Multidimensional Geriatric Assessment Research Articles

Physical performance strongly predicts all-cause mortality risk in a real-world population of older diabetic patients: machine learning approach for mortality risk stratification.

Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning. A retrospective longitudinal study was conducted in a real-world sample of older diabetic patients afferent to the outpatient facilities of the Diabetology Unit of the IRCCS INRCA Hospital of Ancona (Italy). A total of 1,001 T2D patients aged more than 70 years were consecutively evaluated by a multidimensional geriatric assessment, including physical performance evaluated using the Short Physical Performance Battery (SPPB). The mortality was assessed during a 5-year follow-up. We used the automatic machine-learning (AutoML) JADBio platform to identify parsimonious mathematical models for risk stratification. Of 977 subjects included in the T2D cohort, the mean age was 76.5 (SD: 4.5) years and 454 (46.5%) were men. The mean follow-up time was 53.3 (SD:15.8) months, and 209 (21.4%) patients died by the end of the follow-up. The JADBio AutoML final model included age, sex, SPPB, chronic kidney disease, myocardial ischemia, peripheral artery disease, neuropathy, and myocardial infarction. The bootstrap-corrected concordance index (c-index) for the final model was 0.726 (95% CI: 0.687-0.763) with SPPB ranked as the most important predictor. Based on the penalized Cox regression model, the risk of death per unit of time for a subject with an SPPB score lower than five points was 3.35 times that for a subject with a score higher than eight points (P-value <0.001). Assessment of physical performance needs to be implemented in clinical practice for risk stratification of T2D older patients.

Prognostic effect of systematic geriatric assessment on patients with acute heart failure.

Frailty and dependence are frequent in patients admitted for acute heart failure (AHF), but their prognostic significance is unknown, especially in young adults. We aimed to study in adults admitted for AHF, regardless of age, the effect of frailty and dependence on the incidence of mortality and a combined event of mortality, readmissions for AHF, and visits to the emergency room (ER) for AHF at 1 and 6months. We designed a prospective cohort study by including all the patients with AHF admitted in our Cardiology Department from July 2020 through May 2021. A multidimensional geriatric assessment was performed during the admission. We clinically followed up the patients 6months after discharge. We enrolled 202 patients. The mean age was 73±12.32years, and 100 (49.5%) of the patients were elderly (>75years). Just 78 patients (38.6%) were women, and 100 (49.5%) had previous HF. Frailty (FRAIL≥3) was observed in 68 (33.7%) patients (mean FRAIL score: 1.88±1.48). Dependence (Barthel<100) was observed in 65 (32.2%) patients (mean Barthel index: 94.38±11.21). Frailty and dependence showed a significant association with both prognostic events at 1 and 6months. In the multivariable analysis, frailty was associated with higher mortality at 1month [hazard ratio (HR) 12.61, 95% confidence interval (CI) 1.57-101.47, P=0.017] but not at 6months (HR 2.25, 95% CI 0.61-8.26, P=0.224) or with the combined endpoint at neither 1month (HR 1.64, 95% CI 0.54-5.03, P=0.384) nor 6months (HR 1.35, 95% CI 0.75-2.46, P=0.320). Dependence was related to higher mortality at 1month (HR 13.04, 95% CI 1.62-104.75, P=0.016) and 6months (HR 7.18, 95% CI 1.99-25.86, P=0.003) and to higher incidence of the combined event at 1month (HR 5.93, 95% CI 1.63-21.50, P=0.007) and 6months (HR 2.62, 95% CI 1.49-4.61, P=0.001). In AHF patients, frailty and dependence implied a worse prognosis, rising mortality, readmissions, and ER visits for AHF.

1709 Comparative performance of six multimorbidity indices to discriminate intrinsic capacity impairments among older adults

Abstract Introduction Optimal intrinsic capacity (IC) is crucial for preserving the functional abilities of older adults. The presence of multimorbidity is closely associated with IC impairments. Various multimorbidity indices have been developed for diverse health outcomes. This study aimed to compare the performance of six commonly used multimorbidity indices to discriminate IC impairments among community-dwelling older adults. Method We used data from a multidimensional geriatric assessment program including 627 community-dwelling older adults in five cities of Hunan, China. Six multimorbidity indices were extracted from the data, including disease counts, Functional Comorbidity Index (FCI), the Deyo Charlson comorbidity index, two indices (total score and comorbidity index) derived from the Cumulative Illness Rating Scale-Geriatric (CIRS-G), and medication counts. The IC was measured with five individual domains, i.e., locomotion, vitality, sensory, cognition, and psychological capacity. Individuals were regarded as having IC impairments if they had impairments in one or more domains. Associations between multimorbidity indices and IC impairments were examined using logistic regression analyses. The discriminative ability of multimorbidity indices for IC impairments was compared using the c-statistics. Results A total of 374 (59.6%) participants had IC impairments. All multimorbidity indices were significantly associated with IC impairments after adjusting for confounding factors. All indices showed acceptable discriminative power (c-statistic ranged from 0.711 to 0.759) for IC impairments. The comorbidity index derived from CIRS-G resulted in the highest c-statistic, followed by the total score of CIRS-G and FCI. Conclusions Our study results suggest that multimorbidity indices differed in their ability to discriminate IC impairments. The comorbidity index derived from CIRS-G performed better than other multimorbidity indices included in this study. The comorbidity index has the potential as a simple proxy measure of indicating the need for interventions to optimise IC for older adults in community settings.

