrected for PAS-2, %body fat and presence of inflammatory conditions).ResultsOverall, muscle endurance, fatigue and inflammatory markers were significantly interrelated. Higher levels of hsCRP (p < 0.001), IL-6 (p < 0.001), IL-10 (p = 0.035) and TNF-alpha (p = 0.028) were observed in participants presenting both low muscle endurance and high fatigue. IFN-γ was highest in those with high fatigue but normal muscle endurance (p = 0.015).ConclusionsMiddle-aged participants with higher fatigue in combination with low muscle endurance show higher levels of inflammation, independently from physical activity, body fat and inflammatory pathology. The underlying mechanisms should be identified and future studies should also investigate whether these individuals show early signs of reduced physiological reserve capacity, which in later life come to full expression by means of frailty.

Multidisciplinary prehabilitation to improve frailty and functional capacity in high-risk elective surgical patients: a retrospective pilot study

BackgroundFrailty is associated with worse outcomes and higher healthcare costs. The long waiting time for surgery is a potential ‘teachable’ moment. We examined the feasibility and safety of a pilot prehabilitation programme on high-risk frail patients undergoing major elective surgery.MethodsA single-centre, retrospective pilot study (Dec 2020–Nov 2021) on a one-stop prehabilitation programme (structured exercise training, nutritional counselling/therapy, and psychological support) in collaboration with geriatricians and allied health professionals. At least 4 weeks before surgery, patients at high risk of frailty or malnutrition, or undergoing major hepatectomy, esophagectomy, pancreaticoduodenectomy, or radical cystectomy, were referred for prehabilitation (2–3 sessions/week). The primary outcomes were the feasibility and safety of prehabilitation. The secondary outcomes were changes in functional, emotional, and nutritional status and days alive and at home within 30 days after surgery (DAH30) associated with prehabilitation.ResultsOver a 12-month period, 72 out of 111 patients (64.9%) from the Perioperative Medicine Clinic were eligible for prehabilitation, of which 54 (75%) were recruited. The mean (standard deviation) age was 71.9 (6.9) years. The adherence rate to 3 weeks of prehabilitation was high in 52 (96.3%) participants. Prehabilitation improved exercise capacity (P = 0.08), enhanced some functional mobility measures (P = 0.02), and increased nutritional energy (P = 0.04) and protein intakes (P < 0.01). However, prehabilitation-related changes in muscle strength, cognitive function, and emotional resilience were minimal. The median (interquatile range) DAH30 was 19 (14–23) days. No adverse events were reported.ConclusionsThis outpatient-based, one-stop multidisciplinary prehabilitation programme was feasible, safe, and improved several measures of patient’s physiological reserve and functional capacity.Clinical trial registrationNCT05668221.

1849 Implementing a comprehensive geriatric assessment (CGA) in older adults presenting to a district general emergency department

Abstract Introduction Frailty is the concept of increasing vulnerability to minor stressors in the context of a reduction in physiological reserves (Clegg et Al. The Lancet 2013, Volume 381, pages 752-762). It affects 10% of people presenting to Emergency departments (ED) and around 30% of inpatients in acute medical units (NHS England and NHS Improvements. 2019). Implementing a CGA is known to result in a significant increase in your likelihood of being alive and in your own home at 6 months (Ellis et Al. BMJ 2013). Aims To implement an ED in reach frailty service with the goal of performing a CGA at the earliest opportunity. Methods We undertook a 3-week pilot with a small team comprising a consultant, frailty ACP, SHO and geriatric registrar. The team were based in ED and worked alongside the existing ED navigator team and in conjunction with various community teams. Data was collected assessing completion of the usual domains within the CGA and discharge data. Results 62 patients were seen in total. Mean age was 82.4 years with a mean CFS of 5. Each patient received a CGA. 9/62 (15%) of patients were discharged on the same day. 15/53 (28%) were discharged within 72 hours of admission. Other notable results include: 100% completion of 4AT and 70 medications de-prescribed. Feedback from patient and relatives in addition to ED and AMU doctors was extremely positive. Conclusion We demonstrated that performing a CGA in ED resulted in higher numbers of patients being discharged on the same day or within 72 hours of admission. We were able to demonstrate a significant increase in assessment of delirium allowing earlier detection and a much higher rate of deprescribing with significant benefits for both patient and the trust.

