Cumulative Illness Rating Scale Research Articles

From Emergency Department to clinic center: management of patients with Heart Failure with Reduced Ejection Fraction

Aims: primary outcomes - cardiovascular and all-cause mortality evaluation within 1 year in elderly patients enrolled with Angiotensin Receptor Inhibitor (ARNI) and/or Sodium Glucose Co-Transporter Type 2 Inhibitors (SGLT2-i) in an Internal Medicine Department; recurrent hospitalization assessment for acute Heart Failure with Reduced Ejection Fraction (HFrEF); length of hospitalization analysis compared to not-enrolled patients. Secondary endpoints - to identify any parameters predicting the length of hospitalization; safety assessment through the incidence of complications and treatment interruption. Materials and Methods: prospective observational real-life cohort study that analyzes the recruitment during hospitalization and follow-up 3-6-12 months after discharge. Several clinical parameters were recorded for each patient of any ethnicity, considering a diagnosis of acute HFrEF with NT-proBNP and chest x-ray. Results: the enrolled group (34 patients) showed a hospitalization period lower than the not-enrolled one. The rehospitalizations percentage was inferior to Randomized Clinical Trials (RCTs) for ARNI. Cardiovascular-cause mortality, symptomatic hypotension, and Urinary Tract Infections (UTI) were lower than RCTs data. Age, eGFR, NT-proBNP, Cumulative Illness Rating Scale (CIRS), and severe comorbidities, except for EF, predicted the lengthening of hospitalization. Hypoglycemia wasn’t recorded. Conclusions: ARNI/SGLT2-i are effective and safe in elderly patients. Comorbidities and bio-humoral features influence HFrEF and quality of life. The future aim is to confirm the results obtained so far.

Implications of the consciousness state on decannulation in patients with a prolonged Disorder of Consciousness

to prospectively investigate the evolution of the consciousness state and the cannula-weaning progression in patients with prolonged Disorders of Consciousness (pDoC). non-concurrent cohort study SETTING: rehabilitation unit of the Fondazione Don Gnocchi, Florence PARTICIPANTS: adult patients, with a pDoC following a sABI admitted between 06.2020 and 09.2022 INTERVENTIONS: not applicable MAIN OUTCOME MEASURES: consciousness state was assessed by repeated Coma Recovery Scale-Revised (CRS-R) administration at admission, and weekly afterwards. The dates of the first improvement of consciousness state and the achievement of decannulation were recorded. Decannulation followed an internal protocol of multi-professional rehabilitation. 144 patients were included: age: 69 years, 64 (44.4%) with hemorrhagic etiology, time post-onset: 40 days, CRS-R at admission: 9, median length of stay: 90 days. Seventy-three (50.7%) patients were decannulated. They showed a significantly higher CRS-R (p<0.001) and states of consciousness (p<0.001) at admission, at the first improvement of the consciousness state (p=0.003), and discharge (p<0.001), a lower severity in the Cumulative Illness Rating Scale at admission (p=0.01), and a lower rate of pulmonary infections with recurrence (p=0.021), compared to non-decannulated patients. Almost all decannulated patients (97.3%) improved their consciousness before decannulation. Consciousness states at decannulation were: Unresponsive wakefulness Syndrome: 0 (0%), Minimally conscious state (MCS) minus: 4 (5.5%), MCS plus: 7 (9.6%), Emergence from MCS: 62 (84.9%). Kaplan-Meier analysis showed a significant divergence between the curves with a higher probability of decannulation in patients who improved consciousness (p<0.001). This study showed that the presence of signs of consciousness, even subtle, is a necessary condition for decannulation, suggesting that consciousness may influence some of the components implied in the decannulation process.

Comorbidity and multimorbidity in patients with cirrhosis, hospitalised in an internal medicine ward: a monocentric, cross-sectional study

ObjectivesThere are no data regarding the prevalence of comorbidity (ie, additional conditions in reference to an index disease) and multimorbidity (ie, co-occurrence of multiple diseases in which no one holds...

Rate and Causes of 30-day Unplanned Readmission/Return Following Head and Neck Surgery at a Tertiary Care Center in Saudi Arabia

Abstract Background: Identifying and targeting common preventable causes of 30-day hospital readmissions could help improve survival rates and reduce the healthcare burden. Objective: To determine the rate and causes of unplanned hospital return/readmission to the Outpatient Department (OPD) or Emergency Department (ED) within 30 days after discharge following head and neck surgery (HNS) at a tertiary hospital in Western Saudi Arabia. Methods: This retrospective study included all adult patients (aged ≥18 years) who had undergone HNS at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between January 2015 and December 2022 and returned to the OPD or ED within 30 days of being discharged. Results: Of 1041 patients who had undergone HNS, 84 (8.1%) returned to the hospital within 30 days after discharge: 63 (6.1%) to the OPD and 21 (2.0%) to the ED. A total of 9 (0.9%) patients were readmitted as inpatients, most commonly for infections (33.3%) and neurological symptoms, including weakness and seizures (22.2%). For OPD visits, common causes were wound swelling (25.4%) and neurological symptoms (17.5%). For ED returns, frequent causes were neurological symptoms (23.8%) and surgical site bleeding (19.1%). Readmission was associated with intensive care unit (ICU) admission during the primary hospital stay (P = 0.003) and higher preoperative baseline health burdens when examined using the American Society of Anesthesiology score (P = 0.022), the Cumulative Illness Rating Scale (P = 0.007), and the Charlson Comorbidity Index (CCI) (P = 0.006). Conclusion: The rate of 30-day unplanned hospital return following head and neck surgery was 6.1% and 2.0% through the OPD and the ED, respectively; 0.9% were readmitted as inpatients. Common causes of return included wound swelling, infections, bleeding, and neurological symptoms.