The ICOPE-WHO and the IVCF-20: a critical view of the Handbook for Multidimensional Geriatric Assessment in Primary Care

Rapid population aging is driving initiatives aimed at optimizing the health of older populations worldwide. In Brazil, the National Council of State Secretaries of Health (CONASS) recently published the Handbook for Multidimensional Geriatric Assessment in Primary Care, which proposes the combined, large-scale adoption of the World Health Organization (WHO) ICOPE screening tool and the Clinical-Functional Vulnerability Index-20 (IVCF-20) instrument to define care pathways for older people. Although there is a pressing need for initiatives of this nature, the proposed instruments have not yet been adequately validated in the Brazilian population, and their use for the purpose of establishing countrywide health guidelines appears hasty and risky. Therefore, we propose a broad, urgent debate among experts in the field with the aim of planning effective and safe public health policies for the Brazilian older population.

FC37: Prevalence of depressive symptoms and its association with probable sarcopenia, disability, frailty and comorbidities among older adults.

Objective:Depression is the most frequent cause of emotional distress in old age and can reduce the quality of life of the elderly. Sarcopenia is a syndrome characterized by the loss of skeletal muscle associated with reduced physical strength/performance. In recent years, some studies have shown correlations between sarcopenia and depression. The aim of the present study is to evaluate the association between depressive symptoms, sarcopenia, functional dependence and comorbidity in the geriatric patient at the first geriatric outpatient evaluation ever performed.Materials and Methods:older adults (&gt;=65 years of age) at their first access to the geriatric outpatient clinic of Modena County (Italy) between October 2020 and June 2021 were enrolled in this cross-sectional study. All participants were evaluated validated scales in order to perform a multidimensional geriatric assessment. The symptomatologic diagnosis of depression was performed through the GDS 4-item (cut-off &gt;=2). Frailty was evaluated through the Clinical Frailty Scale (cut-off &gt;=5). The probability of sarcopenia was evaluated through the SARC-F (cutoff &gt;=4). Functional dependence was assessed through the ADL scale and deemed as severe (ADL 0-2), moderate (ADL 3-5), absent (ADL 6). Comorbidity burden was assessed through CIRS.Results:229 patients (mean age 82.4±7.9 years, 67.6% female) were evaluated. Clinically significant depressive symptoms were found in 173 (75.5%) patients. Probable sarcopenia was reported in 118 (51.5%) patients while 100 (43.7%) and 64 (27.9%) patients were moderately or severely dependent, respectively. At multivariate logistic regression, probable sarcopenia (aOR 2.48, 95%CI 1.09-6.40), moderate functional dependence (aOR 2.62, 95%CI 1.17-5.87) but not severe (aOR 2.72, 95%CI 0.79-9.33) were associated with the presence of depressive symptoms. Conversely, frailty (aOR 0.97, 95%CI 0.39-2.40) was not associated with presence of depressive symptoms, while CIRS (aOR 0.79, 95%CI 0.66-0.96) was found to be protective.Discussion:the study showed that a clinically relevant depressive symptomatology is prevalent among older adults and it is associated with higher probability of sarcopenia and moderate, but not severe, functional dependence. On the contrary, there was no association between depressive symptoms and frailty.Conclusion:The prevalence of depressive symptoms is high among geriatric outpatient and can both be conditioned by and have an impact on the presence of sarcopenia and functional dependence.

Metabolomics and frailty: a "from bench to bedside" approach to atrial fibrillation in older patients