Asthenic disorders correction with Recognan

Asthenia, asthenic syndrome, asthenic condition, asthenic reaction, asthenic disorders are terms that describe the state of «impotence». Fatigue that occurs against the background of habitual physical or intellectual stress for a person, and persists after rest, is asthenia. For people of the older age group, the term senile asthenia syndrome is used. Asthenia manifests itself with increased fatigue and exhaustion, mood instability, increased irritability, sleep disorders. Asthenic conditions manifest themselves along with a decrease in physical activity, increased cognitive and mental fatigue. Asthenic syndrome (AS) are considered as an integral part of cardiovascular diseases (CVD), as one of the manifestations of cerebrovascular pathology. Senile asthenia syndrome (SAS) is a geriatric syndrome characterized by an age-associated decrease in the physiological reserve and functions of many body systems, including cognitive functions. One of the drugs that has a positive effect on the severity of AS and improves the state of cognitive functions is the domestic drug Recognan (citicoline). The effectiveness of Recognan in the treatment of AS in patients with CVD, SAS, and post-COVID asthenia has been shown. It is recommended to prescribe Recognan orally at 500 mg / day for 30 days. Recognan has a nootropic and antiasthenic effect.

Strategies to Assess and Manage Frailty among Patients Diagnosed with Primary Malignant Brain Tumors.

Frailty refers to a biologic process that results in reduced physiologic and functional reserve. Patients diagnosed with primary malignant brain tumors experience high symptom burden from tumor and tumor-directed treatments that, coupled with previous comorbidities, may contribute to frailty. Within the primary malignant brain tumor population, frailty is known to associate with mortality, higher healthcare utilization, and increased risk of postoperative complications. As such, methods to assess and manage frailty are paramount. However, there is currently no clear consensus on how to best assess and manage frailty throughout the entirety of the disease trajectory. Given the association between frailty and health outcomes, more research is needed to determine best practice protocols for the assessment and management of frailty among patients diagnosed with primary malignant brain tumors.

Predictors of Per-Intubation Cardiac Arrest in Pediatrics Patients Presenting to the Emergency Department

INTRODUCTION: Airway management is one of the vital resuscitative procedures undertaken in many critically ill pediatric patients presenting for emergency care. Around (2–33/10,000) of all pediatric patients presenting to the emergency department (ED) require airway protection for various conditions, such as respiratory failure, airway protection, and cardiac arrest 1-3. In children, airway management demands great caution because of their age-related differences in anatomical and physiological characteristics and limited physiological reserves. Rapid sequence intubation (RSI) has become the standard technique to facilitate pediatric emergency airway management. AIM OF STUDY: To determine the risk factors associated with peri-intubation cardiac arrest in pediatric patients presenting to the emergency department. RESULTS: Total 125 patients were recruited with case to control ratio of 1:4. Data was analyzed for demographic, examination, level of training, drug and outcome variables. The median age group was 18months. Among patients who underwent PICA 40% achieved the ROSC. The most common cardiacrhythm was bradycardia. The patients who underwent PICA had raised heart rate and low blood pressure. The hypoxia was found to be significant contributor to PICA. ROC curve applied to values with significant result after regression analysis. CONCLUSION: The major contributor to peri-intubation cardiac arrest is hypoxia OR 8.96 [2.52 -31.88]. Level of training had no significant relation to PICA. SI and MSI were strongly associated with PICA with OR of 3.78 [1.06 -13.52] &amp; 4.93 [1.09 -22.24] respectively.

Mental health and frailty in people with multiple sclerosis: unraveling a complex relationship.

