RESUMO
Defective host defenses later in life are associated with changes in immune cell activities, suggesting that age-specific considerations are needed in immunotherapy approaches. In this study, we found that PD-1 and CTLA4-based cancer immunotherapies are unable to eradicate tumors in elderly mice. This defect in anti-tumor activity correlated with two known age-associated immune defects: diminished abundance of systemic naive CD8+ T cells and weak migratory activities of dendritic cells (DCs). We identified a vaccine adjuvant, referred to as a DC hyperactivator, which corrects DC migratory defects in the elderly. Vaccines containing tumor antigens and DC hyperactivators induced T helper type 1 (TH1) CD4+ T cells with cytolytic activity that drive anti-tumor immunity in elderly mice. When administered early in life, DC hyperactivators were the only adjuvant identified that elicited anti-tumor CD4+ T cells that persisted into old age. These results raise the possibility of correcting age-associated immune defects through DC manipulation.
Assuntos
Linfócitos T CD4-Positivos , Células Dendríticas , Camundongos Endogâmicos C57BL , Células Dendríticas/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Camundongos , Envelhecimento/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunoterapia/métodos , Vacinas Anticâncer/imunologia , Feminino , Neoplasias/imunologia , Neoplasias/terapia , Receptor de Morte Celular Programada 1/metabolismo , Antígeno CTLA-4/metabolismo , Movimento Celular , Antígenos de Neoplasias/imunologiaRESUMO
BCG vaccination in children protects against heterologous infections and improves survival independently of tuberculosis prevention. The phase III ACTIVATE trial assessed whether BCG has similar effects in the elderly. In this double-blind, randomized trial, elderly patients (n = 198) received BCG or placebo vaccine at hospital discharge and were followed for 12 months for new infections. At interim analysis, BCG vaccination significantly increased the time to first infection (median 16 weeks compared to 11 weeks after placebo). The incidence of new infections was 42.3% (95% CIs 31.9%-53.4%) after placebo vaccination and 25.0% (95% CIs 16.4%-36.1%) after BCG vaccination; most of the protection was against respiratory tract infections of probable viral origin (hazard ratio 0.21, p = 0.013). No difference in the frequency of adverse effects was found. Data show that BCG vaccination is safe and can protect the elderly against infections. Larger studies are needed to assess protection against respiratory infections, including COVID-19 (ClinicalTrials.gov NCT03296423).
Assuntos
Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Infecções Respiratórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/administração & dosagem , Método Duplo-Cego , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/imunologia , Viroses/imunologia , Viroses/prevenção & controleRESUMO
Addressing the total energy cost burden of elderly people is essential for designing equitable and effective energy policies, especially in responding to energy crisis in an aging society. It is due to the double impact of energy price hikes on households-through direct impact on fuel bills and indirect impact on the prices of goods and services consumed. However, while examining the household energy cost burden of the elderly, their indirect energy consumption and associated cost burden remain poorly understood. This study quantifies and compares the direct and indirect energy footprints and associated total energy cost burdens for different age groups across 31 developed countries. It reveals that the elderly have larger per capita energy footprints, resulting from higher levels of both direct and indirect energy consumption compared with the younger age groups. More importantly, the elderly, especially the low-income elderly, have a higher total energy cost burden rate. As the share of elderly in the total population rapidly grows in these countries, the larger per capita energy footprint and associated cost burden rate of elderly people would make these aging countries more vulnerable in times of energy crises. It is therefore crucial to develop policies that aim to reduce energy consumption and costs, improve energy efficiency, and support low-income elderly populations. Such policies are necessary to reduce the vulnerability of these aging countries to the energy crisis.
Assuntos
Características da Família , Pobreza , Humanos , Idoso , Países Desenvolvidos , Envelhecimento , Política PúblicaRESUMO
BACKGROUND: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC). METHODS: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min-1·1.73 m-2 or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events. RESULTS: Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61). CONCLUSIONS: Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications. REGISTRATION: URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study).
