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Chemotherapy is still the main therapeutic strategy for gastric cancer (GC). However, most patients eventually acquire multidrug resistance (MDR). Hyperactivation of the EGFR signaling pathway contributes to MDR by promoting cancer cell proliferation and inhibiting apoptosis. We previously identified the secreted protein CGA as a novel ligand of EGFR and revealed a CGA/EGFR/GATA2 positive feedback circuit that confers MDR in GC. Herein, we outline a microRNA-based treatment approach for MDR reversal that targets both CGA and GATA2. We observed increased expression of CGA and GATA2 and increased activation of EGFR in GC samples. Bioinformatic analysis revealed that miR-107 could simultaneously target CGA and GATA2, and the low expression of miR-107 was correlated with poor prognosis in GC patients. The direct interactions between miR-107 and CGA or GATA2 were validated by luciferase reporter assays and Western blot analysis. Overexpression of miR-107 in MDR GC cells increased their susceptibility to chemotherapeutic agents, including fluorouracil, adriamycin, and vincristine, in vitro. Notably, intratumor injection of the miR-107 prodrug enhanced MDR xenograft sensitivity to chemotherapies in vivo. Molecularly, targeting CGA and GATA2 with miR-107 inhibited EGFR downstream signaling, as evidenced by the reduced phosphorylation of ERK and AKT. These results suggest that miR-107 may contribute to the development of a promising therapeutic approach for the treatment of MDR in GC.
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BACKGROUND: Chromogranin A (CgA) seems to be involved in the pathophysiology of different neurodegenerative pathologies such as Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB). CgA is present in the aggregates of amyloid plaques and in Lewy bodies but CgA also has a function in neuroinflammatory processes via microglia. Our objective was to determine if there is a difference in the CgA concentration in the cerebrospinal fluid (CSF) of AD and DLB patients and whether the CgA concentration can discriminate between the two diseases. METHODS: Using the previously described AlphaLewyMA cohort, we included 117 patients with a CSF CgA assay: 15 control subjects (CS group), 64 DLB patients, 17 AD patients and 21 patients with both AD and probable DLB criteria (AD/DLB group). CgA concentration was assessed using the MSD platform. RESULTS: CSF CgA was increased in the AD and AD/DLB groups compared with the DLB group (p = 0.0006 between AD and DLB, p = 0.0013 between AD/DLB and DLB). No significant difference in CgA concentration was found between DLB and CS. ROC curve analysis showed an area under the curve of 0.791 between AD and DLB. CgA concentrations were correlated with t-Tau and P-Tau regardless of the pathology (for Tau: p = 0.022 for AD; p < 0.0001 for DLB; p = 0.004 for AD/DLB; for P-Tau: p = 0.032 for AD; p < 0.0001 for DLB; p = 0.0009 for AD/DLB). Aß42 was positively correlated with CgA in the DLB group but not in the AD and AD/DLB groups (for DLB: p < 0.0001; for AD: p = 0.57; for AD/DLB: p = 0.58). CONCLUSIONS: CSF CgA concentrations are increased in AD but not in DLB and correlate with P-Tau and Tau whatever the disease. These results suggest a link between tauopathy/neurodegeneration and CgA.
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Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Doença de Alzheimer/diagnóstico , Doença por Corpos de Lewy/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Cromogranina A , Proteínas tau , Fragmentos de Peptídeos , Biomarcadores/líquido cefalorraquidianoRESUMO
OBJECTIVES: To evaluate differences in presentation and outcome of giant cell arteritis (GCA) patients with and without large vessel vasculitis (LVV) and according to the extent and severity of LVV. METHODS: Consecutive patients diagnosed with GCA between 2003 and 2020 who have had FDG PET imaging at diagnosis ≤3 days after initiation of glucocorticoids and followed for ≥12 months at the University Hospitals Leuven (Belgium), were included retrospectively. PET scans were visually scored (0-3) in 7 vascular areas and a total vascular score (TVS) was calculated. LVV was defined as FDG uptake ≥2 in any large vessel. RESULTS: We included 238 GCA patients, of which 169 (71%) had LVV. LVV patients were younger (69 vs 74 years, p< 0.001) and more frequently female (72% vs 49%, p= 0.001). In patients without PMR symptoms, the presence of LVV was associated with relapse (aOR 3.05 [95%CI 1.32-7.43], p= 0.011) and with a lower probability of stopping glucocorticoids (aHR 0.59 [95%CI 0.37-0.94], p= 0.025). However, in those with PMR symptoms, there was no difference in relapse risk (aOR 1.20 [95%CI 0.53-2.66], p= 0.657) and in the probability of stopping glucocorticoids (aHR 1.25 [95%CI 0.75-2.09], p= 0.394) between patients with and without LVV. A higher TVS was associated with an increased risk of relapse (aOR 1.09 [95%CI 1.04-1.15], p= 0.001] in patients without PMR symptoms, but not in those with PMR symptoms (aOR 1.01 [95%CI 0.96-1.07], p= 0.693). CONCLUSION: LVV is a risk factor for relapse in GCA patients without PMR symptoms with a higher relapse risk in those with higher TVS.