People with multiple sclerosis (MS) have up to a 15 times higher risk of being frail compared to age-matched individuals without MS. Frailty is a biological syndrome of decreased physiological reserve and resilience that increases the vulnerability to adverse clinical outcomes and leads to a lower quality of life. Recent studies have begun investigating frailty in the context of MS, highlighting several associations between frailty and adverse events, such as falls, and common MS-related symptoms involving the physical health domain, such as walking and sleeping problems. However, there is a critical knowledge gap regarding the relationship between mental health and frailty in people with MS. This mini-review article aimed to shed light on the potential relationships between MS, frailty, and mental health. Despite the dearth of studies on this topic, indirect evidence strongly suggests that the association between frailty and mental health in people with MS is likely bidirectional in nature. Specifically, mental health disorders such as depression and anxiety may be involved in the etiology of frailty in people with MS. However, they could also be exacerbated by the detrimental effects of frailty on overall health. The complex relationship between frailty and mental health in MS underscores the multifaceted challenges people with MS face. Conducting further research to untangle such a relationship is critical to developing early detection and intervention strategies for improving well-being and medical outcomes in people with MS.

Sarcopenia and frailty in inflammatory bowel disease: Emerging concepts and evidence.

Sarcopenia is a condition marked by progressive loss of skeletal muscle mass and function while frailty is a multidimensional concept characterized by diminished physiological reserve and increased vulnerability to stressors. Both of these were previously considered as related to aging and shown to impact the quality of life and carry prognostic significance. Emerging data show that both sarcopenia and frailty carry similar relevance in chronic illness. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and malnourishment, both of which contribute to the development of sarcopenia by increasing protein breakdown and reducing protein synthesis. The coexistence of frailty further compounds the clinical complexity of IBD patients. Published evidence suggests a bidirectional association with IBD contributing to muscle wasting, while the resultant sarcopenia and frailty could further exacerbate the disease course. Sarcopenia and frailty are independently associated with adverse outcomes, including hospitalizations, increased surgical interventions, and surgical complications. As therapeutic strategies for IBD evolve, understanding the nuanced relationship between inflammatory bowel disease, sarcopenia, and frailty is crucial for devising holistic management. Comprehensive care should encompass not only disease-modifying therapies but also interventions targeting frailty and sarcopenia, as they have been shown to have a significant impact not only on the disease course but also on the quality of life. Future research could focus on further elucidating underlying mechanisms, simple screening strategies, and developing targeted interventions to improve the overall quality of life for individuals grappling with the complex interplay of IBD, sarcopenia, and frailty.

Hypertension in frail older adults: current perspectives.

Hypertension is one of the most common chronic diseases in older people, and the prevalence is on the rise as the global population ages. Hypertension is closely associated with many adverse health outcomes, including cardiovascular disease, chronic kidney disease and mortality, which poses a substantial threat to global public health. Reasonable blood pressure (BP) management is very important for reducing the occurrence of adverse events. Frailty is an age-related geriatric syndrome, characterized by decreased physiological reserves of multiple organs and systems and increased sensitivity to stressors, which increases the risk of falls, hospitalization, fractures, and mortality in older people. With the aging of the global population and the important impact of frailty on clinical practice, frailty has attracted increasing attention in recent years. In older people, frailty and hypertension often coexist. Frailty has a negative impact on BP management and the prognosis of older hypertensive patients, while hypertension may increase the risk of frailty in older people. However, the causal relationship between frailty and hypertension remains unclear, and there is a paucity of research regarding the efficacious management of hypertension in frail elderly patients. The management of hypertension in frail elderly patients still faces significant challenges. The benefits of treatment, the optimal BP target, and the choice of antihypertensive drugs for older hypertensive patients with frailty remain subjects of ongoing debate. This review provides a brief overview of hypertension in frail older adults, especially for the management of BP in this population, which may help in offering valuable ideas for future research in this field.