Assuntos
Fibrilação Atrial , Fragilidade , Acidente Vascular Cerebral , Tromboembolia , Humanos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Idoso Fragilizado , Fragilidade/diagnóstico , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Vitamina K , Administração Oral , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) infection is gaining interest due to the recent development of vaccines, but it is still misdiagnosed in the elderly. The primary objective was to compare all-cause mortality at day 30. Secondary objectives were to compare clinical presentation, and rates of consolidative pneumonia, hospitalization, and intensive care unit (ICU) admission. METHODS: Single-centre retrospective study conducted in a French university hospital during 7 epidemic seasons. All patients aged ≥75 years were included. RESULTS: 558 patients were included: 125 with RSV and 433 with Influenza. Median age was 84.8 years. RSV patients had more respiratory symptoms (wheezing, dyspnea), whereas Influenza patients had more general symptoms (fever, asthenia, myalgia). Consolidative pneumonia (28.8% vs. 17.2%; p = 0.004), hospitalization rates (83.2% vs. 70%; p = 0.003), ICU admissions (7.2% vs. 3.0%; p = 0.034) and length of stay (9 days [2-16] vs. 5 days [0-12]; p = 0.002), were higher in the RSV group. Mortality rates at day 30 were comparable (RSV 9.6%, Influenza 9.7%; p = 0.973). CONCLUSIONS: This study included the largest cohort of RSV-infected patients aged over 75, documented in-depth thus far. RSV shares a comparable mortality rate with Influenza but is associated with higher rates of consolidative pneumonia, hospitalization, ICU admissions, and extended hospital stays.
RESUMO
Over 2.5 million gastrointestinal endoscopic procedures are carried out in the United Kingdom (UK) every year. Procedures are carried out with local anaesthetic r with sedation. Sedation is commonly used for gastrointestinal endoscopy, but the type and amount of sedation administered is influenced by the complexity and nature of the procedure and patient factors. The elective and emergency nature of endoscopy procedures and local resources also have a significant impact on the delivery of sedation. In the UK, the vast majority of sedated procedures are carried out using benzodiazepines, with or without opiates, whereas deeper sedation using propofol or general anaesthetic requires the involvement of an anaesthetic team. Patients undergoing gastrointestinal endoscopy need to have good understanding of the options for sedation, including the option for no sedation and alternatives, balancing the intended aims of the procedure and reducing the risk of complications. These guidelines were commissioned by the British Society of Gastroenterology (BSG) Endoscopy Committee with input from major stakeholders, to provide a detailed update, incorporating recent advances in sedation for gastrointestinal endoscopy.This guideline covers aspects from pre-assessment of the elective 'well' patient to patients with significant comorbidity requiring emergency procedures. Types of sedation are discussed, procedure and room requirements and the recovery period, providing guidance to enhance safety and minimise complications. These guidelines are intended to inform practising clinicians and all staff involved in the delivery of gastrointestinal endoscopy with an expectation that this guideline will be revised in 5-years' time.
Assuntos
Gastroenterologia , Propofol , Humanos , Sedação Consciente , Endoscopia Gastrointestinal/efeitos adversos , Endoscopia Gastrointestinal/métodos , BenzodiazepinasRESUMO
Cognitive impairment induced by postoperative pain severely deteriorates the rehabilitation outcomes in elderly patients. The present study focused on the relationship between microglial exosome miR-124-3p in hippocampus and cognitive impairment induced by postoperative pain. Cognitive impairment model induced by postoperative pain was constructed by intramedullary nail fixation after tibial fracture. Morphine intraperitoneally was carried out for postoperative analgesia. Morris water maze tests were carried out to evaluate the cognitive impairment, while mRNA levels of neurotrophic factors (BDNF, NG) and neurodegenerative biomarker (VILIP-1) in hippocampus were tested by q-PCR. Transmission electron microscope was used to observe the axon degeneration in hippocampus. The levels of pro-inflammatory factors (TNF-α, IL-1ß, IL-6), the levels of anti-inflammatory factors (Ym, Arg-1, IL-10) and microglia proliferation marker cyclin D1 in hippocampus were measured to evaluate microglia polarization. Bioinformatics analysis was conducted to identify key exosomes while BV-2 microglia overexpressing exosome miR-124-3p was constructed to observe microglia polarization in vitro experiments. Exogenous miR-124-3p-loaded exosomes were injected into hippocampus in vivo. Postoperative pain induced by intramedullary fixation after tibial fracture was confirmed by decreased mechanical and thermal pain thresholds. Postoperative pain induced cognitive impairment, promoted axon demyelination, decreased BDNF, NG and increased VILIP-1 expressions in hippocampus. Postoperative pain also increased pro-inflammatory factors, cyclin D1 and decreased anti-inflammatory factors in hippocampus. However, these changes were all reversed by morphine analgesia. Bioinformatics analysis identified the critical role of exosome miR-124-3p in cognitive impairment, which was confirmed to be down-regulated in hippocampus of postoperative pain mice. BV-2 microglia overexpressing exosome miR-124-3p showed decreased pro-inflammatory factors, cyclin D1 and increased anti-inflammatory factors. In vivo, stereotactic injection of exogenous miR-124-3p into hippocampus decreased pro-inflammatory factors, cyclin D1 and increased anti-inflammatory factors. The cognitive impairment, axon demyelination, decreased BDNF, NG and increased VILIP-1 expressions in hippocampus were all alleviated by exogenous exosome miR-124-3p. Microglial exosome miR-124-3p in hippocampus alleviates cognitive impairment induced by postoperative pain through microglia polarization in elderly mice.