White matter hyperintensity patterns: associations with comorbidities, amyloid, and cognition

BackgroundWhite matter hyperintensities (WMHs) are often measured globally, but spatial patterns of WMHs could underlie different risk factors and neuropathological and clinical correlates. We investigated the spatial heterogeneity of WMHs and their association with comorbidities, Alzheimer’s disease (AD) risk factors, and cognition.MethodsIn this cross-sectional study, we studied 171 cognitively unimpaired (CU; median age: 65 years, range: 50 to 89) and 51 mildly cognitively impaired (MCI; median age: 72, range: 53 to 89) individuals with available amyloid (18F-flutementamol) PET and FLAIR-weighted images. Comorbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Each participant’s white matter was segmented into 38 parcels, and WMH volume was calculated in each parcel. Correlated principal component analysis was applied to the parceled WMH data to determine patterns of WMH covariation. Adjusted and unadjusted linear regression models were used to investigate associations of component scores with comorbidities and AD-related factors. Using multiple linear regression, we tested whether WMH component scores predicted cognitive performance.ResultsPrincipal component analysis identified four WMH components that broadly describe FLAIR signal hyperintensities in posterior, periventricular, and deep white matter regions, as well as basal ganglia and thalamic structures. In CU individuals, hypertension was associated with all patterns except the periventricular component. MCI individuals showed more diverse associations. The posterior and deep components were associated with renal disorders, the periventricular component was associated with increased amyloid, and the subcortical gray matter structures was associated with sleep disorders, endocrine/metabolic disorders, and increased amyloid. In the combined sample (CU + MCI), the main effects of WMH components were not associated with cognition but predicted poorer episodic memory performance in the presence of increased amyloid. No interaction between hypertension and the number of comorbidities on component scores was observed.ConclusionOur study underscores the significance of understanding the regional distribution patterns of WMHs and the valuable insights that risk factors can offer regarding their underlying causes. Moreover, patterns of hyperintensities in periventricular regions and deep gray matter structures may have more pronounced cognitive implications, especially when amyloid pathology is also present.

The Relationships between Caregiver Burden, Physical Frailty, Race, Behavioral and Psychological Symptoms (BPSD), and Other Associated Variables: An Exploratory Study.

Background and Objectives: For persons with dementia, the relationships between caregiver burden, physical frailty, race, behavioral and psychological symptoms (BPSD), and other associated variables are poorly understood. Only one prior study examined the relationships among these variables but did not include race, which is an important social determinant of health outcomes in the United States. To examine these interactions, we conducted a cross-sectional exploratory study based on a model by Sugimoto and colleagues. Materials and Methods: The sample comprised 85 patient-caregiver dyads (58% White) seen in four centers in diverse regions of New York State. All patients met DSM5 criteria for a major neurocognitive disorder, had a Clinical Dementia Rating sum score of ≥3, and Mini-Mental State Examination (MMSE) score of 10 to 26. Other measures included the SHARE-Frailty Instrument(FI), the Neuropsychiatric Inventory (NPI) to assess BPSD, Zarit's Caregiver Burden Interview (CBI), Lawton's Activities of Daily Living (ADL) Scale, the MMSE, the Cumulative Illness Rating Scale for Geriatrics (CIRSG), age, and gender. Results: In our sample, 59% met the criteria for prefrail/subsyndromal or frail/syndromal (SSF) on the SHARE-FI. SSF had significant direct effects on the NPI and significant indirect effects on the CBI mediated through the NPI; the NPI had significant direct effects on the CBI. Race (White) had significant direct effects on the CBI (higher) and SSF (lower) but did not have significant indirect effects on the CBI. MMSE, ADL, and CIRSG were not significantly associated with the NPI or the CBI. Conclusions: Our analysis demonstrated that frailty, race, BPSD, and caregiver burden may directly or indirectly influence one another, and therefore should be considered essential elements of dementia assessment, care, and research. These results must be viewed as provisional and should be replicated longitudinally with larger samples.

Rate and Causes of Unplanned Hospital Returns within 60 Days following Head and Neck Surgery

Abstract Introduction Unplanned hospital returns are frequent and may be preventable. Objective To comprehend the reasons for unplanned hospital readmission and return to the Outpatient Department (OPD) and Emergency Department (ED) within 60 days after discharge following head and neck surgery (HNS) at a tertiary care center in Saudi Arabia. Methods In the present retrospective study, the medical records of all patients who underwent HNS for benign and malignant conditions between January 2015 and June 2022 were reviewed in terms of demographic data, comorbidities, and reasons for hospital return. Results Out of 1,030 cases, 119 (11.55%) returned to the hospital within 60 days after discharge, 19 of which (1.84%) were readmitted. In total, 90 (8.74%) patients returned to the OPD, and 29 (2.82%), to the ED. The common reasons for readmission included infections (26.32%) and neurological symptoms (21.05%). For OPD visits, the common causes were hematoma (20%) and neurological symptoms (14.44%). For ED returns, the frequent causes were neurological symptoms (20.69%) and equipment issues (17.24%). Compared with nonreadmitted patients, readmitted patients had a higher preoperative baseline health burden when examined using the American Society of Anesthesiologists (ASA) score (p = 0.004) and the Cumulative Illness Rating Scale (CIRS; p = 0.002). Conclusion The 60-day rates of unplanned hospital return to the OPD and ED were of 8.74% and 2.82% respectively, and 1.84% of the patients were readmitted. Hematoma, infections, and neurological symptoms were common causes. Addressing the common reasons may be beneficial to decrease postoperative hospital visits.

The effect of social frailty on mental health and quality of life in older people: a cross-sectional study.

This study aims to evaluate anxiety, depression, loneliness, death anxiety, and quality of life and investigate their relationship with social frailty in the geriatric population. Additionally, it aimed to identify social frailty predictors. The study included 136 participants admitted to the geriatric outpatient clinic. The 15-itemGeriatricDepressionScale(GDS-15), the Multidimensional Scale of Perceived Social Support (MSPSS), the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), the Templer Death Anxiety Scale (T-DAS), the Loneliness Scale for the Elderly (LSE), the Quality of Life Scale (CASP-19), the Generalized Anxiety Disorder-7 Test (GAD-7), the Tilburg Frailty Indicator (TFI), the FRAIL Scale, and the Clinical Frailty Scale (CFS) were performed. The TFI was used to collect data about social frailty. There were 61.8% females, and the median age (min-max) was 72.2 (65.3-90.3) years. The prevalence rate of social frailty was 26.7%. The rates of depression, loneliness, anxiety, death anxiety, the burden of chronic disease, and frailty were higher in the social frailty group. Furthermore, logistic regression analysis revealed a strong relationship between social frailty status and widowhood (odds ratio (OR) 6.86; 95% confidence interval (95% CI), 2.42-19.37;p < 0.001), moderate to severe anxiety symptoms (OR 4.37; 95% CI 1.08-17.68; p = 0.038), and a TFI-physical frailty score (OR 1.40; 95% CI 1.12-1.73;p = 0.002). In older adults, the social dimension of frailty is associated with quality of life and psychological state. Physical frailty and sociodemographic characteristics may affect the development of social frailty.