Machine learning approaches for predicting frailty base on multimorbidities in US adults using NHANES data (1999–2018)

BackgroundThe global increase in an aging population has led to more common age-related health challenges, particularly multimorbidity and frailty, but there is a significant gap. MethodsThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (1999–2018). The association between age and frailty was assessed using a restricted cubic spline (RCS) model, while weighted adjusted multivariable logistic regression evaluated the effect of diseases to frailty. And in machine learning process, feature selection for the frailty prediction model involved three algorithms. The model's performance was optimized using nested cross-validation and tested with various algorithms including decision tree, Logistic Regression, k-Nearest Neighbor, Random Forest, Recursive Partitioning and Regression Trees, and eXtreme Gradient Boosting (XGBoost). We used areas under the receiver operating characteristic curve (AUC) and area under the precision-recall curve (AU-PRC) to evaluate six algorithms, select the optimal model, and test the discrimination and consistency of the optimal model. ResultsThe study included 46,187 participants, with 6,009 cases of frailty. RCS analysis showed a non-linear association between age and frailty, with a turning point at 49 years. Key impacting variables identified are Anemia, Arthritis, Diabetes Mellitus, Coronary Heart Disease, and Hypertension. In the machine learning process, we selected the optimal data set by feature selection, including 13 variables. Through nested cross-validation, a total of 31,900 models were built using 6 algorithms. And the XGBoost model showed the highest performance (AUC = 0.8828 and AU-PRC = 0.624), and clear proficiency in both discrimination and calibration. ConclusionsWe found 49 years maintain the balance of physiological reserve and external aggression. In addition, chronic diseases are trigger factor of frailty, while acute diseases are contributing factor that exacerbates the body's rapid decline. Last, the XGBoost frailty prediction model, with its simplicity, high performance and high clinical value holds potential for clinical application.

An IT-supported multidimensional approach for frailty screening in community-dwelling older adults

Introduction: Frailty in older adults is characterised by a dynamic state of vulnerability with weakness and reduced physiological reserve leading to an increased risk of worsening in quality of life, falls, institutionalisation, disability and death [1]. The COVID-19 pandemic is an example of how an infectious hit can determine an increased mortality especially among older and vulnerable population subgroups [2], as well as a deterioration in their quality of life due to loneliness and limited access to health and social services. Frailty syndrome is a complex interplay between several factors, including, but not limited to, natural physiological changes in ageing, multi-morbidities, malnutrition, living environment, genetics and lifestyle [3]. Early screening for frailty risk factors in the community-dwelling older adult population allows preventive interventions on the clinical and social determinants of frailty, avoiding adverse events and contributing to improve the resilience of health care systems.&#x0D; Method: Programma Mattone Internazionale Salute (ProMIS), the Italian Ministry of Health's programme for innovation of regional health systems [4], built up a working group (WG) on Frailty, including doctors, nurses, home care professionals, physiotherapists, pharmacists, psychologists, dieticians, social workers, physical trainers and policy makers, to develop a proactive and integrated approach to detect frailty and its risk factors in community-dwelling older adult population.&#x0D; Results: The participatory activity of ProMIS’ WG led to the identification of an integrated approach aimed to connect the SUNFRAIL tool for the early identification of frailty in the over-65 population [5] to other in-depth scales for the assessment of specific dimensions of frailty, guiding subsequent diagnostic assessments for health promotion, disease prevention and intervention. An IT tool was developed for data collection, SUNFRAIL+, which includes, in addition to SUNFRAIL tools, the validated scales for screening the nine domains of frailty, which automatically generates alerts, thanks to which targeted interventions will be activated in the compromised domains. A national multi-centre observational study protocol has been designed to validate the approach by assessing the impact of early, integrated, and multi-professional care on the quality of life of the community-dwelling older adult population and the professional’s satisfaction.&#x0D; Conclusion and discussion: The study design builds on the tool developed by the SUNFRAIL EU project [6], and provides the background for bridging multidimensional interventions to prevent frailty and mitigate its consequences on quality of life and functional ability in community-dwelling older adults, exploiting available services in the different health care services. The study will also provide the information needed to design a logical model integrating coherent interventions in the framework of specific frailty domains.

Preoperative Frailty and Malnutrition in Surgical Oncology Patients Predicts Higher Postoperative Adverse Events and Worse Survival: Results of a Blinded, Prospective Trial.