Assuntos
Disfunção Cognitiva , Doenças Desmielinizantes , Exossomos , MicroRNAs , Fraturas da Tíbia , Animais , Camundongos , Anti-Inflamatórios/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Ciclina D1/metabolismo , Doenças Desmielinizantes/metabolismo , Exossomos/metabolismo , Hipocampo/metabolismo , Microglia/metabolismo , MicroRNAs/genética , Derivados da Morfina/metabolismo , Dor Pós-Operatória/metabolismo , Fraturas da Tíbia/metabolismo , EnvelhecimentoRESUMO
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (H3/IDH-wt-pHGG) is a newly defined entity amongst brain tumours, primarily reported in children. It is a rare, ill-defined type of tumour and the only method to diagnose it is DNA methylation profiling. The case we report here carries new knowledge about this tumour which may, in fact, occur in elderly patients, be devoid of evocative genomic abnormalities reported in children and harbour a misleading mutation.
Assuntos
Neoplasias Encefálicas , Glioma , Substância Branca , Idoso , Feminino , Humanos , Criança , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Genômica , Lobo Occipital/diagnóstico por imagemRESUMO
BACKGROUND: Data are limited on influenza vaccine effectiveness (VE) in the prevention of influenza-related hospitalizations in older adults and those with underlying high-risk comorbidities. METHODS: We conducted a prospective, test-negative, case-control study at 2 US hospitals from October 2018-March 2020 among adults aged ≥50 years hospitalized with acute respiratory illnesses (ARIs) and adults ≥18 years admitted with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) exacerbations. Adults were eligible if they resided in 1 of 8 counties in metropolitan Atlanta, Georgia. Nasopharyngeal and oropharyngeal swabs were tested using BioFire FilmArray (bioMérieux, Inc.) respiratory panel, and standard-of-care molecular results were included when available. Influenza vaccination history was determined from the Georgia vaccine registry and medical records. We used multivariable logistic regression to control for potential confounders and to determine 95% confidence intervals (CIs). RESULTS: Among 3090 eligible adults, 1562 (50.6%) were enrolled. Of the 1515 with influenza vaccination history available, 701 (46.2%) had received vaccination during that season. Influenza was identified in 37 (5.3%) vaccinated versus 78 (9.6%) unvaccinated participants. After adjustment for age, race/ethnicity, immunosuppression, month, and season, pooled VE for any influenza-related hospitalization in the eligible study population was 63.1% (95% CI, 43.8-75.8%). Adjusted VE against influenza-related hospitalization for ARI in adults ≥50 years was 55.9% (29.9-72.3%) and adjusted VE against influenza-related CHF/COPD exacerbation in adults ≥18 years was 80.3% (36.3-93.9%). CONCLUSIONS: Influenza vaccination was effective in preventing influenza-related hospitalizations in adults aged ≥50 years and those with CHF/COPD exacerbations during the 2018-2020 seasons.
Assuntos
Insuficiência Cardíaca , Vacinas contra Influenza , Influenza Humana , Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Estudos de Casos e Controles , Estudos Prospectivos , Pandemias , Eficácia de Vacinas , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Insuficiência Cardíaca/epidemiologia , Vacinação , Hospitalização , Estações do AnoRESUMO
BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.
RESUMO
Despite vaccination programs, pertussis has been poorly controlled, especially among older adults in Australia. This longitudinal, retrospective, observational study aimed to estimate the incidence and risk factors of pertussis among persons ≥50 years of age in Australia in the primary care setting, including those with underlying chronic obstructive pulmonary disease (COPD) or asthma. We used the IQVIA general practitioner electronic medical record database to identify patients ≥50 years of age with a clinical diagnosis of pertussis during 2015-2019. Pertussis incidence rates ranged from 57.6 to 91.4 per 100,000 persons and were higher among women and highest in those 50-64 years of age. Patients with COPD or asthma had higher incidence rates and an increased risk for pertussis compared with the overall population ≥50 years of age. Our findings suggest that persons ≥50 years of age in Australia with COPD or asthma have a higher incidence of and risk for pertussis diagnosis.
Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Coqueluche , Idoso , Feminino , Humanos , Asma/epidemiologia , Austrália/epidemiologia , Incidência , Estudos Retrospectivos , Fatores de Risco , Coqueluche/epidemiologiaRESUMO
We assessed SARS-CoV-2 seroprevalence in Japan during July-August 2023, with a focus on 2 key age groups, 0-15 and >80 years. We estimated overall seroprevalence of 45.3% for nucleocapsid antibodies and 95.4% for spike antibodies and found notable maternally derived spike antibodies in infants 6-11 months of age (90.0%).
Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/imunologia , Estudos Soroepidemiológicos , Japão/epidemiologia , SARS-CoV-2/imunologia , Lactente , Criança , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Pré-Escolar , Adulto , Adolescente , Adulto Jovem , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Idoso de 80 Anos ou mais , Recém-Nascido , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
Because of the common physical condition, reduced organ function, and comorbidities, elderly patients with nasopharyngeal carcinoma (NPC) are often underrepresented in clinical trials. The optimal treatment of elderly patients with locally advanced NPC remains unclear. The purpose of this study was to evaluate the efficacy of concurrent nimotuzumab combined with intensity-modulated radiotherapy (IMRT) in elderly patients with locally advanced NPC. We conducted a single-arm, phase II trial for elderly patients with stage III-IVA NPC (according to UICC-American Joint Committee on Cancer TNM classification, 8th edition). All patients received concurrent nimotuzumab (200 mg/week, 1 week prior to IMRT) combined with IMRT. The primary end-point was complete response (CR) rate. The secondary end-points were survival, safety, and geriatric assessment. Between March 13, 2017 and November 12, 2018, 30 patients were enrolled. In total, 20 (66.7%) patients achieved CR, and objective response was observed in 30 (100.0%) patients 1 month after radiotherapy. The median follow-up time was 56.05 months (25th-75th percentile, 53.45-64.56 months). The 5-year locoregional relapse-free survival, distant metastasis-free survival, cancer-specific survival, disease-free survival, and overall survival were 89.4%, 86.4%, 85.9%, 76.5%, and 78.8%, respectively. Grade 3 mucositis occurred in 10 (33%) patients and grade 3 pneumonia in 3 (10%) patients. Concurrent nimotuzumab combined with IMRT is effective and well-tolerated for elderly patients with locally advanced NPC.
Assuntos
Anticorpos Monoclonais Humanizados , Quimiorradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Feminino , Idoso , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Quimiorradioterapia/métodos , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais , Resultado do Tratamento , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagemRESUMO
Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy. Nine months after the transplant, the patient is alive with a functioning graft and no evidence of acute rejection or tumor recurrence.
Assuntos
Neoplasias Hepáticas , Transplante de Fígado , Idoso de 80 Anos ou mais , Humanos , Idoso , Pessoa de Meia-Idade , Centenários , Morte Encefálica , Sobrevivência de Enxerto , Recidiva Local de Neoplasia , Doadores de TecidosRESUMO
Overwhelming evidence has shown that aging is a significant risk factor for COVID-19-related hospitalizations, death and other adverse health outcomes. Particular T cell subsets that susceptible to aging and associated with COVID-19 disease severity requires further elucidation. Our study recruited 57 elderly patients with acute COVID-19 and 27 convalescent donors. Adaptive immunity was assessed across the COVID-19 severity spectrum. Patients underwent age-dependent CD4+ T lymphopenia, preferential loss of circulating T follicular regulatory cells (cTfh) subsets including cTfh-em, cTfh-cm, cTfh1, cTfh2, cTfh17 and circulating T follicular regulatory cells (cTfr), which regulated antibody production through different pathways and correlated with COVID-19 severity, were observed. Moreover, vaccination improved cTfh-cm, cTfh2, cTfr proportion and promoted NAb production. In conclusion, the elderly had gone through age-dependent cTfh subsets deficiency, which impeded NAb production and enabled aggravation of COVID-19 to critical illness, whereas SARS-CoV-2 vaccine inoculation helped to rejuvenate cTfh, cTfr and intensify NAb responses.
Assuntos
COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Células T Auxiliares Foliculares , Humanos , COVID-19/imunologia , Idoso , Masculino , Feminino , SARS-CoV-2/imunologia , Células T Auxiliares Foliculares/imunologia , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Linfócitos T Reguladores/imunologia , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Fatores Etários , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Imunidade Adaptativa/imunologiaRESUMO
Uncertainty remains regarding the safety and tolerability of immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) and cyclosporine (CSA) in older patients. We retrospectively analysed two prospective clinical trials of IST in treatment-naïve severe aplastic anaemia (SAA) to assess safety in older compared to younger patients. Patients ≥18 years of age who had received IST with ATG and CSA +/- eltrombopag (EPAG) were included. Pre-treatment baseline characteristics and co-morbidities were assessed as predictors of therapy-related complications in younger (<60 years) versus older (≥60 years) patients. Out of 245 eligible patients, 54 were older and 191 were younger. Older patients had a similar frequency of SAEs, ICU admissions and hospital length of stay compared to younger patients. Older patients had a higher frequency of cardiac events related to IST, but none resulted in death. Older patients had worse long-term overall survival, and more relapse and clonal evolution post-IST. However, older patients who responded to IST had a similar survival at a median follow-up to younger patients. Disease-related factors and limited therapeutic options in refractory disease likely contribute to poorer outcomes in older patients, not complications of upfront IST. Therefore, IST should be considered first-line therapy for most older SAA patients.