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BACKGROUND AND OBJECTIVES: This study aimed to assess the effectiveness of Comprehensive Geriatric Assessment (CGA) in customizing care for elderly cancer patients, specifically focusing on colorectal cancer. The research compared treatment strategies and outcomes in older adults considered for surgery before and after the initiation of a Geriatric Oncology Service (GOS). METHODS: Conducting a comparative study, two cohorts of consecutive colorectal cancer patients aged 75 or older were examined: the control group (n = 156) and the GOS group (n = 158). Upon the treating surgeon's GOS consultation request, a geriatrician and an oncologist performed CGA, guiding treatment decisions and perioperative interventions. Postoperative complications were compared using propensity score matching (PSM). RESULTS: In the GOS group, 91% (n = 116) underwent CGA consultations, influencing decisions to forego surgery in 12 patients. After PSM for surgical cases (controls n = 146, GOS n = 146), each group comprised 128 patients. Perioperative physical therapy and pharmacist referrals were more frequent in the GOS group. The GOS group exhibited a significantly lower incidence of postoperative complications (22%) compared to the control group (33%) (p = 0.0496). CONCLUSION: Patients undergoing colorectal surgery post-GOS implementation experienced a notable reduction in postoperative complications, highlighting the positive impact of personalized geriatric assessment on surgical outcomes in the elderly.
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Neoplasias Colorretais , Avaliação Geriátrica , Complicações Pós-Operatórias , Humanos , Neoplasias Colorretais/cirurgia , Feminino , Masculino , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso de 80 Anos ou mais , Pontuação de Propensão , Estudos de Casos e Controles , SeguimentosRESUMO
PURPOSE: The Multidimensional Prognostic Index (MPI) is a tool capable of holistically frame older patients in different settings and affected by different pathologies, establishing a risk of adverse events. Among them, type 2 diabetes mellitus (T2DM), a common metabolic disease in the elderly, is responsible for complications and deaths. Few previous works have focused specifically on MPI and DM, and none have followed up the patients for more than 3 years. The aim of the present study is to analyze MPI accuracy in predicting mortality in a cohort of T2DM patients followed-up for 13 years. METHODS: The enrolled subjects were evaluated with MPI, identifying three levels of risk: MPI1 (low risk, 0.0-0.33), MPI2 (moderate risk, 0.34-0.66), and MPI3 (severe risk, 0.67-1.0), and with glycated hemoglobin, and years since T2DM diagnosis. RESULTS: One hundred and seven patients met the inclusion criteria. MPI3 was excluded by further analysis since it was made up of only three patients. Overall, cognitive performances, autonomies in daily living, nutritional status, risk of pressure injuries, comorbidities, and taken drugs were better (p ≤ 0.0077) in MPI1 than MPI2; moreover, the story of T2DM was shorter (p = 0.0026). Cox model showed an overall 13-year survival of 51.9%, and survival rates were significantly smaller in MPI2 (HR: 4.71, p = 0.0007). Finally, increased age (HR: 1.15), poorer cognitive abilities (HR: 1.26), vascular (HR: 2.15), and kidney (HR: 2.17) diseases were independently associated with death. CONCLUSION: Our results prove that MPI predicts short-, mid-, and even long-term mortality in T2DM patients, whose death seems to be related to age and cognitive status, and even more to vascular and kidney diseases.
