Group Of Older Patients Research Articles

Association of phase angle with hospital-acquired functional decline in older patients undergoing cardiovascular surgery

ObjectiveThe aim of this study was to examine whether preoperative phase angle (PhA) measured by bioelectrical impedance analysis was associated with a hospital-acquired functional decline in older patients undergoing cardiovascular surgery. MethodsThis was an observational study of prospectively collected data of 114 patients (>65 y of age) with cardiovascular disease who underwent elective cardiovascular surgery between September 2019 and August 2020. Patients were classified into tertiles based on PhA levels. Factors associated with the occurrence of hospital-acquired functional decline (postoperative recovery to preoperative physical function was not possible) were analyzed using univariate and multivariate analyses. ResultsPatients in the low PhA group were significantly older than those in the middle and high PhA groups; were predominantly women; had higher New York Heart Association cardiovascular and EuroSCORE severity scores; and had significantly lower levels of body mass index, Geriatric Nutritional Risk Index, hemoglobin, and albumin. There was a significant correlation between PhA and nutrition and physical function. The incidence of hospital-acquired functional decline occurred in 26.3% of all patients, with a significantly higher incidence in patients in the low PhA group. Multivariate analysis showed that PhA was extracted as a factor for the hospital-acquired functional decline in all the models. ConclusionsPhA was associated with hospital-acquired functional decline in older patients undergoing cardiovascular surgery. PhA is likely to be a comprehensive indicator of physical health that indicates nutritional status, physical function, and geriatric syndrome (frailty/sarcopenia), and is an important predictor of hospital-acquired functional decline in this group of older patients.

Chemosensitive Disease Better Predicts Outcome Than Age Following Autologous Heamatopoietic Stem Cell Transplantation in Elderly Patients with Multiple Myeloma

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is considered the standard of care as first-line therapy for eligible multiple myeloma patients(Barlogie et al. 1987; McElwain & Powles 1983). Median age at diagnosis of multiple myeloma is 69 years old (SEER 18 2010-2014). Data from the CIBMTR revealed that the number of transplants done per year and the age of recipients are still rising(D'Souza & Zhu 2016). With an expected myeloma prevalence rising by 57% from 2010 to 2030(Smith et al. 2009), the number of older patients considered for AHSCT will increase significantly. Best treatment options for those older patients must therefore be addressed. The assessment of hematopoietic cell transplant comorbidity index score (HCT-CI) (Sorror et al. 2005; Sorror et al. 2009) can be helpful in the selection of candidates for AHSCT. The goal of this study was to identify factors impacting the safety and efficacy of AHCT in older multiple myeloma patients in order to better select those who will benefit from such an intervention.This single center, retrospective study examines outcomes of AHSCT in elderly patients (≥60 years old) with multiple myeloma compared to younger patients (<60 years old). Between January 1, 2011, and September 1, 2015, 93 patients met the inclusion criteria and were included in the study. Patients signed an informed consent and the ethics committee of our institution approved the study. Toxicity was analyzed according to age and HCT-CI. Progression-free-survival (PFS) and overall survival (OS) were analyzed according to age at the time of transplantation, HCT-CI, Revised International Staging System (R-ISS) and disease status at the time of transplant.From the 93 patients included in the study, 49(53%) were included in the younger patient group with a median age at transplant of 54 years-old (range 34 to 59). Forty-four (44) patients were included in the older patient group with a median age at transplant of 65 years-old (range 60 to70). Two thirds (66%) of patients were male. Based on the R-ISSS score, 46% were stage I, 54% were stage II and none were stage III. HCT-CI score was low, intermediate and high in 40%, 32% and 28% of patients respectively. Median karnofsky index was 90 (range 70 to 100). Acute renal failure was more frequent in the older group (p=0,028) at multiple myeloma diagnostic. Light chain disease was more frequent in the younger patient group with 19% compared to 3% (p=0,09). Mucositis was similar in occurrence in both groups with only 5% of grade ≥3 mucositis. No parenteral alimentation was required in the older patient group while 4 patients required it in the younger patient group(p=0,053). The incidence of febrile neutropenia was universal in all patients (100%) within the cohort. The incidence of septic shock and admission to intensive care unit was only 1%. Delirium was diagnosed in 2 older patients (p=0,131). There was no difference in toxicity profile when comparing both groups. Median engraftment for neutrophils was 14 days and 16 days for platelets. Median hospital stay duration was 21 days. Intravenous antibiotics were used a median time of 8 days. There was no difference in resources used during transplant in both groups. Median CD4 count was comparable in both groups at 3 months and at 1 year after transplant. With a median follow-up of 37 months (range 2 to 70), our cohort had a PFS of 24 months with no difference between younger and older patient groups(p=0,234). The median OS was not reached at the time of evaluation for both groups. Estimated 4 years PFS was 21% and OS was 81%. There was no difference between our younger and older patient cohorts (figure 1 and 2). Being in stable or progressive disease was associated with worse PFS (median of 9 months versus 26 months, p<0,0005)(figure 3). Our 1 year NRM was 0% in both groups.In conclusion, AHSCT is a good treatment option in well-selected patients. Comorbidities must be considered and HCT-CI can help clinicians choose carefully those patients. Our study demonstrates that age should not be the limiting factor when considering ASCT in older patients. Toxicity and survival were comparable in both groups. Best timing when to proceed to ASCT is still in investigation. Considering the significantly worse PFS with chemoresistant disease, other treatment options should be considered before AHSCT without age being a consideration. [Display omitted] DisclosuresDelage:AbbVie: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Pfizer: Research Funding.