RESUMO
Improving outcomes for older patients with acute myeloid leukaemia remains an unmet need. As part of the LI-1 trial, we evaluated lenalidomide (LEN) in combination with low-dose cytosine arabinoside (LDAC) in patients aged >60 years unfit for intensive therapy and compared this to LDAC alone. Two hundred and two patients, randomised 1:1, were evaluable. Overall response rate (CR + CRi) was higher for LDAC + LEN versus LDAC (26% and 13.7% respectively p = 0.031). However, there was no difference in overall survival between the arms (14% and 11.5% at 2 years for LDAC + LEN and LDAC respectively). The addition of LEN was associated with increased toxicity and supportive care requirements.
Assuntos
Citarabina , Leucemia Mieloide Aguda , Humanos , Idoso , Lenalidomida/uso terapêutico , Indução de Remissão , Leucemia Mieloide Aguda/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high-dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end-point was a 2-year progression-free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60-81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty-six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow-up duration of 36.0 months, the 2-year PFS rate was 58.7%. Treatment was generally well-tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. The 2-year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high-dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab.
RESUMO
BACKGROUND: Few studies have assessed the comprehensive associations among comorbid diseases in elderly patients with nasopharyngeal carcinoma (NPC). This study sought to identify potential comorbidity patterns and explore the relationship of comorbidity patterns with the mortality risk in elderly patients with NPC. METHODS: A total of 452 elderly patients with NPC were enrolled in the study. The network analysis and latent class analysis were applied to mine comorbidity patterns. Propensity score matching was used for adjusting confounders. A restricted cubic spline model was used to analyze the nonlinear association between age and the risk of all-cause mortality. RESULTS: We identified 2 comorbidity patterns, metabolic disease-related comorbidity (MDRC) and organ disease-related comorbidity (ODRC) in elderly patients with NPC. Patients in MDRC showed a significantly higher risk of all-cause mortality (71.41% vs 87.97%, HR 1.819 [95% CI, 1.106-2.994], Pâ =â .031) and locoregional relapse (68.73% vs 80.88%, HR 1.689 [95% CI, 1.055-2.704], Pâ =â .042). Moreover, in patients with MDRC pattern, we observed an intriguing inverted S-shaped relationship between age and all-cause mortality among patients aged 68 years and older. The risk of mortality up perpetually with age increasing in ODRC group, specifically within the age range of 68-77 years (HR 4.371, 1.958-9.757). CONCLUSION: Our study shed light on the potential comorbidity patterns in elderly patients with NPC, thereby providing valuable insights into the development of comprehensive health management strategies for this specific population.
Assuntos
Comorbidade , Carcinoma Nasofaríngeo , Humanos , Masculino , Idoso , Feminino , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/epidemiologia , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICI) applied in patients with melanoma in an adjuvant setting have proven safety and efficacy in several studies, but data on elderly patients aged 75 years or more is scarce. Aim of this study was to investigate efficacy and safety of adjuvant ICI in patients aged ≥ 75 years compared to patients < 75 years in a real-world setting. METHODS: We retrospectively analyzed clinical data, including occurrence of immune-related adverse events (irAE) and outcome of 456 patients that had been treated with adjuvant ICI between January 1st, 2018 and December 20th, 2022. We then compared patients aged ≥ 75 years (n = 117) to patients < 75 years (n = 339) in terms of safety and disease-free survival (DFS). RESULTS AND CONCLUSION: ICI were well tolerated in both groups, with no significant difference observed in the overall occurrence of irAE. However, within the elderly subgroup, there was a significantly higher proportion of skin or nephrological toxicity and colitis/diarrhea compared to the other group. In terms of efficacy, a significantly shorter DFS in patients aged ≥ 75 years was observed. Adjuvant ICI in patients ≥ 75 years was less effective and furthermore associated with an increased risk for skin, renal or bowel toxicity. Therefore, in elderly patients, adjuvant ICI should be used with precaution.