Association of Depression With the Progression of Multimorbidity in Older Adults: A Population-Based Cohort Study

The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (β = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (β = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.

Total laryngectomy and readmission: causes, rates and predictors

BackgroundTotal laryngectomy (TL) is a complex procedure, and patients undergoing TL are at high risk for readmission, which exposes them to hospital-acquired complications. Readmission rate is a metric for quality of care. We aimed to identify the rate, causes, and predictors of hospital readmission within 60 days after discharge following TL.MethodsThis is a 12-year retrospective study where we included all patients undergoing TL in a single tertiary care center between 2008 and 2022. Patient charts were reviewed for demographics, comorbidities, and causes for readmission.ResultsOf 83 patients who underwent TL, 12 (14.50%) were readmitted within 60 days. Common causes were surgical site infection (33.33%) and mucocutaneous fistula (25%). Significant predictors for readmission were tobacco use (P = 0.003), African ethnicity (P = 0.004), being unmarried (P < 0.001), lower preoperative serum albumin (P < 0.001), higher preoperative TSH (P = 0.03), higher preoperative neutrophil count (P = 0.035), higher American Society of Anesthesiology (ASA) score (P = 0.028), and higher Cumulative Illness Rating Scale (CIRS) score (P = 0.029).ConclusionOne in every seven patients were readmitted following TL. Frequent causes include wound infection and fistulas. Predictors include preoperative hypoalbuminemia, hypothyroidism, African ethnicity, being unmarried, tobacco use, and a higher baseline burden of comorbidities. Such factors can be targeted to reduce hospital readmission rates.

Using magnetic resonance imaging to measure head muscles: An innovative method to opportunistically determine muscle mass and detect sarcopenia.

Sarcopenia is associated with multiple adverse outcomes. Traditional methods to determine low muscle mass for the diagnosis of sarcopenia are mainly based on dual-energy X-ray absorptiometry (DXA), whole-body magnetic resonance imaging (MRI) and bioelectrical impedance analysis. These tests are not always available and are rather time consuming and expensive. However, many brain and head diseases require a head MRI. In this study, we aim to provide a more accessible way to detect sarcopenia by comparing the traditional method of DXA lean mass estimation versus the tongue and masseter muscle mass assessed in a standard brain MRI. The H70 study is a longitudinal study of older people living in Gothenburg, Sweden. In this cross-sectional analysis, from 1203 participants aged 70years at baseline, we included 495 with clinical data and MRI images available. We used the appendicular lean soft tissue index (ALSTI) in DXA images as our reference measure of lean mass. Images from the masseter and tongue were analysed and segmented using 3D Slicer. For the statistical analysis, the Spearman correlation coefficient was used, and concordance was estimated with the Kappa coefficient. The final sample consisted of 495 participants, of which 52.3% were females. We found a significant correlation coefficient between both tongue (0.26) and masseter (0.33) with ALSTI (P<0.001). The sarcopenia prevalence confirmed using the alternative muscle measure in MRI was calculated using the ALSTI (tongue=2.0%, masseter=2.2%, ALSTI=2.4%). Concordance between sarcopenia with masseter and tongue versus sarcopenia with ALSTI as reference has a Kappa of 0.989 (P<0.001) for masseter and a Kappa of 1 for the tongue muscle (P<0.001). Comorbidities evaluated with the Cumulative Illness Rating Scale were significantly associated with all the muscle measurements: ALSTI (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.07-1.26, P<0.001), masseter (OR 1.16, 95% CI 1.07-1.26, P<0.001) and tongue (OR 1.13, 95% CI 1.04-1.22, P=0.002); the higher the comorbidities, the higher the probability of having abnormal muscle mass. ALSTI was significantly correlated with tongue and masseter muscle mass. When performing the sarcopenia diagnostic algorithm, the prevalence of sarcopenia calculated with head muscles did not differ from sarcopenia calculated using DXA, and almost all participants were correctly classified using both methods.

Examining the relationships between cognitive function and physical and mental health: interim findings from HKMMSOP

AbstractBackgroundPopulation ageing is associated with an increase in the number of persons with dementia, which constitutes a significant public health issue. The Hong Kong Mental Morbidity Survey for Older People (HKMMSOP) was carried out to evaluate the local prevalence of dementia and the factors that modulated the disease development.MethodParticipants aged 60 or over, stratified with age groups, were recruited through random sampling of residential addresses in Hong Kong. They underwent an assessment of their cognitive function (Montreal Cognitive Assessment, MoCA; Clinical Dementia Rating, CDR), physical health (Cumulative Illness Rating Scale, CIRS) and mental health (Clinical Interview Schedule‐Revised, CIS‐R; Short Warwick‐Edinburgh Mental Wellbeing Scale, SWEMWBS). Associative factors of neurocognitive disorders were determined by multinomial regression, with neurocognitive disorders as dependent variables.ResultIn this interim analysis, 4369 participants of HKMMSOP were included. Their mean age was 69.6, and there was a slight female preponderance (56.3%). On average, they received 8.8 years of education, and their mean MoCA score was 23.8 (SD 4.9). Using CDR, 71.8% were evaluated as having normal cognition, 23.1% with a mild neurocognitive disorder (ND), and 5.2% with a major ND. Older or less educated participants had a higher risk of developing mild and major ND (p&lt;0.001). But the relationships between cognition and physical and mental health differed in the mild and major ND groups. Among those with mild ND, a higher CIRS total score (p&lt;0.001), a higher CIS‐R total score (p&lt;0.001) and a lower SWEMWBS score (p = 0.002) were significantly associated with CDR. However, only CIRS total score (p = 0.004) and SWEMWBS score (p&lt;0.001) remained significant in the major ND group.ConclusionPoorer physical and mental health and lower mental well‐being and life satisfaction were associated with an increased risk of mild ND. But as the disease progressed, lower mental well‐being and life satisfaction and poorer physical health remained significant factors. On the contrary, a higher level of mental symptoms, as exemplified by CIS‐R, was not significantly associated with major ND. It sheds some light on the factors that may modulate the course of the disease and appropriate preventive measures.