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Diabetes Mellitus Tipo 2 , Humanos , Idoso , Prognóstico , Diabetes Mellitus Tipo 2/complicações , Seguimentos , Fatores de Risco , Estado NutricionalRESUMO
BACKGROUND: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome. However, the actual use of assessment instruments in routine geriatric clinical practice and its consistency with the guideline and the current state of literature has not been investigated to date. METHODS: An online survey was developed by an expert group of geriatricians and sent to all licenced geriatricians (n = 569) within Germany. The survey included the following geriatric syndromes: motor function and self-help capability, cognition, depression, pain, dysphagia and nutrition, social status and comorbidity, pressure ulcers, language and speech, delirium, and frailty. Respondents were asked to report which geriatric assessment instruments are used to assess the respective syndromes. RESULTS: A total of 122 clinicians participated in the survey (response rate: 21%); after data cleaning, 76 data sets remained for analysis. All participants regularly used assessment instruments in the following categories: motor function, self-help capability, cognition, depression, and pain. The most frequently used instruments in these categories were the Timed Up and Go (TUG), the Barthel Index (BI), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Visual Analogue Scale (VAS). Limited or heterogenous assessments are used in the following categories: delirium, frailty and social status. CONCLUSIONS: Our results show that the assessment of motor function, self-help capability, cognition, depression, pain, and dysphagia and nutrition is consistent with the recommendations of the S1 guideline for level 2 CGA. Instruments recommended for more frequent use include the Short Physical Performance Battery (SPPB), the Montreal Cognitive Assessment (MoCA), and the WHO-5 (depression). There is a particular need for standardized assessment of delirium, frailty and social status. The harmonization of assessment instruments throughout geriatric departments shall enable more effective treatment and prevention of age-related diseases and syndromes.
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Transtornos de Deglutição , Delírio , Fragilidade , Humanos , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/terapia , Avaliação Geriátrica/métodos , Dor , Inquéritos e QuestionáriosRESUMO
Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively. This review is a summary of current information about CGA, including its natural sources, biosynthesis, metabolism, toxicology, role in combatting chemoresistance, and protective effects against chemotherapy-induced toxicity. It also emphasizes the potential of CGA as a pharmacological adjuvant in cancer treatment with drugs such as 5-fluorouracil, cisplatin, oxaliplatin, doxorubicin, regorafenib, and radiotherapy. By analyzing more than 140 papers from PubMed, Google Scholar, and SciFinder, we hope to find the therapeutic potential of CGA in improving cancer therapy.
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Ácido Clorogênico , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
Improper use of acetaminophen (APAP) will induce acute liver failure. This study is designed to investigate whether early growth response-1 (EGR1) participated in the promotion on liver repair and regeneration after APAP-induced hepatotoxicity provided by natural compound chlorogenic acid (CGA). APAP induced the nuclear accumulation of EGR1 in hepatocytes regulated by extracellular-regulated protein kinase (ERK)1/2. In Egr1 knockout (KO) mice, the liver damage caused by APAP (300 mg/kg) was more severe than in wild-type (WT) mice. Results of chromatin immunoprecipitation and sequencing (ChIP-Seq) manifested that EGR1 could bind to the promoter region in Becn1, Ccnd1, and Sqstm1 (p62) or the catalytic/modify subunit of glutamate-cysteine ligase (Gclc/Gclm). Autophagy formation and APAP-cysteine adduct (APAP-CYS) clearance were decreased in Egr1 KO mice administered with APAP. The EGR1 deletion reduced hepatic cyclin D1 expression at 6, 12, or 18 h post APAP administration. Meanwhile, the EGR1 deletion also decreased hepatic p62, Gclc and Gclm expression, GCL enzymatic activity, and glutathione (GSH) content and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) activation and thus aggravated oxidative liver injury induced by APAP. CGA increased EGR1 nuclear accumulation; enhanced hepatic Ccnd1, p62, Gclc, and Gclm expression; and accelerated the liver regeneration and repair in APAP-intoxicated mice. In conclusion, EGR1 deficiency aggravated liver injury and obviously delayed liver regeneration post APAP-induced hepatotoxicity through inhibiting autophagy, enhancing liver oxidative injury, and retarding cell cycle progression, but CGA promoted the liver regeneration and repair in APAP-intoxicated mice via inducing EGR1 transcriptional activation.