Clipping of unruptured cerebral aneurysms : Are older patients at higher risk?

BackgroundThe incidence of aneurysms is steadily increasing in older patients due to the aging population. This study compared radiological parameters as well as clinical outcomes between patients younger than 65 years and those over 65 years of age, with special respect to individual treatment options.MethodsRetrospective data were obtained for patients with cerebral aneurysms at a single academic institution within a 7-year period. Data reviewed included admission protocols, patient charts, operating reports as well as outpatient clinic charts. Aneurysmal characteristics as well as surgical outcome were compared between older patients, defined as patients older than 65 years of age, and a control group of patients younger than 65 years of age. To evaluate and compare individual clinical characteristics various scores including the Hunt and Hess score, the Fisher score, and the Glasgow outcome scale were used.ResultsA total of 347 patients were included in the final analysis. The control group included 290 patients, while 57 patients were in the older patient group. Neither the Hunt and Hess scores nor Fisher scores were significantly correlated to patient age. The Glasgow outcome scale was significantly lower in the older group after clipping of ruptured aneurysms (p < 0.000) but not significantly different after clipping of unruptured aneurysms (p = 0.793).ConclusionPostoperative Glasgow outcome scale scores were not significantly different after clipping of unruptured cerebral aneurysms approximately 1 cm in diameter in older patients compared to the younger age group. Therefore, clipping of unruptured cerebral aneurysms may also be a valuable treatment option for older patients.

Age affects the efficacy of immune checkpoint inhibitors in patients with advanced cancer.

2638 Background: Immune checkpoint inhibitors (ICIs), such as programmed death(ligand)1 (PD-(L)1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, have dramatic effects on treatment in patients with various malignancies. High tumor mutation burden (TMB) is predictive of clinical response to ICI in multiple cancer types. Although age-related immune dysfunction might induce difference on the efficacy of ICIs between younger and older patients, the potential effect of age on the efficacy of ICIs remains little known and controversial. Herein, we aimed to analysis the association between age and the efficacy of ICIs based on MSKCC cohort. Methods: We screened out 1661 patients having complete information with advanced cancer, whose tumors underwent next-generation sequencing (NGS) detection and who were treated with at least one dose of ICI in MSKCC cohort. All patients were divided into two groups according to age, the younger group (age ≤50-year old) and the older group (age &gt; 50-year old). We further analyzed the differences in overall survival (OS) and TMB between the two groups. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated via Cox regression model for OS and P-values were calculated via the Wilcoxon sign test for TMB. We analyzed the effect of age on ICI in lung cancer using the same way. Results: In 1661 patients with cancer in our study, 312 (19%) younger and 1349 (81%) older patients were found. The pooled HRs for OS was 1.28 (95% CI: 1.09-1.52) in younger group compared with older group. In 1661 patients with cancer, there was 350 (21%) patients with lung cancer, including 30 (9%) younger and 320 (91%) older patients. The pooled HRs for OS was 1.45 (95% CI: 0.95-2.23) in younger group compared with older group in lung cancer. In addition, TMB in older group was higher than in younger group and significant difference of TMB was found via the Wilcoxon sign test (p = 2.6e-10) between the two groups, especially in lung cancer (p = 1e-4). Conclusions: Our study assessed the impact of age on the efficacy of ICIs using the threshold of 50 years old for the first time and we founded that patients in older group had higher TMB and longer OS than younger group.

Barriers to initiating SGLT2 inhibitors in diabetic kidney disease: a real-world study

BackgroundSodium-glucose cotransporter 2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g. However, SGLT2i is currently underprescribed among eligible, at-risk patients for CKD progression. We analyzed prescription patterns and barriers to initiating SGLT2i in patients with T2D and CKD in real practice.MethodsA total of 3,703 consecutive outpatients with T2D from four teaching hospitals during six months (2019 ~ 2020) were reviewed. Five eGFR categories (G1, ≥ 90; G2, 60–89; G3ab, 30–59; G4-5, < 30 mL/min/1.73 m2) and three UACR categories (A1, < 30; A2, 30–300; A3, > 300 mg/g) were used to define CKD status.ResultsOverall, 25.8 % patients received SGLT2i in the following eGFR and albuminuria categories: G1 (A1, 31 %; A2, 48 %; A3, 45 %); G2 (A1, 18 %; A2, 24 %; A3, 30%); and G3 (A1, 9 %; A2, 7 %; A3, 13 %).Total prevalence estimate of CKD was 33.8 % (n = 1,253), of whom 25.6 % patients received SGLT2i. We defined eGFR ≥ 45 mL/min/1.73 m2 and UACR ≥ 30 mg/g as high-risk CKD group eligible for SGLT2i (n = 905), of whom 32.9 % patients were treated with an SGLT2i. In this high-risk group, SGLT2i initiation showed negative correlations with age ≥ 65 years and recent hospitalization. Conversely, HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events were positively correlated with SGLT2i initiation.ConclusionsOnly 32.9 % of T2D with CKD eligible for SGLT2i is currently treated with SGLT2i in real-world clinical practice. The older patient group and clinical inertia are the main barriers to initiate SGLT2i for eligible patients. Clinicians should change the glucocentric approach and focus on reducing renal events in T2D.