A clinical trial of cognitive and biological effects of citrus phytochemicals in subjective cognitive decline: baseline sociodemographic, clinical, and cognitive characteristics

AbstractBackgroundWe designed a clinical trial to evaluate cognitive and biological effects of a 36‐week treatment with citrus peel extract in older adults with subjective cognitive decline (SCD) (ClinicalTrials.gov identifier: NCT04744922). Here we present baseline sociodemographic, clinical, and cognitive characteristics of the enrolled subjects.MethodEighty subjects were enrolled between April 2021 and August 2022, and randomly assigned to receive either active treatment (400 mg citrus peel extract standardized in content of auraptene ‐ 0.1 mg ‐ and naringenin – 3 mg) or placebo in a 1:1 ratio for 36 weeks. Data about nutritional state and comorbidity, current therapy, health‐related behaviours, cognitive performance on verbal and non‐verbal memory, attention, executive and visuospatial functions were collected. Differences between groups (termed group A and B to avoid unblinding – the treatment allocation is unknown to the investigators) were compared using independent t‐test or Fisher’s exact test.ResultThe enrolled subjects have a mean age of 69.2±4.3 years, a high level of education (mean 13.7±3.5 years) and a higher prevalence of females (75%), with no significant differences between groups A and B. Nutritional state and comorbidity were similar (Body Mass Index: 25.1±4.8 vs 24.0±3.9, p = .27 and Cumulative Illness Rating Scale: 1.46±0.22 vs 1.51±0.24, p = .38, groups A and B, respectively). The most frequent concurrent therapies included cardiovascular system and alimentary tract and metabolism drugs, with no significant differences between A and B (55% vs 63%, p = .32; 61% vs 66%, p = .41, respectively). Health‐related behaviours were also similar between A and B (Mediterranean Diet Adherence Screener: 9.0±1.9 vs 8.8±1.8; Smoking: 13% vs 8%; Alcohol consumption: wine 81% vs 83%, coffee consumption 93% vs 88%, all p = &gt;.30). Cognitive scores were all within the normal range and similar between groups, except for the Wisconsin Card Sorting test total score, where group A performed marginally better than group B (27.9±21.6 vs 40.7±32.2, p = .049).ConclusionThe trial is expected to complete the longitudinal assessment in April 2023. The results of this trial will enable to evaluate the efficacy of citrus phytochemicals in SCD, informing the design of future nutritional interventions in people at risk of decline cognitive.

The Role of the Cumulative Illness Rating Scale (CIRS) in Estimating the Impact of Comorbidities on Chronic Obstructive Pulmonary Disease (COPD) Outcomes: A Pilot Study of the MACH (Multidimensional Approach for COPD and High Complexity) Study.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous systemic syndrome that often coexists with multiple comorbidities. In highly complex COPD patients, the role of the Cumulative Illness Rating Scale (CIRS) as a risk predictor of COPD exacerbation is not known. The objective of this study was determine the effectiveness of the CIRS score in detecting the association of comorbidities and disease severity with the risk of acute exacerbations in COPD patients. In total, 105 adults with COPD (mean age 72.1 ± 9.0 years) were included in this prospective study. All participants at baseline had at least two moderate exacerbations or one leading to hospitalization. The primary outcome was a composite of moderate or severe COPD exacerbation during the 12 months of follow-up. The CIRS indices (CIRS total score, Severity Index and Comorbidity Index) showed a positive correlation with modified Medical Research Council (mMRC), COPD assessment test (CAT) and a negative correlation with forced expiratory volume in the first second (FEV1), Forced Vital Capacity (FVC), and FEV1/FVC. The three CIRS indices were able to predict the 12-month rate of moderate or severe exacerbation (CIRS Total Score: Hazard Ratio (HR) = 1.12 (95% CI: 1.08-1.21); CIRS Severity Index: HR = 1.21 (95% CI: 1.12-1.31); CIRS Comorbidity Index = 1.58 (95% CI: 1.33-1.89)). Among patients with COPD, the comorbidity number and severity, as assessed by the CIRS score, influence the risk in moderate-to-severe exacerbations. The CIRS score also correlates with the severity of respiratory symptoms and lung function.

Zanubrutinib vs FCR in Fit Treatment-Naive Patients with Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison

Background: Fludarabine, cyclophosphamide, and rituximab (FCR) is the standard first-line therapy for fit (physically active, with no major health problems and normal renal function) treatment-naive patients with chronic lymphocytic leukemia (CLL) (Eichhorst et al. Ann Oncol. 2015). Due to the safety profile of FCR, including severe hematotoxicity, and severe infections, treatments with improved efficacy and safety are of interest (Hallek et al. Lancet. 2010; Fischer et al. Blood. 2016). Zanubrutinib, a highly specific and potent small-molecule inhibitor of Bruton tyrosine kinase, has been approved for treatment-naive patients with CLL. However, the comparative efficacy of zanubrutinib vs FCR in patients with CLL has not been investigated. Objective: The objective of this study was to determine the relative treatment effects of zanubrutinib vs FCR in fit treatment-naive patients with CLL. Methods: The CLL10 trial (NCT00769522; Eichhorst et al. Lancet Oncol. 2016) investigated FCR and bendamustine + rituximab (BR), while the SEQUOIA trial compared zanubrutinib to BR (NCT03336333; Tam et al. Lancet Oncol. 2022). Zanubrutinib and FCR were compared by means of an anchored matching-adjusted indirect comparison (MAIC) in which the BR arm of each trial served as a common comparator. Propensity score matching was conducted using patient-level data from SEQUOIA to adjust for differences between trial populations, per National Institute for Health and Care Excellence MAIC methods (Philippo et al. NICE DSU Technical Support Document 18. 2016). Progression-free survival (PFS), as assessed by the independent review committee, was then compared based on the matched patient populations. The selection of matching variables was based on literature review and consultation with clinical experts. As the indirect treatment comparison was anchored on the common comparator arm (BR), patient characteristics that are solely prognostic did not need to be incorporated. The core model included immunoglobulin heavy chain gene mutation, cytogenetic mutations (11q deletion), β2-microglobulin, Binet stage, and age. Geographic region, sex, creatinine clearance, Cumulative Illness Rating Scale (CIRS) score, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous infections were tested in sensitivity analyses. Results: PFS was favorable with zanubrutinib vs FCR, and statistically significant differences were observed in the base case model (hazard ratio [HR], 0.41; 95% CI, 0.20-0.81; p-value=0.01). Sensitivity analyses showed significantly improved PFS with zanubrutinib when adding geographic region (HR, 0.43; 95% CI, 0.21-0.90; p-value=0.03), sex (HR, 0.44; 95% CI, 0.22-0.89; p-value=0.02), ECOG PS (HR, 0.30; 95% CI, 0.14-0.64; p-value&amp;lt;0.01), and previous infections (HR, 0.45; 95% CI, 0.22-0.93; p-value=0.03) to the base case set of matching variables. A sensitivity analysis incorporating CIRS (HR, 0.45; 95% CI, 0.16-1.24; p-value=0.12) showed only numerically favorable PFS with zanubrutinib, owing in part to the low effective sample size (ESS) in the expanded model. Similar results were obtained when creatinine clearance was added to the base case matching set of variables (HR, 0.52; 95% CI, 0.24-1.13; p-value=0.10). Conditional on the number of matching variables, ESS ranged from 174.1 in the core model to 64.05 in the analysis that included the CIRS score. Conclusion:Our findings suggest that zanubrutinib offers clinically meaningful benefits in PFS over FCR in fit treatment-naive patients with CLL. MAICs rely on reporting of relevant patient characteristics in published studies. In the current study, ZAP-70 methylation and TP53 mutation, which were considered treatment effect modifiers, were not reported in CLL10 and were not accounted for in the propensity model.

Frailty Impact on Outcomes of Patients Undergoing Chimeric Antigen Receptor T-Cell (CAR T) Therapy at Princess Margaret Cancer Centre: A Prospective Pilot Study

Introduction Princess Margaret Cancer Centre is 1 of 3 adult centres in Ontario, Canada providing Chimeric Antigen Receptor T-Cell (CAR T) therapy as a standard of care treatment for adult patients with relapsed and refractory B-cell lymphomas. There is no upper age limit for treatment consideration, and frailty may be an important factor in assessing fitness for treatment. This study aims to determine if frailty assessments pre-CAR T can predict those at higher risk for acute toxicities, PFS, and OS, as well as evaluate changes in frailty over time. Methods We performed a cohort study of consecutive patients with lymphoma undergoing CAR T cell therapy at our institution, from April 2021 to date. Frailty was evaluated using the Clinical Frailty Scale (CFS), Grip Strength, Gait Speed, Mini-Cog, Edmonton Symptom Assessment System (ESAS) and Patient Health Questionnaire (PHQ-2 and PHQ-9) at 5 time points: baseline (clearance visit), and 1, 3, 6 and 12 months post-CAR T. At baseline, additional assessments were completed to further characterize frailty including the Vulnerable Elders Survey (VES-13), Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and Cumulative Illness Rating Scale (CIRS). We present data on patients enrolled to date. Results Fifty-two patients have had their data analyzed thus far. Mean age is 57.9 ± 12.7 years and 54% are male. 50% have de novo diffuse large B-cell lymphoma, 24% transformation from follicular lymphoma,14% HGBCL, 6% PMBCL and 6% FL. Most patients (83%) received axi-cel. Median follow-up is 3.80 months (IQR 0.56-24.7 mo). All 52 patients completed assessments at baseline, 44 completed 1 month, 25 completed 3 month, 12 completed 6 month and 11 completed 12 month assessments. Median scores (and IQR) for the HCT-CI, CIRS, VES-13 and CFS at baseline were 1.5 (0-5), 3.0 (0-13), 1.0 (0-7), and 3.0 (1-7) respectively. There were clinically significant changes observed in CFS over time ( p=&amp;lt;0.001), with mean scores of 3.3 at baseline, 3.7 at 1 month, 2.8 at 3 months and 2.1 at 12 months. There were no significant changes ( p=0.051; p=0.078) between timepoints for either of the physical assessments of grip strength or gait speed. Sixteen patients (31%) experienced immune effector cell neurotoxicity syndrome (ICANS) (4% Grade 4, 4% Grade 3, 8% Grade 2, 15% Grade 1) and forty-nine patients (94%) experienced cytokine release syndrome (CRS) (2% Grade 3, 65% Grade 2, 27% Grade 1), during the 30 days following cell re-infusion. Seven patients (13%) were admitted to the ICU, with a median in-hospital length of stay for all 52 patients of 12.5 days (IQR 7.0, 99.0). None of the variables tested (age, sex, bridging therapy, LDH, CRP and frailty assessments) were significantly associated with the development or grade of CRS or ICANS. There have been 21 progression events and 18 deaths (6 without progression); 9 pts remain alive post-progression (Figure 1). On univariable analysis of baseline data, ECOG performance status, LDH level, and the VES-13 score were predictive of PFS, while ECOG, LDH, CRP, VES-13 score, CFS and the time to walk 4m were predictive of OS. The HCT-CI and CIRS score were not significantly associated with outcomes. On multivariable analysis of PFS, baseline VES-13 score (HR 1.17, p=0.04) and LDH (HR 1.002, p=0.05) remained significant. Multivariable analysis for OS was not performed due to insufficient number of events. Analyses incorporating repeated measures were performed, and on univariable analysis, the CFS, 4m walk test (s), LDH, VES-13 were significantly associated with PFS and the same variables and CRP were associated with OS (Table 1). On multivariable repeated measurements analyses, only the CFS was still associated with PFS, and CFS and LDH with OS (Table 1). Conclusions Conducting serial frailty assessments in patients undergoing CAR T therapy is feasible. The only longitudinal measurement of frailty found to have clinically significant changes between timepoints was the CFS, suggesting an element of reversible functional impairment related to patients' lymphoma. Within the limits of our sample size, baseline measures of frailty were not predictive of CRS or ICANS; the relationship of CFS change over time with PFS and OS may be indicative of lymphoma response. Enrollment is ongoing and data on larger number of patients with longer term follow-up are needed.