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia diagnosed at an advanced age. The most important complications of AF are stroke, heart failure and dementia. The pathophysiology of the arrhythmia is complex and multifaceted and several aspects are still not completely understood. Purpose Our project aimed at exploring the molecular characteristics of AF in older patients using an untargeted metabolomics approach, an analytical technique that provides an insight of the global metabolic profile at an individual level. As secondary endpoints, we evaluated the association between metabolomics and acylcarnitines, which are mediators of myocyte electrical instability, and difference in metabolomics profile between healthy controls (C) and AF patients (AF-P). Method We evaluated 50 consecutive older AF-P with persistent AF, waiting to be treated with elective electrical cardioversion of the arrhythmia, and 22 healthy controls (C). In all patients, the cardiological evaluation was integrated with tools of the Geriatric Multidimensional Assessment (GMA) to describe neurocognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (15-item Geriatric Depression Scale, GDS), and physical performance (Short Physical Performance Battery, SPPB). Interleukin-6 (IL-6), a marker of low-grade inflammation, was measured with ELISA assays. Metabolomics analysis and acylcarnitine measurements were carried out using gas chromatography coupled with mass spectrometry (GC-MS). Results AF-P and C did not differ by age (76 ± 6 vs. 70 ± 14 years, p = 0.055); patients had a lower proportion of women (AF-P: 32% vs. C: 64%, p = 0.012). Cluster analysis applied to metabolomic data in all population identified two subset of subjects, characterized by a different body mass index (BMI; 23.57 vs. 32.53 Kg/m², p = 0.046). When studying only the AF-P group, the simultaneous presence of a higher CHA2DS2-VASc score (4.17 ± 1.32 vs. 2.88 ± 1.83, p = 0.007), a lower physical function (SPPB; 8.97± 2.22 vs. 10.75 ± 1.13, p = 0.009), and higher IL-6 levels (4.42 vs. 2.39 pg/mL, p = 0.002) described the cluster with a worse clinical phenotype and a specific metabolomics pattern. Furthermore, an association between IL-6 and medium- long-chain acylcarnitines emerged (acylcarnitine 12:1, β = 31.7 ± 9.4, R = 0.446, p = 0.001). Conclusions Present analysis demonstrated that a specific metabolomics profile was characteristic of older AF patients with a frail phenotype, identified by higher CHA2DS2-VASc score and IL-6 concentration, and lower physical performance. Future studies are needed to reveal the single molecular pathways responsible of these behaviour, potentially useful to guide a targeted therapy. Last, inflammation per se could contribute to electrical instability in AF, while body mass index, a surrogate measure of undernutrition, could identify different metabolic pathways in controls and in patients with the arrhythmia.Metabolomics by clinical phenotypes

Prognostic Value of a New Tool (the 3D/3D+) for Predicting 30-Day Mortality in Emergency Department Patients Aged 75 Years and Older.

The 3D/3D+ multidimensional geriatric assessment tool provides an optimal model of emergency care for patients aged 75 and over who attend the Emergency Department (ED). The baseline, or static, component (3D) stratifies the degree of frailty prior to the acute illness, while the current, or dynamic, component (3D+) assesses the multidimensional impact caused by the acute illness and helps to guide the choice of care facility for patients upon their discharge from the ED. The objective of this study was to evaluate the prognostic value of the 3D/3D+ to predict short- and long-term adverse outcomes in ED patients aged 75 years and older. Multivariable logistic regression models were used to identify the predictors of mortality 30 days after 3D/3D+ assessment. Two hundred and seventy-eight patients (59.7% women) with a median age of 86 years (interquartile range: 83-90) were analyzed. According to the baseline component (3D), 83.1% (95% CI: 78.2-87.3) presented some degree of frailty. The current component (3D+) presented alterations in 60.1% (95% CI: 54.1-65.9). The choice of care facility at ED discharge indicated by the 3D/3D+ was considered appropriate in 96.4% (95% CI: 93.0-98.0). Thirty-day all-cause mortality was 19.4%. Delirium and functional decline were the dimensions on the 3D/3D+ that were independently associated with 30-day mortality. These two dimensions had an area under receiver operating characteristic of 0.80 (95% CI: 0.73-0.86) for predicting 30-day mortality. The 3D/3D+ tool enhances the provision of comprehensive care by ED professionals, guides them in the choice of patients' discharge destination, and has a prognostic validity that serves to establish future therapeutic objectives.

Multiparametric Evaluation of Geriatric Patients Admitted to Intermediate Care: Impact on Geriatric Rehabilitation.

Optimizing the functional status of patients of any age is a major global public health goal. Rehabilitation is a process in which a person with disabilities is accompanied to achieve the best possible physical, functional, social, intellectual, and relational outcomes. The Intermediate Care Unit within the O.U. of Geriatrics and Gerontology of the San Martino Hospital in Genoa is focused on the treatment and motor reactivation of patients with geriatric pathologies. The objective of this study was to identify which factor, among the characteristics related to the patient and those identified by the geriatric evaluation, had the greatest impact on rehabilitation outcomes. Our findings revealed significant correlations between the Barthel Index delta, the 4AT Screening Test, and the number of drugs taken. This association highlights the potential benefits of medication management in enhancing the overall well-being and functional abilities of frail older adults, despite the literature suggesting that polypharmacotherapy is associated with a reduction in functional status and an increase in mortality. These findings underscore the significance of a multidimensional geriatric assessment. Refining and optimising these multidisciplinary approaches is the objective of a more effective geriatric rehabilitation strategy.