Real-world data on treatment concepts in classical Hodgkin lymphoma in Sweden 2000-2014, focusing on patients aged>60 years.

Treatment for patients > 60 years with classical Hodgkin lymphoma (cHL) is problematic; there is no gold standard, and outcome is poor. Using the Swedish Lymphoma Registry, we analysed all Swedish patients diagnosed with cHL between 2000 and 2014 (N = 2345; median age 42 years; 691 patients were >60 years). The median follow‐up time was 6.7 years. Treatment for elderly patients consisted mainly of ABVD or CHOP, and the younger patients were treated with ABVD or BEACOPP (with no survival difference). In multivariable analysis of patients > 60 years, ABVD correlated with better survival than CHOP (p = 0.027), and ABVD became more common over time among patients aged 61–70 years (p = 0.0206). Coinciding with the implementation of FDG‐PET/CT, the fraction of advanced‐stage disease increased in later calendar periods, also in the older patient group. Survival has improved in cHL patients > 60 years (p = 0.027), for whom ABVD seems superior to CHOP.

Outcomes of young patients diagnosed with locally advanced rectal cancer.

The incidence of rectal cancer is higher in the older population. In developed nations, there has been a rise in incidence in young onset colorectal cancer (CRC). We examined the outcomes of locally advanced rectal cancer (LARC) in younger patients (yRC) compared with older patients, using a retrospective audit. All cases of LARC referred to two tertiary referral cancer centres in Western Sydney were examined. Patient demographics, presenting symptoms, treatment, relapse free survival (RFS), overall survival (OS) and progression free survival (PFS) were obtained. Under 50 years old was used as the cut-off age for defining yRC. All 145 consecutive patients were treated for LARC, including 28 in the yRC and 117 in the older patient group. Median follow-up was 54 months. yRC were more likely to complete neoadjuvant therapy (100% vs. 86%; P=0.032) and to undergo more extensive surgical procedures (24% vs. 2%, P<0.0001). yRC were more likely to have microsatellite high (MSI) tumours (30% vs. 4.7%; P=0.003). yRC demonstrated significantly poorer RFS compared with the standard group (HR 2.79; median RFS 4.67 vs. 16.02 months; P=0.023). In the relapsed setting, yRC had poorer PFS compared with the standard group (median PFS 2.66 vs. 9.70, P=0.006, HR 3.04). A difference in OS was also seen between the two groups, with yRC demonstrating poorer OS (median OS 40.46 vs. 58.26 months, HR 3.48, P=0.036). Patients under 50 years with LARC are more likely to have MSI tumours with a more aggressive disease course and poorer RFS, PFS and OS. Initiatives to improve early detection of these patients may improve outcomes. Further research is necessary to understand this disease and optimise its treatment.

Der Anästhesiologische Nachbefragungsbogen für Patienten im ambulanten Kontext

The evaluation of German postanesthesia questionnaires is often restricted to inpatient medical care. The anesthesiological questionnaire for patients (ANP) has previously been validated only after medical care of inpatients. Therefore, the aim of the present study was to evaluate the validity of the ANP in the context of outpatient surgery and anesthesia. Data from 4547patients (mean age 18-89 years, sex: m/f, 55%/45%), scheduled for ambulatory orthopedic and trauma surgery, were analyzed. All patients received astandard induction of anesthesia with propofol, sufentanil and 4 mg dexamethasone. Maintenance of anesthesia was achieved with abalanced technique comprising volatile anesthesia (either sevoflurane or desflurane) and sufentanil. In addition, patients undergoing operations on the anterior cruciate ligament received afemoral nerve block with 12-15 ml 0.5% ropivacaine. Of the patients 13% remained in hospital overnight as aresult of complex operations (combined anterior and posterior cruciate ligament repair, hip arthroscopy and 10% of those undergoing shoulder operations). Before discharge from the recovery room, patients were asked to answer questions with respect to postoperative symptoms 1h after anesthesia (ESNA 19items), at the time of interview (ABZ 17items) and about overall patient satisfaction (10items). These results were matched with the type of procedure and time data from the patient administration system. All data were analyzed descriptively using parametrical tests. At both time points, pain in the area of the operation was the predominant symptom (ESNA: 77,1%; ABZ: 74,3%). Pain after shoulder arthroscopy was more severe compared to knee arthroscopy, both with and without repair of the anterior cruciate ligament. Most of the adverse symptoms decreased significantly (p ≤ 0.001) with time, demonstrating progressive recovery of the patient. Patient discomfort was more likely to occur in female than in male patients, and female patients were more likely to be dissatisfied with the progress of recovery. The risk of experiencing adverse symptoms after anesthesia was higher for female than for male patients; this was most apparent for feeling cold (odds ratio, OR 4.08) and nausea and vomiting (OR 3.45). Younger patients (18-40 years) were more likely to express discomfort than both groups of older patients (41-60 years and 61-89 years). Accordingly, younger patients had lower satisfaction levels with respect to both anesthesia and overall perioperative care, and the progress of recovery. Postoperative nausea and vomiting (PONV) were linked to younger age, female sex, and longer procedure times (>40 min). The individual analyses delivered plausible results, which support the validity of the ANP. The ANP may also be used for assessment of postoperative discomfort and patient satisfaction in the setting of outpatient surgery. In view of the short time interval between the two measurement points, the ANP for outpatients could in future be reduced to asingle postoperative questionnaire.