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Animais , Camundongos , Acetaminofen , Ácido Clorogênico/farmacologia , Ácido Clorogênico/metabolismo , Regeneração Hepática , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/patologia , Glutationa/metabolismo , Hiperplasia/metabolismo , Hiperplasia/patologia , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: the identification and management of frailty occurs mostly in primary care. Several different models of care exist. This study aimed to assess the impact of a new General Practitioner (GP)-led modified Comprehensive Geriatric Assessment (CGA) on service delivery, healthcare utilisation and patient outcomes. METHOD: patients with moderate-severe frailty (electronic Frailty Index score > 0.24) in Newbattle Medical Practice, Scotland, were eligible for a novel intervention (MidMed) in which an additional GP performed a modified CGA and was directly accessible for appointments. The recruits to the intervention (MidMed) group were compared with those waiting to be enrolled (non-MidMed). Outcomes included unscheduled hospital admissions, primary care consultations, continuity of care (Usual Provider of Care (UPC) index), outpatient attendances and mortality. Adjusted rate ratios (aRR), for MidMed compared to non-MidMed, were estimated using regression models adjusting for demographics and healthcare utilisation histories. RESULTS: 510 patients were included: 290 MidMed (mean(SD) age 80.1(7.6)years; 59.6% female) and 220 non-MidMed (75.4(8.6)years; 57.7% female). Median follow-up was 396 days. aRR(95%CI) was 0.46(0.30-0.71) for >1 admission, 0.62(0.41-0.95) >1 Emergency Department (ED) attendance and 1.52(1.30-1.75) for use of primary care, with no difference in outpatient appointments or mortality. Continuity of care was better for the MidMed group (MidMed UPC 0.77(SD 0.19), non-MidMed 0.41(0.18), P < 0.001). CONCLUSION: this GP-led service for frail patients was associated with lower risk of hospital readmission/ED reattendance, greater use of primary care and improved continuity of care. More detailed evaluation of novel primary care frailty services, over longer time-periods, including robust randomised controlled trials, are needed.
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Fragilidade , Clínicos Gerais , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Fragilidade/diagnóstico , Fragilidade/terapia , Avaliação Geriátrica , Hospitalização , Readmissão do Paciente , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: Hyponatremia presents with symptoms considered age-associated in the elderly. We assess the change in Comprehensive Geriatric Assessment (CGA) parameters after hyponatremia improvement in hospitalized geriatric patients. METHODS: We took 100 hyponatremic and same number of eunatremic geriatric patients (> 60 years) who were comorbidity, presenting-complaints, and age-matched. Four CGA parameters were utilized, the new Hindi Mental State Examination (HMSE), Barthel's index of activities of daily living (ADL), Timed up and go Test (TUG), and handgrip strength by hand dynamometer (HG). We analyzed these at admission and discharge, and their relationship with change in sodium levels. RESULTS: Average age was 68.1 ± 5.8 years, with males constituting 75%. The CGA parameters demonstrated worse values amongst the hyponatremia than the normonatremia group. Severe hyponatremia group showed worse CGA scores in comparison with moderate and mild. With improvement in sodium level, the improvements in ADL, TUG, and HMSE scores were greater in the hyponatremia group (8.8 ± 10.1, 2.2 ± 2.5, and 1.7 ± 2.3 respectively) in comparison to the normonatremia reference group (4.7 ± 9.0, 1 ± 2.0, and 0.7 ± 1.3 respectively, P < 0.05). CONCLUSION: Our study is the first utilizing HMSE to assess change in cognitive ability with improvement in serum sodium levels in the Indian elderly. Hyponatremic patients show worse baseline CGA parameters, and hyponatremia severity correlates with worse motor and cognitive function. Improvement in the serum sodium level improves the CGA parameters. Correction of hyponatremia in the geriatric age group significantly impacts life quality.