PROGNOSTIC IMPACT OF FRAILTY ON FUNCTIONAL AUTONOMY IN OLDER ADULTS WITH HYPERTENSION

Objective: To date, few studies have evaluated frailty in older adults with hypertension and the most appropriate tool to quantify frailty in this population has yet to be identified. The present study aimed to investigate the prognostic impact of frailty on decline of functional autonomy in a sample of hypertensive older adults. Design and method: We performed a longitudinal observational study including patients aged 75 or older evaluated at the Hypertension Clinic and Memory Clinic of the Division of Geriatric and Intensive Care Medicine, Careggi Hospital, Florence. Participants underwent a multidimensional geriatric assessment including frailty evaluation using three frailty scales (Fried Frailty Phenotype, Clinical Frailty Scale [CFS], Frailty Index) and two physical performance measures (gait speed and Short Physical Performance Battery [SPPB]). The primary outcome was reduction of autonomy in daily activities according to the Barthel Index (functional decline). The predictive performance of different frailty measures was evaluated based on ROC curve analysis, sensitivity, specificity and accuracy. Results: Among 99 hypertensive older adults (mean age 81, 59% women, median follow-up 13 months), functional decline occurred in 39% of patients. Participants with functional decline had a higher prevalence of cognitive impairment and frailty according to all the frailty scales used and a worse physical performance. Frailty Index and CFS showed the best predictive performance (AUC 0.715 and 0.708, respectively), followed by physical performance measures (AUC 0.691). All frailty measures showed good specificity (66-79%) and moderate sensitivity (54-70%). Gait speed showed the highest accuracy (71%) and achieved 57% sensitivity and 79% specificity, resulting in better predictive performance than the SPPB. Conclusions: The CFS and gait speed - easily applicable even in non-geriatric settings – may represent useful instrument to detect frailty and predict functional decline in hypertensive older adults.

Abstract CT085: A phase 2/3, multicenter trial of lenzilumab and azacitidine in chronic myelomonocytic leukemia: The PREACH-M trial

Abstract Background: Chronic myelomonocytic leukemia (CMML) is a rare, aggressive cancer for which no targeted therapy exists. Standard of care (SOC) includes azacitidine (A), with complete and partial response (CR and PR) rates ranging between 10-17%. The pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a central role in stimulating leukemic monocyte proliferation. Lenzilumab (LENZ) is a proprietary Humaneered® first-in-class monoclonal antibody with best-in-class specificity and affinity that neutralizes GM-CSF to prevent signaling through its receptor. The PREcision Approach to CHronic Myelomonocytic Leukemia (PREACH-M) trial assesses the efficacy of LENZ in CMML (ACTRN12621000223831p) to improve outcomes beyond those afforded by SOC. Methods: PREACH-M is a Phase 2/3 non-randomized, open-label precision medicine trial in 72 adults aged at least 18 years, newly diagnosed with WHO 2016 criteria for CMML; cytopenia (hemoglobin &amp;lt; 100 g/L, platelets &amp;lt; 100 × 109/L or absolute neutrophil count &amp;lt; 1.8 × 109/L): white blood cell count ≥ 13 × 109/L; as well as TET2 and/or RAS pathway mutations (NRAS, KRAS, CBL). Key exclusion criteria include prior treatment with investigational agents; radiotherapy within 28 days before treatment; treatment with G-CSF within 7 days of screening; GM-CSF within 28 days of screening; and uncontrolled medical conditions. Subjects exhibiting RAS pathway mutations, with or without TET2 mutations, receive 24 cycles (28 days) of A (SC; 75 mg/m2 for 7 days) and LENZ (IV; 552 mg; d1 &amp; d15 of cycle 1 and d1 only for all subsequent cycles); while those with non-RAS pathway mutations receive the same A regimen and sodium ascorbate (IV; 30 g for 7 days [15 g for 1st dose only, 30 g thereafter if no evidence of tumor lysis syndrome]; PO; 1.1g on all other days). Subjects who complete 24 cycles of treatment are followed every 6 months for 24 months for survival, disease status, and CMML-related therapy. The primary endpoint is the frequency of CR or PR at any time during the first 12 cycles according to Savona Criteria. Secondary endpoints include overall survival and progression-free survival at 2 years; proportion of subjects with clinical benefit at any point during the 24 cycles; impact on physical and functional capacity; social well-being according to Multidimensional Geriatric Assessment and quality of life; as well as hematological and non-hematologic safety. Results: As of December 31, 2022, eight subjects were treated with A and LENZ (5 females, mean age of 67 years; 3 males, mean age of 69 years); among them 6 were evaluable based on at least 3 months of follow-up. CR or objective responses were observed in all evaluable patients including 2 with high risk based on molecular profiling. 10 grade 3/4 Serious Adverse Events were observed of which 2 were assessed by the investigator as possibly related to LENZ. Conclusion: The ongoing PREACH-M trial evaluates GM-CSF neutralization with LENZ in addition to SOC, in the treatment of CMML with RAS pathway mutations. Citation Format: Devendra Hiwase, David Ross, Steven Lane, Agnes Yong, Kirsty Sharplin, David Yeung, Lisa Butler, Dale Chappell, Cameron Durrant, Timothy Hughes, Daniel Thomas. A phase 2/3, multicenter trial of lenzilumab and azacitidine in chronic myelomonocytic leukemia: The PREACH-M trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT085.