The comparative effects of intensive glucose lowering in diabetes patients aged below or above 65 years: Results from the ADVANCE trial.

For relatively old patients with diabetes, current guidelines recommend adjustment of glycaemic goals based on patients' cognitive function, or coexisting chronic illnesses. However, the evidence which supports the efficacy and safety of intensive glucose lowering in older patients with diabetes is scarce. The objective of the present study was to compare the efficacy and safety of intensive glucose lowering in patients with type 2 diabetes stratified by age (<65 and ≥ 65 years), and examine whether the effects differ according to patients' characteristics in the older patient group. The effects of intensive glucose lowering (to a target glycated haemoglobin [HbA1c] concentration of ≤48 mmol/mol [6.5%]) on major clinical outcomes were evaluated by Cox regression models according to subgroups defined by baseline age of <65 or ≥ 65 years in the ADVANCE trial (n = 11 140). Over a median follow-up of 5 years, intensive glucose lowering significantly decreased the risk of the composite of major macrovascular and microvascular events (hazard ratio 0.90, 95% confidence interval 0.82-0.98), with no heterogeneity in the effects across age subgroups (p for heterogeneity = 0.44). Relative effects on all-cause death, cardiovascular death, and components of major vascular events were also similar (P for heterogeneity ≥0.06), except for severe hypoglycaemia, which was of greater risk for patients aged <65 years. Absolute benefits and harms were broadly consistent across subgroups. Among patients aged ≥65 years, randomized treatment effects did not differ significantly across different levels of cognitive function or coexisting chronic illnesses. Our results suggest that an intensive glycaemic control strategy to reduce HbA1c to 48 mmol/mol (6.5%) provided broadly similar benefits and harms and may be recommended for older, as well as younger, patients.

Dual-center experiences with interventional closure of patent foramen ovale: A medium-term follow-up study comparing two patient groups aged under and over 60 years.

BackgroundCurrent guidelines recommend interventional closure of patent foramen ovale (PFO) in patients with cryptogenic ischemic stroke who are under 60 years of age.HypothesisThe hypothesis of this study was to compare follow‐up results of PFO closure in patients over 60 years of age to those of patients under 60 years of age in order to determine whether the procedure is safe and effective for both age groups.MethodsWe included 293 patients who had a cryptogenic ischemic stroke and a PFO confirmed by transesophageal echocardiography (TEE) and who were scheduled for percutaneous closure of the PFO between 2014 and 2019. The device implantation was completed in all patients using an Amplatzer™, Occlutec™, or Cardia Ultrasept PFO occluder.ResultsFollow‐up TEE examinations were performed at intervals of 1, 3, and 6 months after implantation. Patients were followed for a median of 3.6 ± 1.2 years. Recurrent ischemic stroke or transient ischemic attack, cardiac death, arrhythmias, and residual shunt were reported equally in both groups.ConclusionsInterventional closure of PFO can be as safe and effective in patients over 60 years of age as it is in patients under 60 years of age regardless of the device used. In this older patient group, rigorous discussion and a case‐by‐case decision‐making process including cardiologists and neurologists is warranted to ensure optimal procedure selection.

Comparison of transcatheter aortic valve implantation outcomes in patients younger than 85 years and those aged 85 years or older: a single-center study.