A Multicenter Retrospective Study to Understand the Clinical Characteristics, Treatment Patterns, and Resource Utilization for Patients with Chronic Lymphocytic Leukemia: CREEK Study

Abstract Introduction: The ever-growing array of treatments available for chronic lymphocytic leukemia (CLL) led to a significant change in CLL management over the last few years. However, information about managing CLL is scattered across various regions, resulting in significant disparities in treatment approaches and patient outcomes between countries. The CREEK study aimed to describe the disease characteristics, treatment patterns, and overall survival (OS) among CLL-treated (CLL-Tx) patients and CLL treatment-naïve (CLL-N) patients in different regions. Methods: Data from 1009 patients were collected retrospectively from June 2016 to March 2023. This observational study included 886 CLL-Tx patients from 17 countries in the Middle East and Africa (MEA), Asia Pacific (AP), and Latin America (LA); and a pilot cohort of 123 CLL-N patients from the Gulf Cooperation Council (GCC) countries. Patients' demographics, disease characteristics, laboratory assessments, comorbidities, treatment patterns, treatment-related adverse events (AEs), OS, and medical resource utilization (MRU) data were recorded. Results: The average age for both cohorts was 63 years. Most patients were males, 66.7% in CLL-Tx and 69.9% in CLL-N. The mean duration from clinical manifestation until diagnosis was 21.37 months for CLL-Tx and 1.46 months for CLL-N patients (p&amp;lt;0.0001). For CLL-Tx, almost 62% of the patients in MEA, 59.3% in AP, and 68.8% in LA had an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, and similarly for CLL-N patients (56.1%). Total leucocytic count, lymphocytes, and platelets showed a significant difference (p&amp;lt;0.05) between CLL-Tx and CLL-N patients. As per the Cumulative Illness Rating Scale (CIRS), musculoskeletal (p&amp;lt;0.0008) and endocrine-metabolic (p&amp;lt;0.0001) comorbidities were more frequent in the CLL-Tx group. Regarding the CLL-Tx patients, 69.7%, 62.9%, and 41.1% had extremely severe hematological problems (CIRS score 4) in MEA, LA, and AP, respectively. At diagnosis, patients from the MEA region presented with the highest prevalence of advanced disease staging, with 44.8% and 35.3% based on Rai and Binet Staging Scores, respectively; moreover, CLL-Tx patients exhibited a more advanced staging compared to CLL-N based on the same scores (p &amp;lt;0.0001). FISH testing for disease prognosis was not performed in about 59% of the patients across all regions. The testing rates for cytogenetic abnormalities, IGHV mutation status, and TP53 aberrations were relatively low in all regions. The percentage of unmutated IGHV was considerably higher (p=0.0001) in CLL-Tx (15.6%) patients, with the highest percentage in LA (21.0%), compared to CLL-N (10.6%). Cytogenetic abnormalities did not show significant differences between CLL-Tx and CLL-N patients (p&amp;gt;0.05), while TP53 aberrations differ significantly (p&amp;lt;0.05) (Table 1). Most patients, 76.0%, 81.8%, and 69.4%, received chemo-immunotherapies as 1 st line therapy, while 18.3%, 17.1%, and 30.1% received targeted therapy in MEA, AP, and LA, respectively. The percentage of patients with AEs who received 1 st line chemo-immunotherapies was higher than those who received targeted therapy (25.6% vs. 7.3%). The mean OS was 153.89 months in the treated study population (Table 2). The mean number of inpatient hospitalizations was 1.9 times for chemo-immunotherapy and 0.8 times for targeted therapy. The mean lengths of stay of 14.9 and 13.9 days, respectively; mean emergency room visits were 0.5 and 0.7, and blood transfusions were received by 16.7% and 9.2% of patients, respectively. Conclusions: This study highlights the variable disease characteristics between CLL-Tx and CLL-N patients and provides insight into the regional variations in treatment patterns and OS for CLL-Tx patients. A considerable number of patients had advanced disease staging at diagnosis; however, the study showed relatively low genetic testing rates, indicating the need for adequate clinical watchfulness. Despite being in the era of approved targeted therapy, the utilization of chemo-immunotherapy continues to be higher than that of targeted therapy in the first line, probably due to the lower access to targeted therapies. Keywords: Chronic Lymphocytic Leukemia (CLL), Genetic Testing, Treatment Patterns, Targeted Therapy, Chemo-immunotherapy, Real World Data.

Comprehensive Geriatric Assessment in Diffuse Large B-Cell Lymphomas Patients Older Than 70 Years Old: Prospective Single-Center Experience