Fast systematic geriatric assessment in acute heart failure patients admitted in Cardiology

BackgroundHeart failure prevalence is increasing in elder adults. These patients usually present geriatric syndromes, especially frailty. The effect of frailty on heart failure is under discussion but there are few data about the clinical characterization of frail patients who are admitted for acute heart failure decompensation. ObjectiveThe purpose of this study was to study the differences in clinical baseline variables and geriatric scales between frail and non-frail patients admitted to the Cardiology unit via the Emergency Department for acute heart failure. MethodsWe enrolled all patients with acute heart failure who were admitted to the Cardiology unit from the Emergency Department of our hospital from July 2020 through May 2021. A multidimensional and comprehensive geriatric assessment was performed at the moment of admission. We studied differences in baseline variables and geriatric scales according to the frailty status determined by the FRAIL scale. ResultsA total of 202 patients were included. In the whole population, 68 (33.7%) patients presented frailty defined by a FRAIL score ≥ 3. The frail patients were older (80±9 vs. 69±12 years; p<0.001), and had a worse quality of life (58.31±12.18 vs.39.26±13.71 points; p<0.001) according to the Minnesota scale, presented high comorbidity (47 (69.1%) vs. 67 (50.4%) patients; p = 0.011) defined as ≥3 points according to the Charlson scale and were more dependent (40 (58.8%) vs. 25 (18.8%) patients; p<0.001) according to the Barthel scale. The frail patients presented higher MAGGIC risk scores (24.09±4.99 vs. 18.89±6.26; p<0.001). Despite this adverse profile, the treatments prescribed during the admission and at the hospital discharge were similar. ConclusionsThe prevalence of geriatric syndromes, especially frailty, is very high in patients admitted for acute heart failure. Frail patients with acute heart failure had an adverse clinical profile with more prevalence of concomitant geriatric syndromes. Therefore, we consider that a geriatric assessment should be performed during the admission of acute heart failure patients to improve care and attention.

Avaliação multidimensional de pessoas idosas na Atenção Primária à Saúde: uma revisão de escopo

Abstract Objective to map the publications on multidimensional geriatric assessment in the primary care setting. Method A scoping review using the Joanna Briggs Institute methodology was carried out on the databases Web of Science, Scopus, Medical Literature Analysis and Retrieval System Online (MEDLINE) and Literatura Latino Americana e do Caribe em Ciencias da Saude (LILACS). The studies addressed the population of older people aged ≥60 years, the concept of multidimensional assessment and the primary care setting. Results a total sample of 19 publications was included for qualitative analysis. The studies selected were of different designs (predominantly cross-sectional) and most were in English. The evaluation comprised three dimensions; instruments developed applicable to primary care; two types of information technologies used to support the evaluation; and the relevant findings about the practice. Conclusion this review identified tools that were based on several existing instruments. Strategies should be tailored for assessing older individuals in a quick feasible manner. Specific domains were commonly present in the instruments, considered important for providing a comprehensive assessment tailored for the older population.

Multidimensional geriatric assessment in primary care: a scoping review

Resumo Objetivo mapear as publicações referentes à avaliação multidimensional de pessoas idosas no contexto da Atenção Primária à Saúde. Método Trata-se de uma revisão de escopo desenvolvida utilizando a metodologia Resultados foi incluída uma amostra total de 19 evidências para análise qualitativa, de variados delineamentos, com predominância do tipo transversal e em sua maioria na língua inglesa. Verificaram-se três dimensões que compõem a avaliação; instrumentos desenvolvidos aplicáveis à Atenção Primária; dois tipos de tecnologias da informação utilizadas para instrumentalizar a avaliação e achados relevantes sobre a prática. Conclusão esta revisão encontrou propostas de ferramentas construídas a partir de diversos instrumentos existentes. Devem ser criadas estratégias para atender aos idosos de forma rápida e factível. Foram verificados domínios prevalentes presentes nos instrumentos, constituindo-se como importantes quando se pensa em avaliar amplamente e de forma específica a população idosa.