The number of elderly patients requiring treatment of aortic stenosis is expected to grow steadily due to increasing lifespan. Transcatheter aortic valve implantation (TAVI) is an alternative treat‑ ment for patients with aortic stenosis considered nonoptimal candidates for surgical valve replacement. We aimed to assess age‑related differences in 30‑day and 1‑year cardiovascular mortality, Valve Academic Research Consortium‑2 (VARC‑2)-defined complications in patients undergoing TAVI, by comparing outcomes in patients younger than 85 years and those aged 85 years or older. The study group included patients who underwent TAVI at the Institute of Cardiology, Warsaw from January 2009 to July 2019. Clinical, procedural, and follow‑up data were retrospectively collected and compared in 2 groups defined according to age: group 1, younger than 85 years (417) and group 2, aged 85 or older (200). The surgical risk profile assessed by the EuroSCORE II was significantly higher in the group of older patients (median [interquartile range], 6.5% [3.5%-17.3%] vs 7.2% [3.4%-18.1%]; P = 0.002); 30‑day and 1‑year cardiovascular mortality was 4.3% in group 1 as compared with 5% in group 2 (P = 0.69) and 10.8% in group 1 as compared with 9.4% in group 2 (P = 0.51), respectively. The rate of VARC‑2‑defined complications was similar in both groups, with the exception of major vascular com‑ plications (3.12% vs 8.5%; P = 0.004) and major bleeding (10.8% vs 18.5%; P = 0.008), which were more prevalent in older patients. Cardiovascular mortality at 1 month and 1 year following TAVI is similar in patients aged 85 years or older and in those younger than 85 years.

Knee Extension Strength Measures Indicating Probable Sarcopenia Is Associated with Health-Related Outcomes and a Strong Predictor of 1-Year Mortality in Patients Following Hip Fracture Surgery.

To examine if knee-extension strength (KES) measures indicating probable sarcopenia are associated with health-related outcomes and if KES and hand grip strength (HGS) measures are associated with 1-year mortality after hip fracture. Two groups of older patients with hip fracture had either HGS (n = 32) or KES (n = 150) assessed during their acute hospital stay. Cut-points for HGS (<27 kg for men and <16 kg for women), and cut-points for maximal isometric KES (non-fractured limb), being the lowest sex-specific quintile (<23.64 kg for men and <15.24 kg for women), were used to examine association with health-related outcomes and 1-year mortality. Overall, 1-year mortality was 12.6% in the two strength groups, of which 47% (HGS) and 46% (KES) respectively, were classified as probable sarcopenia. Probable sarcopenia patients (KES) had lower prefracture function, performed poorly in mobility measures and expressed a greater concern of falling compared to their stronger counterparts. Hazard ratio for 1-year mortality was 2.7 (95%CI = 0.49–14.7, p = 0.3) for HGS and 9.8 (95%CI = 2.2–43.0, p = 0.002) for KES for probable sarcopenia patients compared to those not. Sex-specific KES measures indicating sarcopenia is associated with health-related outcomes and a strong predictor of 1-year mortality after hip fracture.

Effects of esmolol infusion on cardiovascular parameters and quality of general anaesthesia in younger and older patients

Background: Esmolol is a cardioselective b-adrenergic antagonist that is used during general anaesthesia to blunt the sympathetic reflex tachycardia and hypertension. The aim of the study was to investigate whether the potential beneficial and adverse effects of esmolol differ depending on the patient age. Methods: A total of 50 ASA I/II patients scheduled for elective upper abdominal surgery were divided in two groups: younger (patients aged up to 35 years) and older (patients older than 65). After premedication with Diazepam, they were infused with esmolol during the first 5 min at a rate of 0.3 mg/kg/min and 0.1 mg/kg/min thereafter. Anaesthesia was induced with thiopental sodium 3-5 mg/kg intravenously (iv) and fentanyl 1.5 µg/kg IV. Tracheal intubation was facilitated with suxamethonium 1-2 mg/kg IV. Long-term neuromuscular blockade was induced with pancuronium bromide 0.07 mg/kg IV bolus and maintained with incremental IV boluses of 0.01 mg/ kg. Inhalational anaesthesia was maintained with a mixture of oxygen and nitrous oxide (O2 /N2 O) 2 : 1. Results: The systolic blood pressure remained constant during the intubation phase in the group of older patients, at the same time being around 89 % of the pre-induction values, while in younger patients it rose up to 100 %. During the same phase of anaesthesia, the diastolic blood pressure in older patients remained at about 91 %, while in younger patients it rose up to 107 % of the pre-induction values. The consumption of drugs and the speed and quality of the recovery from anaesthesia did not differ between the two groups of patients. Conclusion: Infusion of esmolol contributes to the concept of general balanced anaesthesia in elective patients scheduled for upper abdominal surgery equally in younger and older patients.

Cytogenetic characteristics of 665 patients with myelodysplastic syndrome in China: A single‑center report