Frailty, a multidimensional state leading to reduced physiologic reserve, is associated with worse postoperative outcomes. Despite the availability of various frailty tools, surgeons often make subjective assessments of patients' ability to tolerate surgery. The Risk Analysis Index (RAI) is a validated preoperative frailty assessment tool that has not been studied in cancer patients with plans for curative-intent surgery. In this prospective, surgeon-blinded study, patients who had abdominal malignancy with plans for resection underwent preoperative frailty assessment with the RAI and nutrition assessment by measurement of albumin, prealbumin, and C-reactive protein (CRP). Postoperative outcomes and survival were assessed. The study included 220 patients, 158 (72%) of whom were considered frail (RAI ≥21). Frail patients were more likely to be readmitted within 30 and 90 days, (16% vs. 3% [P = 0.006] and 16% vs. 5% [P = 0.025], respectively). Patients with abnormal CRP, prealbumin, and albumin experienced higher rates of unplanned intensive care unit admission (CRP [27% vs. 8%; P < 0.001], albumin [30% vs. 10%; P < 0.001], prealbumin [29% vs. 9%; P < 0.001]) and increased postoperative mortality at 90 and 180 days. Survival was similar for frail and non-frail patients. In the multivariate analysis, frailty remained an independent risk factor for readmission (hazard ratio, 5.58; 95% confidence interval, 1.39-22.15; P = 0.015). In the post hoc analysis using the pre-cancer RAI score, the postoperative outcomes did not differ between the frail and non-frail patients. In conjunction with preoperative markers of nutrition, the RAI may be used to identify patients who may benefit from additional preoperative risk stratification and increased postoperative follow-up evaluation.

Frailty as a Prognostic Indicator in Lung Transplantation: A Comprehensive Analysis

Introduction: Frailty is a complex pathobiological process characterized by diminished physiological reserve and increased vulnerability to stressors, which has been associated with unfavorable outcomes before and after lung transplantation. Methods: We undertook an extensive narrative review, encompassing a thorough exploration of original papers, observational studies, case reports, and meta-analyses published between 1990 and July 2023, in various databases, including PubMed, Embase, Cochrane Library, Wiley Online Library databases, and Google Scholar. The search terms [frailty] AND [lung transplant] were utilized. Additionally, the reference lists of retrieved articles were examined. Inclusion criteria comprised studies written in English and involving human subjects. The identified studies were categorized into pre-transplant and post-transplant populations, and the measurement tools used to assess frailty were analyzed, along with the clinical implications reported in the studies. Results: From 1 January 1990 to 1 July 2023, a total of 10 studies on frailty and lung transplantation were identified through online sources and bibliographic searches, involving a total of 2759 patients. Among these studies, six focused on the pre-transplant population, while four examined the post-transplant population. The Fried Frailty Phenotype (FFP) and the Short Physical Performance Battery (SPPB) were the most employed tools for measuring frailty. A table presents additional frailty assessment instruments and the clinical implications described in the studies. Conclusions: Frailty is prevalent both in patients with end-stage respiratory diseases awaiting lung transplantation and in postoperative lung transplant recipients. Most transplant centers recognize the value of assessing frailty in the evaluation of potential candidates for lung transplantation. Frailty has been shown to impact mortality on the waitlist and in the post-transplant period. However, the most effective methods for measuring frailty in lung transplant candidates and recipients have yet to be determined. Strategies to reverse frailty are available and show promising results on outcomes.