Salivary gland cancers in elderly patients: challenges and therapeutic strategies.

Salivary gland carcinomas (SGCs) are the most heterogeneous subgroup of head and neck malignant tumors, accounting for more than 20 subtypes. The median age of SGC diagnosis is expected to rise in the following decades, leading to crucial clinical challenges in geriatric oncology. Elderly patients, in comparison with patients aged below 65 years, are generally considered less amenable to receiving state-of-the-art curative treatments for localized disease, such as surgery and radiation/particle therapy. In the advanced setting, chemotherapy regimens are often dampened by the consideration of cardiovascular and renal comorbidities. Nevertheless, the elderly population encompasses a broad spectrum of functionalities. In the last decades, some screening tools (e.g. the G8 questionnaire) have been developed to identify those subjects who should receive a multidimensional geriatric assessment, to answer the question about the feasibility of complex treatments. In the present article, we discuss the most frequent SGC histologies diagnosed in the elderly population and the relative 5-years survival outcomes based on the most recent data from the Surveillance, Epidemiology, and End Results (SEER) Program. Moreover, we review the therapeutic strategies currently available for locoregionally advanced and metastatic disease, taking into account the recent advances in precision oncology. The synergy between the Multidisciplinary Tumor Board and the Geriatrician aims to shape the most appropriate treatment pathway for each elderly patient, focusing on global functionality instead of the sole chronological age.

Allogeneic Hematopoietic Stem Cell Transplantation for Myelofibrosis: Role of Disease Status and Chimerism on Long-Term Outcomes

Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative option for Myelofibrosis (MF), a myeloproliferative neoplasm characterized by severely reduced survival. Despite a recognized superiority of transplant compared to medical options in higher risk MF, short-term complications substantially limit its use. Also, relapse can occur in a significant proportion of patients after allo-HCT. In this regard, controversial results have been reported on the predictive role of mixed chimerism. While CD33+ mixed chimerism was reported to correlate with worse OS due to higher risk of both relapse and non-relapse mortality (NRM), incomplete CD3+ chimerism was associated to an improved relapse-free survival. However, CD33 and CD3 antigens may not represent optimal markers for MF, since their expression, in contrast to CD34 antigen, has never been extensively described in MF. Herein we present a single Center experience on MF allo-HCT patients periodically monitored with CD34+, CD34- and mononuclear cells (MNC) donor chimerism with the aim to evaluate predictive factors for transplant outcome. Patients and methods. Overall, 31 MF patients were transplanted at the Unit of Bone Marrow Transplant of ASST Spedali Civili of Brescia from May 2014 to June 2022. Patients’ characteristics at time of transplant are detailed in table 1. Regarding transplant features, 15 patients received a myeloablative conditioning and 20 double-alkylators regimen (TBF in 19 and BuCy in 1 case). Donor was sibling, unrelated or haploidentical in 22.6%, 51.6% and 25.8% of cases. HCT-CI was high in 45.2%, FIL score unfit in 9.7% and KPS was 80 or less in 6.5% of cases, respectively. After transplant, the large majority of surviving patients underwent 1, 3, 6, 9, 12, 18 and 24-month donor chimerism, by using single tandem repeats (STR) PCR on patients’ bone marrow samples. Kaplan Meier was employed for computing OS. The Fine and Gray method was used for NRM and incidence of relapse (CIR). Three- and 6-month landmark analysis was utilized in order to evaluate the effect of mixed chimerism on outcomes. Univariate and multivariate analyses for OS were carried out using the Cox regression model. Logistic regression was employed for identifying factors associated with full donor chimerism. Results. After a median follow-up of 2.33 years (95%CI 1.02-3.20), 15 patients had died (6 relapse, 3 acute GVHD, 3 infections, 3 other causes) for a 5y CIR, NRM and OS of 21.7% and 30.5% and 48.6%. In Univariate analysis, high risk DIPSS (HR 3.91, 95%CI 1.40-10.95, p=0.009), FIL unfitness (HR 7.00, 95%CI 1.71-28.73, p=0.007), unfavorable cytogenetics (HR 4.88, 95%CI 4.88-1.36-17.49, p=0.015), accelerated phase disease (HR 3.84, 95%CI 1.32-11.17, p=0.013) and spleen palpable >15 cm below LCM (HR 4.50, 95%CI 1.49-13.53, p=0.008) were associated to reduced survival. In Multivariable analysis, accelerated phase disease (HR 8.03, 95%CI 1.68-38.52, p=0.009), splenomegaly (HR 15.64, 95%CI 3.12-78.47, p<0.001) and FIL unfitness (HR 33.43, 95%CI 3.97-281.40, p=0.001) maintained prognostic information. Importantly, high risk mutations did not prove any ability to predict survival after transplant (HR 1.60, 95%CI 0.51-4.98, p=0.420). Figure 1 illustrates the evolution of chimerism over time. Interestingly, 3 and 6-month MNC, CD34+ and CD34- mixed donor chimerism (<97.5%) was associated with significantly reduced survival (3-month landmark OS: 92.9% vs 20.0% [p=0.001], 100% vs 33.3% [p=0.003] and 100% vs 0% [p<0.001] at 1y; and 6-month landmark OS: 100% vs 0% [p<0.001], NA [only one patient with <97.5% donor chimerism], and 100% vs 0% [p=0.002] at 1 year, respectively), caused by increased CIR (data not shown). Double alkylator (HR 14.70, 95%CI 1.16-185.00, p=0.038) was the only parameter predicting an higher probability of reaching full donor chimerism after allo-HCT. Conclusions. Our study confirms the efficacy and safety of early transplant in MF. Patients submitted for transplant with massive splenomegaly or advanced stage disease appear to have a poor outcome. In addition, multidimensional geriatric assessment may represent an effective method to select MF allo-HCT candidates. The early achievement of full donor chimerism, as evaluated on MNC and CD34 lineages can predict a reduced risk for relapse and long-term survival. In this regard, use of double alkylating conditioning regimen could be relevant. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Advances in Transversal Topics Applicable to the Care of Bladder Cancer Patients in the Real-World Setting.