CONCLUSIONS Diffuse large B-cell lymphoma (DLBCL) is diagnosed at a median age of 65 years, and around 40% of the patients are older than 70 years. Because of frailty and comorbidities, standard chemoimmunotherapy delivery may be very challenging in this setting. Therefore, a more personalized approach based on comprehensive geriatric assessment (CGA) may be warranted, as already proposed by other international groups. We aim to evaluate the impact of the establishment of a CGA on therapeutic decisions and outcome in our older population of pts with DLBCL. From January 2018 to May 2023, some unselected (depending on the referring hematologist) patients ≥70 years old with DLBCL were prospectively evaluated by a geriatrician at Catalan Institute of Oncology. CGA included validated instruments to assess: comorbidity with Charlson Index and Cumulative Illness Rating Scale (CIRS); polypharmacy; functional status in terms of activities daily living (ADL) with Barthel scale and instrumental ADL with Lawton scale; geriatric syndromes; mood with Yeasauvage scale; cognition with Pfeiffer scale; and social status. According to global CGA, patients were classified in 3 frailty groups: type 1, fit for standard chemoimmunotherapy (S-CT); type 2, fit for reduced intensity chemoimmunotherapy (RI-CT); type 3, candidate to palliative treatment. Among 247 newly diagnosed DLBCL, 101 (41%) patients had ≥70 years, of which 38 underwent CGA. Among patients who underwent CGA, 14 (37%) were classified as type 1, 20 (53%) type 2 and 4 (10%) type 3. Type 1 patients were younger (median age 75, ≥80 yrs 29%), than type 2 (median age 79, ≥80 yrs 55%), and type 3 (median age 93, ≥80 yrs 100%). The characteristics of 63 pts ≥70 years who did not underwent CGA did not differ significantly from the population in the study, except they had lower extranodal involvement and a higher proportion of patients did not received treatment (Table 1). All the evaluated 38 patients received treatment (Figure 1), 34 with immunochemotherapy (Table 1), and 5 patients (4 of type 3 and 1 of type 2) were palliatively handled: 1 with radiotherapy and 4 with cyclophosphamide monotherapy with or without prednisone. During treatment, 2 patients (one of type 1 and one of type 2) were deescalated from RCHOP to RminiCHOP due to severe infectious complications, while 6 patients of type 2 were upgraded, as previously planned if treatment was well tolerated. The most common adverse event was infection in 36% of patients (in 21% grade 3/4). Twelve patients (4 of type 1 and 8 of type 2) experienced at least an infectious event. Two toxic fatal events (1 patient of type 2 of septic shock and 1 of type 1 of urinary tract infections in the contest of bladder fistula) were reported. There were treatment delays in 10 (29%) patients (5 of type 1 and 5 of type 2). Among 33 patients who received active treatment, 4 had not been evaluated yet, and 29 were evaluable for response: overall response rate (ORR) was 71% and the complete remission (CR) rate was 68% (71% with S-CT and 68% with RI-CT). With a median follow-up of 12 months (range, 1-133), the 1-year event-free survival (EFS) and overall survival (OS) of the study population were 57% (95% CI, 38-71) and 72% (95% CI, 52-84), respectively. Among patients without CGA, the 1-year EFS and OS were 57% (95% CI, 44-69) and 67% (95% CI, 53-78), respectively. According to CGA, the 1-year EFS of type 1 patients was 68% (95% CI 35-87), type 2 was 61% (95% CI, 34-79) and type 3 was 0%. The 1-year OS of type 1 patients was 66% (95% CI 32-86), type 2 was 82% (95% CI, 52-94) and type 3 was 50% (95% CI, 1-84) (Figure 1). In this homogeneous series of older patients with DLBCL, our results confirmed the importance of CGA. Within a multidisciplinary approach, we may accurately classify the fitness of patients and offer them the best therapeutic options without causing excessive toxicity, as proved by similar EFS estimates between type 1 and 2 subgroups. Further larger studies are needed to evaluate potential geriatric interventions aimed at further improving outcomes.

Simplified Geriatric Assessment-Albumin: The Modified Tool for Older Diffuse Large B-Cell Lymphoma in China

Introduction Geriatric assessment can aid in optimizing treatment strategies and supportive interventions for older adults with diffuse large B-cell lymphoma (DLBCL). Recently, Fondazione Italiana Linforni developed the simplified Geriatric Assessment (sGA) and Elderly Prognostic Index (EPI) to tailor treatment and predict the prognosis of DLBCL in older adults. Herein, we validated the prognostic value of sGA and EPI, and modified the sGA to make it more effective for older DLBCL patients in China. Methods A total of 257 patients with DLBCL aged ≥65 years from Beijing Hospital and Peking University Third Hospital were included in the study. The sGA, which was modified from original geriatric assessment (oGA), incorporates age, activities of daily living (ADL), instrumental ADL, and Cumulative Illness Rating Scale for Geriatrics (CIRS-G), identifying patients into fit, unfit, and frail group. EPI integrated sGA with the IPI score and hemoglobin, identifying patients into low-, intermediate-, and high-risk group. Early mortality was defined as any death occurring within three months from the date of diagnosis. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to assess survival rates and the sensitivity and specificity of the geriatric assessment tools, respectively, whereas the log-rank test was used for comparison. Univariate and multivariate Cox regression analyses were used to identify the independent biomarkers for the patients. Logistics regression analyses were used to analyze the correlation between the geriatric assessment tools and early mortality. Results In the study, both sGA and EPI were related to the progression-free survival (PFS; Figure 1A and 1B), overall survival (OS; Figure 1C and 1D), and early mortality of older patients with DLBCL in China (All p &amp;lt; 0.05). Although they had no ability to predict PFS ( p &amp;gt; 0.05; Figure 1E), ROC curves showed that sGA could predict OS ( p = 0.006; AUC: 0.602; 95%CI: 0.530-0.674; Figure 1F), and early mortality ( p = 0.002; AUC: 0.744; 95%CI: 0.634-0.853; Figure 1G) in older patients with DLBCL in China. As for EPI, it also could predict OS ( p = 0.027; AUC: 0.584; 95%CI: 0.512-0.656; Figure 1F) and early mortality ( p = 0.009; AUC: 0.703; 95%CI: 0.590-0.815; Figure 1G). To make the geriatric tools more effective for older patients with DLBCL in China, albumin, the independent prognostic biomarker for OS of the cohorts, was added into sGA to establish the modified tool sGA-A (Table 1). According to sGA-A, patients were stratified into fit (36.7%), unfit (30.9%), and frail (32.4%) group. However, 1 patient was excluded due to the deficiency of albumin. The sGA-A was associated with age ( p &amp;lt; 0.001), Ann Arbor stage ( p = 0.002), ECOG-PS ( p &amp;lt; 0.001), lactic dehydrogenase (LDH; p = 0.001), IPI score ( p &amp;lt; 0.001), B symptom ( p &amp;lt; 0.001), hemoglobin ( p &amp;lt; 0.001), and albumin ( p &amp;lt; 0.001). Besides, sGA-A was related to PFS ( p &amp;lt; 0.001; Figure 1H), OS (( p &amp;lt; 0.001; Figure 1I), and early mortality ( p = 0.010) of older patients with DLBCL in China. Furthermore, ROC curves showed that sGA-A not only could predict OS ( p &amp;lt; 0.001; ACU: 0.647; 95%CI: 0.577-0.717; Figure 1F), and early mortality (p = &amp;lt; 0.001; AUC: 0.769; 95%CI: 0.679-0.859; Figure 1G), but also could predict PFS ( p = 0.046; AUC:0.577; 95%CI: 0.502-0.652; Figure 1E). In predicting OS, sGA-A was superior to sGA ( p = 0.010), EPI ( p = 0.006). As for early mortality, sGA-A was superior to the EPI ( p = 0.033), but not sGA ( p = 0.520). Conclusions In the study, we validated that sGA and EPI could predict OS and early mortality of older patients with DLBCL in China. Based on sGA, we propose sGA-A, which combined sGA and albumin, as an effective tool for geriatric assessment in DLBCL. The sGA-A compensated for the deficits of the sGA and EPI in predicting PFS, and was superior to sGA and EPI in predicting OS and early mortality. However, further investigations on whether sGA-A could guide the treatment may assist clinicians in improve the prognosis of older patients with DLBCL.