Fragility and its relationship with geriatric syndromes in a mexican population of elderly adults in a third‐level hospital

AbstractBackgroundFrailty refers a term which describes general state of health that is characterized by an increased susceptibility or vulnerability for stressors as a consequence a deterioration of physiological reserves. Frailty have been associated to multiple Geriatric syndromes, higher rates on mortality and increased risks for poor outcomes, including Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI), which are conditions that may be common in older adults.MethodThis report is a secondary analysis from a transversal study, the inclusion criteria include adults from 60 or older, who complete evaluations at the baseline in a from a dementia clinic at a tertiary care center in Mexico. We exclude pre‐fragile and robust participants at the baseline, the analytical simple comprised 700 older adults. Frailty was established using the FRAIL criteria the presence of 3 or more remaining criteria was considered frailty. Sociodemographic variables, comorbidities, and geriatric syndromes were considered for the analysis.ResultA total of 700 older adults were evaluated and 242 (34.5%) were diagnose with Frailty. Comorbidities such as diabetes (41.7%), high blood pressure (64%) and osteoarthritis (50%) were prevalent with frailty. Female sex (63.6%) and marital status marriage (55%) were prevalent with frailty. The incidence of mild dementia was 35.1% and 28.9% for mild cognitive impairment. Multiple logistic regression was performed finding an OR (95% CI) P &lt;.001 in the association of frail patients in the 60‐70 age group, the association of the female sex with frailty present in OR (95% CI). P .023 and being married OR (95% CI) P &lt; .001.ConclusionIn Mexican older adults from the clinical population, the results demonstrated that frailty was associated with mild cognitive impairment and mild dementia as well as female sex, married marital status, and age. It would be necessary to compare with other groups without frailty to demonstrate the consistency of these findings as potential risk factors.

Commentary: Key Aspects of Multimodal Prehabilitation in Surgical Patients With Cancer. A Practical Approach to Integrating Resistance Exercise Programs.

Surgical prehabilitation aims to optimise patients' physiological reserves to better withstand the stress of surgery, reduce the risk of postoperative complications, and promote a faster and optimal recovery. The purpose of this commentary is to outline the key aspects of prehabilitation before surgery for cancer which seem to impact its effectiveness and wider implementation. Particular attention is paid to the role and integration of resistance training programmes as a key component of multimodal prehabilitation for patients with cancer. We firstly analyse some of the barriers currently hindering the implementation of prehabilitation programmes in the National Health Service (United Kingdom). Later, we describe essential aspects of resistance training design, such as exercise modality and order execution, volume and intensity, rest periods between sets or exercises, and workout frequency. Furthermore, we propose a methodology to use the perception of effort to control patients' progression during a prehabilitation programme.

Frailty Predicts Worse Outcomes in Tumor Lysis Syndrome

DISCUSSION Tumor lysis syndrome (TLS) is a potentially life-threatening complication that occurs in the setting of rapid tumor cell destruction. The Hospital Frailty Risk Score (HFRS) is a valuable tool to identify frailty in older individuals, signifying a decline in physiological reserves and coping ability due to age-related deterioration, and it has gained recognition as a crucial factor linked to adverse events, including mortality, hospitalization, and diminished functional outcomes. We aimed to assess the impact of HFRS on individuals admitted with a primary diagnosis of TLS. Using weighted data from the Nationwide Inpatient Sample (NIS) database from 2016 to 2020, we assessed the outcomes (mortality, hospital utilization, total healthcare charges, complications) of individuals admitted with a primary diagnosis of TLS stratified by the presence and absence of Frailty (determined by the combination of 109 ICD-10 codes each with a different score) (table 1). Baseline characteristics were analyzed using T-test and Chi-Square, and a multivariate regression analysis was used to estimate outcomes between races, adjusted for patient and hospital confounders. Data analysis was performed using STATA® Version 17.0/SE Software, with statistical significance set at p &amp;lt; 0.05. A total of 4,340 were admitted with a primary diagnosis of TLS from 2016 to 2020, among these, we selected 1,330 admissions aged 75 years or older; these admissions included 59% (N=785) with frailty, and 41% (N=545) without frailty. Frailty was associated with increased length of stay (adjusted mean difference (aMD) = 2.5 days, 95%CI: 1.2 - 3.8 days), and total healthcare expenditures (aMD = 22,541 U.S. dollars (USD), 95%CI: 2,175 - 42,908 USD). Pertaining to the outcomes, a 9- fold increase in the odds of mortality were noted among individuals with frailty, as opposed to those without frailty (adjusted Odds Ratio (aOR) = 8.93, 95%CI: 1.79 - 44.74). Our study depicts the significant impact of frailty on individuals hospitalized with TLS, revealing associations with elevated mortality rates, prolonged length of hospital stay, and increased healthcare costs. Considering a considerable portion of cancer patients fall within the elderly demographic and often present with multiple comorbidities, the Hospital Frailty Risk Score (HFRS) is a potential valuable tool for assessing the appropriateness of chemotherapy in conjunction with other scores like the Eastern Cooperative Oncology Group (ECOG). Moreover, the HFRS may aid in prognosticating disease outcomes, offering clinicians valuable insights to inform treatment decisions and improve patient care.