Simple SummaryThere are a number of scientific questions that are novel or controversial, which are clinically relevant in the real-world setting for patients diagnosed with bladder cancer, independently of the stage of disease or the histological type and grade of the tumors. These transversal topics have been discussed by a panel of expert specialists who participated in the Genitourinary Alliance Project, aimed to develop actions focused on the integration of relevant information into clinical practice. Advances in radiological imaging techniques have the potential of improving accuracy of staging methods, resulting in a more personalized planning and therapeutic option. The use of liquid biopsy will undoubtedly contribute to an increase in the efficiency of the evaluation of the clinical response and outcome of the disease. It is important to consider specific conditions of elderly people with bladder cancer, as well as the implementation of appropriate measures to enhance safe drug administration.Recommendations regarding transversal topics applicable to bladder cancer patients independent of tumor grade and stage were established by members of the Spanish Oncology Genitourinary Multidisciplinary Working Group (SOGUG). Liquid biopsy in urine and blood samples is useful in the surveillance of non-muscle-invasive and muscle-invasive bladder cancer, respectively. Multiparametric MRI is an accurate, faster and non-invasive staging method overcoming the understaging risk of other procedures. The combination of FDG-PET/MRI could improve diagnostic reliability, but definite criteria for imaging interpretation are still unclear. Hospital oncology pharmacists as members of tumor committees improve the safety of drug use. Additionally, safety recommendations during BCG preparation should be strictly followed. The initial evaluation of patients with bladder cancer should include a multidimensional geriatric assessment. Orthotopic neobladder reconstruction should be offered to motivated patients with full information of self-care requirements. Bladder-sparing protocols, including chemoradiation therapy and immune checkpoints inhibitors (ICIs), should be implemented in centers with well-coordinated multidisciplinary teams and offered to selected patients. The optimal strategy of treatment with ICIs should be defined from the initial diagnostic phase with indications based on scientific evidence. Centralized protocols combined with the experience of professional groups are needed for the integral care of bladder cancer patients.

Functional decline, long term symptoms and course of frailty at 3-months follow-up in COVID-19 older survivors, a prospective observational cohort study

BackgroundAging is one of the most important prognostic factors increasing the risk of clinical severity and mortality of COVID-19 infection. However, among patients over 75 years, little is known about post-acute functional decline.ObjectiveThe aim of this study was to identify factors associated with functional decline 3 months after COVID-19 onset, to identify long term COVID-19 symptoms and transitions between frailty statesafter COVID-19 onset in older hospitalized patients.MethodsThis prospective observational study included COVID-19 patients consecutively hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital. Functional decline, frailty status and long term symptoms were assessed at 3 month follow up. Functional status was assessed using the Activities of Daily Living simplified scale (ADL). Frailty status was evaluated using Clinical Frailty Scale (CFS). We performed multivariable analyses to identify factors associated with functional decline.ResultsAmong the 318 patients hospitalized for COVID-19 infection, 198 were alive 3 months after discharge. At 3 months, functional decline occurred in 69 (36%) patients. In multivariable analysis, a significant association was found between functional decline and stroke (OR = 4,57, p = 0,003), history of depressive disorder (OR = 3,05, p = 0,016), complications (OR = 2,24, p = 0,039), length of stay (OR = 1,05, p = 0,025) and age (OR = 1,08, p = 0,028). At 3 months, 75 patients described long-term symptoms (49.0%). Of those with frailty (CFS scores ≥5) at 3-months follow-up, 30% were not frail at baseline. Increasing frailty defined by a worse CFS state between baseline and 3 months occurred in 41 patients (26.8%).ConclusionsThis study provides evidence that both the severity of the COVID-19 infection and preexisting medical conditions correlates with a functional decline at distance of the infection.This encourages practitioners to establish discharge personalized care plan based on a multidimensional geriatric assessment and in parallel on clinical severity evaluation.