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Hiponatremia , Masculino , Idoso , Humanos , Hiponatremia/diagnóstico , Hiponatremia/epidemiologia , Hiponatremia/terapia , Atividades Cotidianas , Avaliação Geriátrica , Força da Mão , Equilíbrio Postural , Estudos de Tempo e Movimento , SódioRESUMO
In recent years, neural networks based on attention mechanisms have seen increasingly use in speech recognition, separation, and enhancement, as well as other fields. In particular, the convolution-augmented transformer has performed well, as it can combine the advantages of convolution and self-attention. Recently, the gated attention unit (GAU) was proposed. Compared with traditional multi-head self-attention, approaches with GAU are effective and computationally efficient. In this CGA-MGAN: MetricGAN based on Convolution-augmented Gated Attention for Speech Enhancement, we propose a network for speech enhancement called CGA-MGAN, a kind of MetricGAN based on convolution-augmented gated attention. CGA-MGAN captures local and global correlations in speech signals at the same time by fusing convolution and gated attention units. Experiments on Voice Bank + DEMAND show that our proposed CGA-MGAN model achieves excellent performance (3.47 PESQ, 0.96 STOI, and 11.09 dB SSNR) with a relatively small model size (1.14 M).
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Background: Falls in older people have a significant impact on public health. The scientific literature has provided evidence about the necessity for older adults to be physically active, since it reduces the incidence of falls, several diseases, and deaths, and can even slow down some effects of aging. The primary aim of our study is to identify if physical performances and risk of falling are related to 1-, 2-, 3-, 4-, and 5-year mortality. Its secondary aim is to establish if people with both severely impaired physical performance and a high risk of falling also present impairment in other geriatric domains. Methods: In this prospective study, we enrolled subjects aged 65 years or more, subjected them to comprehensive assessment (including assessment of risk of falling, physical capacities, comorbidities, autonomies in daily living, cognitive abilities, mood, and nutritional status), and followed them for 5 years. Results: We included 384 subjects, 280 of whom were women (72.7%), with a median age of 81 years. Our results showed that physical performances and risk of falling are highly correlated to each other (rho = 0.828). After divided the sample into three groups (people without augmented risk of falling and able to perform adequate physical activity; people with moderate risk of falling and/or disability; people with severe risk of falling and/or disability), we found that the more severe the disability and risk of falling were, the more compromised the other geriatric domains were. Moreover, the survival probability progressively increased following the same trend, amounting to only 41% in severely compromised people, 51.1% in moderately compromised people, and 62.8% in people without physical compromise nor an augmented falling risk (p = 0.0124). Conclusions: Poor physical performance combined with a high risk of falling, correlated with each other, are associated with higher mortality and impairment in multiple domains in older adults.
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Acidentes por Quedas , Vida Independente , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Prospectivos , Exercício Físico , Desempenho Físico FuncionalRESUMO
CGA47-66 (Chromofungin, CHR), is a peptide derived from the N-terminus of chromogranin A (CgA), has been proven to inhibit the lipopolysaccharide (LPS)-induced brain injury. However, the underlying mechanism is still unknown. We found that CGA47-66 exerted a protective effect on cognitive impairment by inhibiting the destruction of the blood-brain barrier (BBB) in the LPS-induced sepsis mice model. In addition, the hCMEC/D3 cell line was used to establish an in vitro BBB model. Under LPS stimulation, CGA47-66 could significantly alleviate the hyperpermeability of the BBB, the destruction of tight junction proteins, and the rearrangement of F-actin. To investigate the underlying mechanism, we used LY294002, a PI3K inhibitor, which partially reduced the protective effect of CGA47-66 on the integrity of BBB. Indicating that the PI3K/AKT pathway plays a vital role in the brain-protective function of CGA47-66, which might be a potential therapeutic target for septic brain injury.
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Barreira Hematoencefálica , Lesões Encefálicas , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Lesões Encefálicas/prevenção & controle , Cromogranina A/metabolismo , Cromogranina A/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
An increasing number of older patients are having surgical treatments. Similar to older patients admitted to intensive care, they present with additional problems including multimorbidity, frailty, and cognitive impairment. In both intensive care and surgical settings, comprehensive assessment can inform targeted interventions and shared decision-making. We explore the challenges faced by older patients, and by the clinicians treating them.
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Fragilidade , Avaliação Geriátrica , Humanos , Idoso , Multimorbidade , Cuidados Críticos , Tomada de Decisão CompartilhadaRESUMO
BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.