Impact of COVID-19 Pandemic on Overall Survival in Acute Myeloid Leukemia: A Comprehensive Cancer Center Experience of 627 Patients

Background: The COVID-19 pandemic impacted cancer care nationwide. Challenges with frequent clinic visits for lab draws, administration of multi-agent chemotherapy regimens, and scarcity of supportive blood products disrupted effective health care delivery. The magnitude of these factors on the survival of patients diagnosed with acute myeloid leukemia (AML) during the pandemic is incompletely described. Methods: We included 627 patients aged ≥18 years with AML treated at VCU Massey Comprehensive Cancer Center from January 1, 2013 to December 31, 2022; we recorded baseline demographics, molecular profiles, induction regimens, and survival data. We defined the pandemic era as March 7, 2020 (coinciding with the first confirmed case in our region) to July 1, 2021 (routine and widespread vaccination available). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. ECOG and Charlson comorbidity index (CCI) scores were compared using the Mann-Whitney test; we used the D'Agostino &amp; Pearson method for normality testing. Results: The median age of patients who received intensive chemotherapy (7+3, CPX-351, FLAG-IDA, MEC, or HAM) in the COVID-19 pandemic cohort was 60 years (range, 28.5-69.6) vs 58 years (range, 19.6-81.4) for the non-COVID-19 cohort (p = 0.932). The median ECOG performance status in both cohorts was 1 (range, 0-4, p = 0.658). The median Charlson comorbidity index (CCI) score for patients for both groups was 4 (range, 0-9 vs 2-9, p = 0.909). Patients who were initiated on lower-intensity therapies (e.g., a hypomethylating agent with or without venetoclax) during the COVID-19 pandemic had a median age of 75 (range, 61.9-85.1) years vs 73 (range, 26.1-92.0) years in the non-COVID-19 cohort (p=0.438). The median ECOG performance status for the COVID-19 cohort was 2 (range, 0-3) vs 1 (range, 0-4) for the non-COVID-19 cohort (p=0.005). CCI score for both groups was 6 (range, 4-12 vs 2-14, p=0.789). We then compared the mOS between the COVID-19 and non-COVID-19 eras for both intensive and non-intensive treatment cohorts. For patients treated with intensive chemotherapy during the pandemic, the mOS was 25.1 months in the COVID-19 cohort vs 18.0 months (p = 0.173) in the non-COVID-19 cohort. For patients treated with non-intensive regimens, mOS was 6.6 months in the COVID-19 cohort vs 6.0 months in the non-COVID-19 cohort (p = 0.963). Patients with relapsed disease who were retreated with intensive chemotherapy during the COVID-19 pandemic had a mOS of 6.5 months compared to 8.2 months (p = 0.094) in the non-COVID-19 cohort. Relapsed patients in the lower-intensity COVID-19 cohort had a significantly shorter mOS of 1.8 months compared to 5.2 months in the non-COVID-19 cohort (p = 0.005). Regardless of therapy, the mOS was shorter in the COVID-19 cohort at 11.0 months compared to 13.4 months in the non-COVID-19 cohort (p = 0.191). Relapsed or refractory patients in the COVID-19 cohort had significantly shorter mOS at 5.8 months compared to 8.0 months in the non-COVID-19 cohort (p = 0.019). Discussion: The median overall survival appears shorter for patients diagnosed with AML during the COVID-19 pandemic. Patients with relapsed or refractory AML appeared to have significantly worse overall survival during the COVID-19 pandemic, particularly with lower-intensity therapies. Patients treated with less-intensive regimens are generally older with increased frailty, raising concern for lack of physiologic reserve. These results convey a lesson in preparation for future healthcare crises.