More than a third of middle-aged adults (50–65) have understated executive dysfunction

Objectives Understated executive dysfunction (UED) is predictive of cognitive decline and death. We aimed to assess the prevalence of UED, assessed with the clock-drawing test (CDT) and the Frontal Assessment Battery (FAB) in middle-aged adults and to investigate associated characteristics. Methods Cross-sectional analysis of data on 516 community-dwellers aged 50-65, lacking cognitive complaints, who were included prospectively (2010-2017) after a multidimensional geriatric assessment at a “healthy ageing” outpatient clinic. Age- and educational-level-adjusted logistic models were used to assess factors associated with UED. Results The CDT and FAB were impaired in 27.7% and 14.7% of the participants (median age: 59.7 years). The prevalence [95% confidence interval (CI)] of UED was 36.2% [32.2-40.5%]. After adjustment for age and education, participants with UED were more likely to be obese (odds ratio [95%CI] = 1.89 [1.12-3.19], P = 0.02), and to have a metabolic syndrome (1.98 [1.06-3.72], P = 0.03). Conclusion More than one third of middle-aged adults without cognitive complaints have UED, which was linked to obesity and metabolic syndrome. Cognitive screening tests targeting executive functions might be useful for early detection of UED and the initiation of multidomain interventions improving cognitive performance.

The VES-13 and G-8 tools as predictors of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients: A single-center study.

Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity. In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ≥70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy-seven consecutive patients aged ≥70 diagnosed with non-metastatic hormone-responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES-13 score ≥3 or G-8 score ≤14) and fit (VES-13 score <3 or G-8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients. The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value. The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ≥70.

Timed Up and Go as a predictor of mortality in older Indian patients with cancer: An observational study

Background: Therapeutic decision-making in older patients with cancer is challenging, and there is a need for a clinical parameter that can guide these decisions. The Timed Up and Go (TUG) test is an easy-to-administer tool that measures physical performance and may help to identify vulnerable patients.Objectives: We aimed to study the association between the TUG and overall survival in older Indian patients with cancer. We also aimed to evaluate the factors that were associated with a poor TUG score, to define the optimal cut-off score for older patients with cancer, along with the sensitivity and specificity.Materials and Methods: This prospective observational study was conducted in the geriatric oncology clinic at the Tata Memorial Hospital, a tertiary care center in Mumbai, India, between June 2018 and January 2022. We included adults aged 60 years and above, who had a diagnosis of malignancy, and had undergone a multidimensional geriatric assessment. Patients without a TUG score and for whom survival information was not available were excluded. Using the Short Physical Performance Battery (SPPB) as the gold standard, Receiver Operating Characteristic (ROC) curves with Area Under the Curve (AUC) were used, and the cut-off score with optimum sensitivity and specificity was derived. Mean values between two and more groups were compared using t test and analysis of variance, respectively. Categorical variables were compared using Fisher's exact and Pearson's Chi-squared test. The Kaplan–Meier survival estimate, and the unadjusted and adjusted Cox proportional-hazards model were used for survival analysis.Results: We enrolled 851 patients in the study. The median age was 69 (IQR, 65 to 73) years; 544 patients (76%) were men. We found that the TUG in women (median TUG, 11 seconds; IQR, 9.5 - 13.7) was longer than in men (median TUG, 9.6 seconds; IQR, 8.2 -11.6); P < 0.01. The TUG score increased significantly with increasing age in both sexes. Presence of comorbidities impaired cognition, poor nutritional status, depression, and anxiety were significantly associated with higher TUG scores. TUG was a significant predictor of mortality on both the univariate (HR, 1.056; 95% CI, 1.037–1.075) and multivariate models (HR, 1.058; 95% CI, 1.039–1.078). The median survival of patients with TUG <12 seconds was 13.9 months (95% CI, 11.2 to 16.5), compared to 8.5 months (95% CI, 6.6 to 10.3) in those with a TUG ≥ 12 seconds (P = 0.002). The TUG cut-off score of 10 seconds had an AUC-ROC, sensitivity of 62.32% and specificity of 80.58%.Conclusion: TUG can be a reliable tool in a busy outpatient setting to identify vulnerable patients who require a detailed geriatric assessment. A TUG score of ≥ 10 seconds is a good predictor of impaired mobility. Further 0.78 interventional studies are required to identify the benefits of physical therapy in older patients with cancer.