The karyotype is highly important for diagnosis and prognosis in myelodysplastic syndrome (MDS). The objective of the present study was to investigate the cytogenetic characteristics of patients with MDS in China. The karyotypes of 665 Chinese patients with MDS were analyzed, and it was identified that 298 cases (298/665, 44.8%) had abnormal karyotypes. Among the 298 patients with abnormal karyotypes, the 75 patients with trisomy 8 (+8) constituted the most common subset (75/298, 25.2%). The incidence of abnormal karyotypes was significantly higher in patients who were ≥51 years old compared with those <51 years old, (54.8 vs. 34.7%, respectively; P<0.05). Based on World Health Organization (WHO) classification-based Prognostic Scoring System (WPSS) criteria, the incidence of poor-prognosis karyotypes was significantly higher (17.4 vs. 5.4%; P<0.05) in the older patient group, and based on the Revised International Prognostic Scoring System (IPSS-R) criteria, the incidence of poor-/very poor-prognosis karyotypes was also significantly higher (17.4 vs. 6.6%; P<0.05) in patients ≥51 years old compared with younger ones. Based on the WHO classification of MDS subtypes, the incidence of abnormal karyotypes in patients with high percentages of bone marrow (BM) blasts [excess blasts (EB)-I + EB-II, ≥5% blasts] was significantly higher than that in patients with low percentages of BM blasts (those with single lineage dysplasia + multilineage dysplasia, <5% blasts) (62.5 vs. 36.0%; P<0.05). The incidence of poor-prognosis karyotypes based on WPSS criteria was significantly higher in patients with high percentages of BM blasts than those with low percentages (22.0 vs. 6.9%, respectively; P<0.05), and the incidence of poor-/very poor-prognosis karyotypes based on IPSS-R criteria was also significantly higher (23.0 vs. 7.4%, respectively; P<0.05). These results demonstrate that +8 is the most common abnormal karyotype in Chinese patients with MDS. Age and the percentage of BM blasts are associated with the incidence of both abnormal karyotypes and karyotypes with poor prognosis. The results of cytogenetic abnormalities in this study will supplement the data on patients of MDS in China.

Frailty and Initiation of Cardio-Protective Medicines Following Incident Acute Coronary Syndrome in Older People: A Linked Data Study

IntroductionBeta-blockers, renin-angiotensin system inhibitors and statins are evidence-based pharmacotherapies for preventing recurrent acute coronary syndrome (ACS), however their use in older people may depend on clinical factors such as comorbidity and frailty. Deriving comorbidity information from linked administrative data is well established. The recent development of the Hospital Frailty Risk Score (HFRS) now allows ascertainment of frailty from linked administrative data.&#x0D; Objectives and ApproachWe determined the ability of the HFRS to discriminate between groups of older patients initiated on these three cardio-protective medicines following hospitalisation for an incident ACS. We used a 15-year look back to identify incident ACS cases between 2005 and 2008 from Western Australian hospital data and linked them to national pharmaceutical dispensing records. The study was limited to patients aged ≥65 years who had not received these medicines in the last two years and were discharged alive from their index ACS admission. Separate competing risk regression models assessed the association between HFRS and initiation of each medicine, controlling for comorbidities and other variables available from the linked datasets.&#x0D; ResultsOverall, increasing levels of HFRS were associated with lower subdistribution hazards of initiation of each medicine examined, however these varied by age group and sex. For example, the subdistribution hazard ratios (SHR) for beta-blocker initiation among men in the oldest age group (≥85 years) were 0.65 (95% CI: 0.44-0.95) and 0.51 (95% CI: 0.29-0.90) in the intermediate and high HFRS groups respectively compared to the low frailty group. The corresponding SHR for women were 1.01 (95% CI: 0.76-1.35) and 0.89 (95% CI: 0.63-1.27), respectively.&#x0D; Conclusion / ImplicationsThe HFRS applied to linked administrative data discriminates between groups of older people who received cardio-protective medicines following an incident ACS. There is potential for it to be used in other chronic disease conditions.

Age-related fatigue is associated with reduced mitochondrial function in peripheral blood mononuclear cells.

Fatigue is a complex syndrome associated with exhaustion not relieved by sleep. It occurs frequently in older adults in the context of chronic disease and is associated with decreased physical capacity. Whether a mitochondrial dysfunction and therefore an impaired energy production might contribute to the development of fatigue during aging is yet unknown. The aim of this study was to evaluate mitochondrial respiration of peripheral blood mononuclear cells (PBMCs) in older patients with and without fatigue. Fatigue was determined according to the Brief Fatigue Inventory. Mitochondrial respiration of freshly isolated PBMCs was investigated by high-resolution respirometry using the Oroboros Oxygraph-O2k. Functional impairment and depressive symptoms were assessed using questionnaires. 23 geriatric patients (77.8±4.9years; 43.5% female) with fatigue and 22 without fatigue (75.4±5.4years; 45.5% female) were analyzed. Patients with fatigue exhibited more functional limitations and more depressive symptoms. High-resolution respirometry of intact PBMCs revealed a lower routine (4.82±1.14pmol/s versus 5.89±1.90pmol/s, p=0.041) and maximum (6.55±1.51pmol/s versus 8.43±3.67pmol/s, p=0.013) oxygen consumption rate, resulting in a reduced ATP-linked respiration (4.26±1.00pmol/s versus 5.09±1.53pmol/s, p=0.035) of PBMCs from geriatric patients with fatigue compared to controls without. This short report shows that in this group of older patients, fatigue is associated with lower PBMC mitochondrial respiration. Whether the impaired mitochondrial respiration is accompanied by a reduced mitochondrial activity in other organs (e.g. muscle) remains to be elucidated.

Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Older Versus Younger Patients

Introduction: Previous studies have demonstrated that allogeneic haploidentical (haplo) peripheral blood stem cell transplantation (PBSCT) with post-transplant cyclophosphamide (PTCy) yields improved progression free survival (PFS) when compared to haplo bone marrow transplant (BMT) with PTCy, attributable to lower relapse without an increase in non-relapse mortality (NRM) (Bashey, et al. JCO. 2017). However, haplo PBSCT results in higher rates of graft-versus-host disease (GVHD) which may negate these benefits in older patients who are more susceptible to transplant related toxicity. Thus, evaluation of the outcomes of haplo PBSCT with PTCy in older patients is warranted. Methods: We retrospectively evaluated 121 adult patients with hematologic malignancies treated at the Moffitt Cancer Center with allogeneic T-cell replete PBSCT from a haplo donor followed by PTCy-based GVHD prophylaxis. Data were extracted from the Moffitt BMT Research &amp; Analysis Information Network (BRAIN) database. Myeloablative (n=70, 58%) and reduced intensity (n=51, 42%) conditioning regimens were included. Transplant related outcomes were compared between two age groups: &amp;lt;60 years (n=66) versus &amp;gt;60 years (n=55). Associations with transplant related survival outcomes were assessed using univariate and multivariate Cox proportional hazard survival models. Fine and Gray regression models were used to assess associations of transplant related endpoints with competing risks. Kaplan-Meier curves and cumulative incidence function curves were also plotted. Results: The median age at the time of transplant was 42 years (range: 20-59) for the younger group and 66 years (range: 61-75) for the older group. The median follow-up was 17 months (range: 2-53) for the entire cohort. Younger patients were more likely to receive myeloablative conditioning (83% versus 27%, p&amp;lt;0.001). Baseline characteristics were otherwise similar. Neutrophil engraftment (&amp;gt;500/uL) by day 30 did not differ significantly between the younger and older group (98% versus 93%, p=0.26). However, the median time to neutrophil engraftment was faster in the younger group versus the older group (16 versus 21 days, p&amp;lt;0.001). Platelet engraftment (&amp;gt;20,000/uL) by day 90 was achieved in 92% in the younger group versus 76% in the older group (p=0.03). The time to platelet engraftment was faster in the younger group: 28 days versus 36 days (p=0.006). At day 100, the cumulative incidence (CuI) of grade II-IV acute GVHD in younger patients was 42% (95% CI 29-61%) and for older patients was 35% (95% CI 22-55%, p=0.82). The CuI for grade III-IV acute GVHD for the younger and the older groups were 8% (95% CI 4-25%) and 15% (95% CI 7-38%, p=0.23), respectively. At 2 years, the CuI of chronic GVHD was 67% (95% CI 55-82%) for younger patients versus 56% (95% CI 38-82%) for older patients (p=0.20). NRM for the younger group and the older group, respectively, was 6% (95% CI 2-16%) versus 19% (95% CI 11-34%) at 100 days and 14% (95% CI 6-30%) versus 22% (95% CI 13-37%) at 2 years (p=0.17). The CuI of relapse at 2 years was not significantly different between the two age groups, with the younger recipients having a CuI of 42% (95% CI 20-60%) and the older group 31% (95% CI 17-56%, p=0.70). The 2-year DFS was similar between the younger and older group, respectively: 51% (95% CI 36-66%) and 53% (95% CI 37-70%, p=0.72). Similarly 2-year overall survival (OS) for the younger group was 59% (95% CI 44-74%), while the older group was 66% (95% CI 52-80%, p=0.92). In multivariate analysis, NRM was superior in the younger group (HR=0.31, 95% 0.12-0.82, p=0.02). Otherwise, age was not associated with engraftment, risk of acute or chronic GVHD, relapse, DFS, or OS. Conclusion: Our results demonstrate that outcomes following allogeneic haplo PBSCT with PTCy in patients &amp;gt;60 years approximate outcomes in patients &amp;lt;60 years. While NRM was inferior in the older patient group, this difference did not result in significant differences in long term OS or DFS. Instead, other variables such as the hematopoietic comorbidity index and the disease risk index were better indicators of survival outcomes. Additionally, these survival outcomes with haplo PBSCT with PTCy appear to be similar to prior published data with haplo BMT with PTCy in older patients (Kasamon, et al. JCO. 2015). Based on this study, haplo PBSCT with PTCy is an appropriate transplant platform for elderly patients. Disclosures Khimani: Bristol Myers Squibb-Moffitt-Alliance: Research Funding. Nishihori:Novartis: Other: Research support to institution; Karyopharm: Other: Research support to institution. Pidala:Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Johnson and Johnson: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding; BMS: Research Funding. Bejanyan:Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees.