Axicabtagene Ciloleucel in Patients Aged 75 and Older: A Retrospective Cohort Study

Background The treatment of older patients with relapsed/refractory (R/R) aggressive non-Hodgkin B-cell lymphomas (NHL) remains a significant clinical challenge. Chimeric antigen receptor T-cell (CAR-T) therapy represents a potentially curative option, but elderly patients remain underrepresented in relevant clinical trials, and less is known about the safety of CAR-T among patients older than 75 years. Toxicities including cytokine release syndrome (CRS), neurotoxicity (ICANS), arrhythmias, renal failure, and cytopenias may pose higher risk in elderly patients with comorbidities and decreased physiologic reserve compared to younger CAR-T recipients. We sought to characterize outcomes and toxicities of axicabtagene ciloleucel (axi-cel) in a cohort of patients aged ≥ 75 years. Methods This was a retrospective analysis of consecutive patients aged ≥ 75 years with R/R NHL who received axi-cel at New York-Presbyterian/Weill Cornell Medical Center. Data collected included patient characteristics and outcomes including response rates, event-free and overall survival, rates of CRS, ICANS, arrhythmias and severe cytopenias, and length of hospital stay. CRS and ICANS severity were graded following the ASTCT consensus criteria. Cytopenias were graded as per NCI-CTCAE v5.0. Event free survival (EFS) was defined as time to disease progression or death. Results We identified 15 patients with a median age of 78 (range 75-87) years; 6 (40%) were ≥ 80 years of age. 14 patients had a diagnosis of large B-cell lymphoma and 1 had multiply relapsed follicular lymphoma. Ten patients (67%) had received 3 or more prior lines of therapy. Additional baseline characteristics are summarized in Table 1. Among 10 patients (67%) who developed CRS of any grade, only 1 (7%) experienced grade ≥3 CRS; this CRS event was fatal. Five (33%) patients developed ICANS with only 1 patient (7%) developing grade ≥3 ICANS. Two (13%) patients and 10 (67%) patients developed grades 3 and 4 cytopenias within 30 days of infusion, respectively. Four (27%) patients required blood or platelet transfusions within 100 days of infusion. Febrile neutropenia was seen in 8 (53%) patients, and 8 patients had culture or PCR-verified bacterial (33%), viral (40%), or fungal (7%) infections. Only 1 (7%) patient developed a new abnormality on EKG within 30 days of infusion (right ventricular conduction delay). Median length of inpatient stay was 17 days (range 13-35), and 2 (13%) required re-hospitalization within 100 days of infusion. Overall and complete response rates at 100 days post-infusion were 13 (86%) and 11 (73%), respectively. At one year, overall and event-free survival were 72.2% (95% CI: 54.4-99.6%) and 53.3% (95% CI: 33.2%-85.6%), respectively. The median overall survival was 30.8 months with a median follow-up of 21.4 months. One patient experienced treatment-related mortality due to CRS, and 5 (33%) had subsequent disease relapse. Conclusion These results suggest that axi-cel is an effective and well-tolerated treatment for patients age ≥ 75 with R/R NHL. Only 1/15 patients developed grade ≥3 CRS or ICANS which is comparable to reported rates of toxicities in younger patients. Although multiple studies have identified cytopenias and cardiac arrhythmias as major CAR-T toxicities, a minority of our cohort required transfusions, and none developed life-threatening arrhythmias. OS and EFS were also comparable to real-world experience seen in younger patients. This study may be limited by the selection of a relatively fit population of elderly patients; however, the median Karnofsky Performance Score was 80 and ranged as low as 60. Overall, these findings show that axi-cel may be an appropriate strategy for relapsed aggressive NHL in carefully selected patients in their eighth and even ninth decades of life.