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Fragilidade , Mieloma Múltiplo , Idoso , Idoso de 80 Anos ou mais , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Mieloma Múltiplo/diagnóstico , Estudos ProspectivosRESUMO
Worldwide, falls and accompanying injuries are increasingly common, making their prevention and management a critical global challenge. The wealth of evidence to support interventions to prevent falls has recently (2022) been distilled in the first World Falls Guideline for Prevention and Management for Older Adults. The core of falls prevention includes (i) risk assessment and stratification; (ii) general recommendations on optimising physical function and mobility for all and (iii) offering a holistic, multidomain intervention to older adults at high risk of falls, in which the older adult's priorities, beliefs and resources are carefully considered. In recent decades, sustainable and adequately resourced falls prevention has proved challenging, although evidence suggests that suboptimal implementation of falls prevention is ineffective. Future research should focus on understanding the most successful approaches for implementation. To further optimise falls prevention, recent developments include technological innovation to identify and prevent falls, including exergaming. Further work is warranted to understand how to best incorporate the concepts of frailty and sarcopenia in falls prevention and management. This themed collection includes key articles in the field of falls prevention, covering several topics including risk factors, effective interventions, older adult's views, implementation issues and future perspectives.
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Acidentes por Quedas , Humanos , Idoso , Acidentes por Quedas/prevenção & controle , Medição de Risco , Fatores de RiscoRESUMO
Antimicrobial peptides (AMPs) are conventional antibiotic alternatives due to their broad-spectrum antimicrobial activities and special mechanisms of action against pathogens. The antifungal peptide CGA-N12 was originally derived from human chromogranin A (CGA) and consists of the 65th to 76th amino acids of the CGA N-terminal region. In the present study, we found that CGA-N12 had fungicidal activity and exhibited time-dependent inhibition activity against Candida tropicalis. CGA-N12 entered the cells to exert its antagonist activity. The internalization of CGA-N12 was energy-dependent and accompanied by actin cytoskeleton-, clathrin-, sulfate proteoglycan-, endosome-, and lipid-depleting agent-mediated endocytosis. Moreover, the CGA-N12 internalization pathway was related to the peptide concentration. The effects of CGA-N12 on the cell membrane were investigated. CGA-N12 at a low concentration less than 4 × MIC100 did not destroy the cell membrane. While with increasing concentration, the damage to the cell membrane caused by CGA-N12 became more serious. At concentrations greater than 4 × MIC100, CGA-N12 destroyed the cell membrane integrity. Therefore, the membrane activity of CGA-N12 is concentration dependant.
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Antifúngicos/farmacologia , Candida tropicalis/efeitos dos fármacos , Membrana Celular/metabolismo , Cromogranina A/metabolismo , Endocitose , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Transporte Biológico , Cálcio/metabolismo , Candida tropicalis/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , HumanosRESUMO
BACKGROUND: Fear of falling (FOF) is a common and major health concern in older adults. The consequences of FOF include reduced physical performance, social activity, and health-related quality of life. Ramsay Hunt syndrome (RHS) is a herpes zoster-related facial nerve dysfunction accompanied by an erythematous vesicular rash on the ear or mouth that may complicate ipsilateral facial paralysis and otalgia, vertigo, tinnitus, hearing loss, and meningoencephalitis. However, repeated falls and subsequent FOF due to RHS have not been reported in older adults. CASE PRESENTATION: A 65-year-old woman diagnosed with RHS experienced repeated falls during hospital admission and after discharge. Despite recovery of balance and no subsequent falls, the patient presented with persistent FOF at the geriatric outpatient follow-up visit 1 year after the RHS episode. The fear sensation impaired the patient's instrumental daily activities and was confirmed by documentation of serial comprehensive geriatric assessments, especially the Timed Up and Go test scores. CONCLUSIONS: RHS may cause repeated falls and FOF, leading to impairment in daily activities and psychosocial function in older adults. Therefore, clinicians should be mindful of falls and FOF when caring for older patients with RHS and should develop multidimensional strategies for fall prevention and FOF.