Evaluation of the effect of older age on the diagnostic specificity of high-sensitivity troponin I and high-sensitivity troponin T in patients with suspected acute myocardial infarction

Abstract Background Cardiac troponins have become the gold standard for appropriate and rapid diagnosis of an acute myocardial infarction (AMI). However, elevated cardiac troponins levels can be observed in the absence of AMI in elderly patients and therefore a loss of specificity is seen in the diagnosis of AMI in elderly patients. Purpose This study aims to define old age in suspected AMI and to evaluate the effect of older age on the diagnostic specificity of a high sensitivity troponin I (hs-cTnI) and high sensitivity troponin T (hs-cTnT) assay in elderly women and men. Methods This study used data from patients with suspected AMI who were enrolled between 08–2011 and 10–2016 to a multicentre biomarker registry and an University Hospital and with available hs-cTnI and hs-cTnT upon admission (n=564 patients). First, we investigated the effect of age on the specificity of both hs-cTnI and hs-cTnT to detect AMI continuously. We then classified over seventy-year-olds as elderly (n=281; 49,8%) and compared the specificity of hs-cTnI and hs-cTnT between elderly and younger patients. Results In the group of older patients, 62.6% (n=176) were diagnosed with AMI compared with 50.9% (n=144) in younger age patients (p&amp;lt;0.01). Elderly patients had higher median levels of hs-cTnI and hs-cTnT than younger patients: 45.4 ng/L vs. 13.1 ng/L hs-cTnI (p&amp;lt;0.001) and 36.8 ng/L vs. 12.8 ng/L hs-cTnT (p&amp;lt;0.001) irrespective of the final diagnosis. Figure1 shows a shift in diagnostic specificity for the whole troponin concentration range in elderly patients compared to younger patients starting at the age of 60 years with clear impact in patients older than 70 years used as threshold for old age in further analyses. Applying the 99th percentile cut-off led to a specificity of 93.5% (95% CI: 88.1–97.0%) in younger patients vs. 88.6% (95% CI: 80.9–94.0%) in elderly patients for hs-cTnI and of 91.4% (95% CI: 85.4–95.5%) vs. 65.7% (95% CI: 55.8–74.7%) for hs-cTnT. To achieve the same specificity in elderly patients as in younger patients, optimized rule-in cut-offs were calculated with 2.6-fold of the 99th percentile for hs-cTnI (68.9 ng/L) and 3.1-fold of the 99th percentile for hs-TnT (43.9 ng/L). Conclusions The specificity of both, hs-cTnI and hs-cTnT is significantly reduced in elderly patients due to higher hs-cTnT and hs-cTnI levels in elderly patients at admission irrespective of the final diagnosis. A relevant loss in diagnostic specificity is observed at 70 years of age starting already at 60 years. Use of assay-specific adjusted cut-offs for hs-cTnI and hs-cTnT for elderly patients regains diagnostic specificity that leads to a more accurate decision-making concerning “rule-in” for older patients with suspected AMI. Funding Acknowledgement Type of funding source: None

Unraveling Ariadne's Thread Into the Labyrinth of aMCI: Depression and Financial Capacity.

People with amnestic mild cognitive impairment (aMCI) face many daily challenges as memory loss is their predominant cognitive impairment. This study examined whether financial capacity can be influenced by comorbid depression in patients with multiple-domain aMCI. The participants included 120 patients in 4 groups: multiple-domain aMCI with and without depressive symptoms, and nondemented elders with and without depression. Participants were examined with the Mini-Mental State Examination, the 15-item Geriatric Depression Scale, and the Legal Capacity for Property Law Transactions Assessment Scale. The findings extend earlier work in other groups of older patients and indicate that the performance of patients with multiple-domain aMCI in cognitive functioning and financial capacity is severely impaired when depression coexists, resembling the performance of patients with mild Alzheimer disease. The results support special care for individuals with depression as this condition severely influences financial capacity in aMCI.

Histopathologic Correlates of Kidney Function: Insights From Nephrectomy Specimens

Existing data sets correlating kidney histopathologic findings with kidney function have low proportions of elderly patients (and those with a family history of kidney failure are over-represented), which limits their generalizability. Our objective was to use non-neoplastic tissue from nephrectomy specimens to examine the association between degree of histopathologic changes and estimated glomerular filtration rate (eGFR) and determine whether the association differed by age. Cross-sectional study. Glomerulosclerosis (GS), interstitial fibrosis/tubular atrophy (IFTA), and arterial sclerosis/arteriosclerosis (AS). eGFR. We retrospectively reviewed kidney pathology reports (of non-neoplastic tissue) from 1,347 patients who underwent nephrectomy (1999-2018) for any indication but most commonly due to kidney cancer. We evaluated the association between degree of GS, IFTA, and AS with eGFR at the time of nephrectomy and whether this was modified by age. Among the participants (aged 17-91 years), 42% and 57.8% had>10% GS and IFTA, respectively, and 81.8% had moderate or severe AS. We found that greater degrees of GS, IFTA, and AS were associated with lower eGFR after multivariable adjustment. Although there was a greater prevalence of more severe degrees of GS and IFTA in older individuals, the association between various histopathologic features and eGFR was not modified by age. Retrospective cross-sectional study. Our study demonstrates differences in the histologic appearance of the kidneys across levels of eGFR. Although the prevalence of advanced changes was higher in the oldest group of patients, a subset had excellent kidney function and limited histologic changes.