First-Line Fixed-Duration Ibrutinib Plus Venetoclax (Ibr+Ven) Versus Chlorambucil Plus Obinutuzumab (Clb+O): 55-Month Follow-up from the Glow Study

Introduction : In the GLOW trial (NCT03462719), fixed-duration Ibr+Ven treatment has shown superiority to Clb+O in progression-free survival (PFS), better sustained undetectable minimal residual disease (uMRD) responses, and overall survival (OS) benefit in patients with previously untreated chronic lymphocytic leukemia (CLL) who are older and/or have comorbidities (CU Niemann, et al. Blood. 2022;140[suppl 1]:228-230). In this analysis, we report clinical outcomes, including PFS, OS, and MRD analysis, from the Ibr+Ven combination in GLOW with a median follow-up of 55 months, including subgroup analyses by IGHV and MRD. Methods : Patients aged ≥ 65 years or 18 to 64 years with a Cumulative Illness Rating Scale score &amp;gt; 6 or creatinine clearance &amp;lt; 70 mL/min were randomized 1:1 to Ibr+Ven (3 cycles of Ibr lead-in, followed by 12 cycles of Ibr+Ven; N = 106) or 6 cycles of Clb+O (N = 105). Each cycle was 28 days. Patients were excluded if they had del17p or known TP53 mutations at screening. End points included investigator-assessed PFS, uMRD rates, time to next treatment (TTNT), and OS. MRD was assessed sequentially over time in peripheral blood by next-generation sequencing for patients with partial response (PR) or better. Patients with &amp;lt; 1 CLL cell per 10,000 leukocytes (&amp;lt; 10 -4) were considered to have uMRD, whereas patients with ≥ 1 CLL cell per 10,000 leukocytes (≥ 10 -4) were considered to have detectable MRD (dMRD). All p values reported were nominal. Safety was not further assessed, as all patients were already past the treatment period in previous analyses. Results of updated analyses : With a median follow-up of 55 months, PFS remained superior for Ibr+Ven (hazard ratio [HR] 0.239 [95% confidence interval (CI), 0.159-0.359]; p &amp;lt; 0.0001); 54-month PFS rates were 65.8% for Ibr+Ven and 19.1% for Clb+O. In the Ibr+Ven arm, for patients with unmutated IGHV (uIGHV; n = 67) and mutated IGHV (mIGHV; n = 32), 54-month PFS rates were 58% and 90%, respectively. Also in the Ibr+Ven arm, PFS rates at 3 years post-treatment were 82% in patients who achieved uMRD at 3 months after end of treatment (EOT+3; n = 58) and 73% for patients with dMRD (n = 31). Among patients with uIGHV, PFS rates at 3 years post-treatment were 81% for those achieving uMRD at EOT+3 (n = 40) and 56% for those with dMRD (n = 16). In patients with mIGHV, PFS rates at 3 years post-treatment were ≥ 92% regardless of MRD status at EOT+3. Overall, at 38 months after end of treatment (EOT+38), 32.1% of patients had uMRD in the Ibr+Ven arm. Of the patients who achieved uMRD at EOT+3 (n = 58), 53.4% sustained uMRD status at EOT+38 in the Ibr+Ven arm. In addition, TTNT was prolonged for patients receiving Ibr+Ven versus Clb+O. The risk of needing second-line therapy was significantly reduced by 83% with first-line Ibr+Ven versus Clb+O (HR 0.174 [95% CI, 0.088-0.342]; p &amp;lt; 0.0001), and by 85% among patients with uIGHV (HR 0.146 [95% CI, 0.069-0.310]) compared with a 29% risk reduction in those with mIGHV (HR 0.708 [95% CI, 0.118-4.256]). In the Ibr+Ven arm, 4 patients received single-agent ibrutinib as subsequent therapy as part of the study; while 1 patient had not yet had a disease assessment, the best response for the other 3 patients were complete response (n = 1) and PR (n = 2). Finally, Ibr+Ven continues to demonstrate improved OS versus Clb+O, reducing the risk of death by 58% (HR 0.421 [95% CI, 0.237-0.747]; p = 0.0023). Estimated 54-month OS rates were 84.5% for the Ibr+Ven arm and 63.1% for the Clb+O arm. Conclusion : With prolonged follow-up of 55 months in the GLOW study, all-oral, once-daily, fixed-duration Ibr+Ven continues to show superior PFS versus Clb+O. Among patients treated with Ibr+Ven, benefit in PFS was particularly observed in patients with uIGHV who achieved uMRD at EOT+3 and in patients with mIGHV regardless of MRD status at EOT+3. Moreover, Ibr+Ven fixed-duration combination treatment continues to demonstrate an OS advantage versus chemoimmunotherapy in patients with previously untreated CLL.