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Acidentes por Quedas , Herpes Zoster da Orelha Externa , Feminino , Humanos , Idoso , Acidentes por Quedas/prevenção & controle , Herpes Zoster da Orelha Externa/complicações , Herpes Zoster da Orelha Externa/diagnóstico , Medo/psicologia , Equilíbrio Postural , Qualidade de Vida , Estudos de Tempo e MovimentoRESUMO
BACKGROUND: Orthostatic Hypotension (OH) and malnutrition, are common health problems in elderly hypertensive patients. This study aimed to analyze the relationship between malnutrition and OH in elderly hypertensive patients. METHODS: This is a cross-sectional single-center study. All participants underwent a Comprehensive Geriatric Assessment (CGA), in which malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) criteria based on four different methods of diagnosing muscle mass loss. Furthermore, the accuracy of these methods was verified by Receiver Operating Characteristic (ROC) analysis. Univariate and multivariate logistic regression analyses were used to identify risk factors for OH in elderly hypertensive patients. RESULTS: For GLIM criteria, when Fat-Free Mass Index (FFMI) was the gold standard for muscle mass loss, the Area Under ROC Curve (AUC) values for Upper Arm Circumference (UAC), Calf Circumference (CC), and Hand Grip Strength (HGS) were 0.784, 0.805, and 0.832, with moderate accuracy in diagnosing malnutrition. Multivariate analysis showed that females, Diabetes Mellitus (DM), diuretics, and malnutrition diagnosed by GLIM-UAC were risk factors for OH in elderly hypertensive patients. CONCLUSION: Prompt detection of malnutrition in the elderly and attention to changes in UAC may be critical. Similarly, we should strengthen medication and disease management in elderly hypertensive patients.
Assuntos
Hipotensão Ortostática , Desnutrição , Feminino , Humanos , Idoso , Hipotensão Ortostática/diagnóstico , Hipotensão Ortostática/epidemiologia , Estado Nutricional , Força da Mão , Liderança , Estudos Transversais , Desnutrição/complicações , Desnutrição/diagnóstico , Desnutrição/epidemiologiaRESUMO
BACKGROUND: Due to demographic change, the number of older people in Germany and worldwide will continue to rise in the coming decades. As a result, the number of elderly and frail patients undergoing total hip and knee arthroplasty is projected to increase significantly in the coming years. In order to reduce risk of complications and improve postoperative outcome, it can be beneficial to optimally prepare geriatric patients before orthopaedic surgery and to provide perioperative care by a multiprofessional orthogeriatric team. The aim of this comprehensive interventional study is to assess wether multimorbid patients can benefit from the new care model of special orthopaedic geriatrics (SOG) in elective total hip and knee arthroplasty. METHODS: The SOG study is a registered, monocentric, prospective, randomized controlled trial (RCT) funded by the German Federal Joint Committee (GBA). This parallel group RCT with a total of 310 patients is intended to investigate the specially developed multimodal care model for orthogeriatric patients with total hip and knee arthroplasty (intervention group), which already begins preoperatively, in comparison to the usual orthopaedic care without orthogeriatric co-management (control group). Patients ≥70 years of age with multimorbidity or generally patients ≥80 years of age due to increased vulnerability with indication for elective primary total hip and knee arthroplasty can be included in the study. Exclusion criteria are age < 70 years, previous bony surgery or tumor in the area of the joint to be treated, infection and increased need for care (care level ≥ 4). The primary outcome is mobility measured by the Short Physical Performance Battery (SPPB). Secondary outcomes are morbidity, mortality, postoperative complications, delirium, cognition, mood, frailty, (instrumental) activities of daily living, malnutrition, pain, polypharmacy, and patient reported outcome measures. Tertiary outcomes are length of hospital stay, readmission rate, reoperation rate, transfusion rate, and time to rehabilitation. The study data will be collected preoperative, postoperative day 1 to 7, 4 to 6 weeks and 3 months after surgery. DISCUSSION: Studies have shown that orthogeriatric co-management models in the treatment of hip fractures lead to significantly reduced morbidity and mortality rates. However, there are hardly any data available on the elective orthopaedic care of geriatric patients, especially in total hip and knee arthroplasty. In contrast to the care of trauma patients, optimal preoperative intervention is usually possible. TRIAL REGISTRATION: German Clinical Trials Register DRKS00024102. Registered on 19 January 2021.