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1.
BMC Med ; 22(1): 212, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38807210

RESUMO

BACKGROUND: To examine the effectiveness and safety of a data sharing and comprehensive management platform for institutionalized older patients. METHODS: We applied information technology-supported integrated health service platform to patients who live at long-term care hospitals (LTCHs) and nursing homes (NHs) with cluster randomized controlled study. We enrolled 555 patients aged 65 or older (461 from 7 LTCHs, 94 from 5 NHs). For the intervention group, a tablet-based platform comprising comprehensive geriatric assessment, disease management, potentially inappropriate medication (PIM) management, rehabilitation program, and screening for adverse events and warning alarms were provided for physicians or nurses. The control group was managed with usual care. Co-primary outcomes were (1) control rate of hypertension and diabetes, (2) medication adjustment (PIM prescription rate, proportion of polypharmacy), and (3) combination of potential quality-of-care problems (composite quality indicator) from the interRAI assessment system which assessed after 3-month of intervention. RESULTS: We screened 1119 patients and included 555 patients (control; 289, intervention; 266) for analysis. Patients allocated to the intervention group had better cognitive function and took less medications and PIMs at baseline. The diabetes control rate (OR = 2.61, 95% CI 1.37-4.99, p = 0.0035), discontinuation of PIM (OR = 4.65, 95% CI 2.41-8.97, p < 0.0001), reduction of medication in patients with polypharmacy (OR = 1.98, 95% CI 1.24-3.16, p = 0.0042), and number of PIMs use (ꞵ = - 0.27, p < 0.0001) improved significantly in the intervention group. There was no significant difference in hypertension control rate (OR = 0.54, 95% CI 0.20-1.43, p = 0.2129), proportion of polypharmacy (OR = 1.40, 95% CI 0.75-2.60, p = 0.2863), and improvement of composite quality indicators (ꞵ = 0.03, p = 0.2094). For secondary outcomes, cognitive and motor function, quality of life, and unplanned hospitalization were not different significantly between groups. CONCLUSIONS: The information technology-supported integrated health service effectively reduced PIM use and controlled diabetes among older patients in LTCH or NH without functional decline or increase of healthcare utilization. TRIAL REGISTRATION: Clinical Research Information Service, KCT0004360. Registered on 21 October 2019.


Assuntos
Prestação Integrada de Cuidados de Saúde , Assistência de Longa Duração , Humanos , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Assistência de Longa Duração/métodos , Tecnologia da Informação , Casas de Saúde , Polimedicação
2.
Dev Comp Immunol ; 154: 105145, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38316233

RESUMO

Spring viremia of carp virus (SVCV) is a globally distributed virus that causes severe clinical symptoms and high mortality in fish belonging to the families Cyprinidae and Siluridae. To protect the host against viral infection, understanding the relatedness between viral susceptibility and antiviral mechanisms must be crucial. Thus, we evaluated the viral suppression efficacy of ribavirin by measuring the transcription levels of viral and immune genes in vitro. The results showed that following ribavirin treatment after SVCV infection (MOI 0.1), ribavirin inhibited SVCV replication in epithelioma papulosum cyprini (EPC) cells and completely inhibited viral gene (G and N) expression at concentrations above 10 µg/mL at 48 h post-infection. Ribavirin does not directly damage SVCV particles but inhibits early viral replication. In the absence of SVCV infection, the immunological dynamics triggered by ribavirin resulted in upregulated pattern recognition receptors and proinflammatory cytokine-related genes (i.e., PI3K, MYD88, IRAK1, RIG-І, MAVS, Mx1, TNF-α, and NF-κB). Furthermore, EPC cells treated with ribavirin following SVCV infection showed upregulation of PI3K, MYD88, IRAK1, RIG-І, TNF-α, and NF-κB genes within 24 h post-SVCV infection, suggesting that ribavirin positively inhibits the SVCV infection in vitro.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Rhabdoviridae , Rhabdoviridae , Humanos , Animais , Ribavirina/uso terapêutico , Ribavirina/farmacologia , Viremia/tratamento farmacológico , NF-kappa B , Fator de Necrose Tumoral alfa , Fator 88 de Diferenciação Mieloide/genética , Rhabdoviridae/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Fosfatidilinositol 3-Quinases
3.
Sci Rep ; 14(1): 1485, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233529

RESUMO

This study developed and validated a risk-scoring model, with a particular emphasis on medication-related factors, to predict emergency department (ED) visits among older Korean adults (aged 65 and older) undergoing anti-neoplastic therapy. Utilizing national claims data, we constructed two cohorts: the development cohort (2016-2018) with 34,642 patients and validation cohort (2019) with 10,902 patients. The model included a comprehensive set of predictors: demographics, cancer type, comorbid conditions, ED visit history, and medication use variables. We employed the least absolute shrinkage and selection operator (LASSO) regression to refine and select the most relevant predictors. Out of 120 predictor variables, 12 were integral to the final model, including seven related to medication use. The model demonstrated acceptable predictive performance in the validation cohort with a C-statistic of 0.76 (95% CI 0.74-0.77), indicating reasonable calibration. This risk-scoring model, after further clinical validation, has the potential to assist healthcare providers in the effective management and care of older patients receiving anti-neoplastic therapy.


Assuntos
Visitas ao Pronto Socorro , Serviço Hospitalar de Emergência , Adulto , Humanos , Idoso , Fatores de Risco
4.
J Med Food ; 26(12): 927-938, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38064431

RESUMO

Cisplatin, a potent and prominent chemotherapeutic drug, has considerable side effects, including nephrotoxicity, which limits its therapeutic application and efficacy. Therefore, the development of agents that protect normal cells while preserving cisplatin's chemotherapeutic properties is of utmost importance. This study aimed to explore the protective effects of Bombyx batryticatus protein-rich extract (BBPE) against cisplatin-induced nephrotoxicity in a cisplatin-treated mouse model and human embryonic kidney (HEK293) cells. Apoptosis was assessed in HEK293 cells to determine the cytoprotective effects of BBPE and its effects on the generation of cisplatin-induced reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) collapse. Although cisplatin induced nephrotoxicity in HEK293 cells, pretreatment with BBPE showed significant protective effects against cisplatin-induced nephrotoxicity by regulating the expression levels of pro- and antiapoptotic proteins. The cytoprotective effects of BBPE were mediated by decreased ROS production and MTP loss in cisplatin-treated HEK293 cells. The in vitro results were confirmed in the cisplatin-treated mouse model. Pretreatment with BBPE protected against cisplatin-induced nephrotoxicity by restoring malondialdehyde, superoxide dismutase, and catalase levels in kidney tissue and blood urea nitrogen and creatinine serum levels. Furthermore, histopathological assessment and terminal dUTP nick end-labeling staining showed that BBPE mitigated cisplatin-induced nephrotoxicity in kidney tissues. Overall, BBPE may act as a potent agent for alleviating cisplatin-induced nephrotoxicity, thereby increasing the safety of cisplatin-based chemotherapy.


Assuntos
Bombyx , Cisplatino , Camundongos , Animais , Humanos , Cisplatino/efeitos adversos , Células HEK293 , Espécies Reativas de Oxigênio/metabolismo , Bombyx/metabolismo , Estresse Oxidativo , Glutationa/metabolismo , Rim , Apoptose
5.
J Med Internet Res ; 25: e42259, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37955965

RESUMO

BACKGROUND: Older adults are at an increased risk of postoperative morbidity. Numerous risk stratification tools exist, but effort and manpower are required. OBJECTIVE: This study aimed to develop a predictive model of postoperative adverse outcomes in older patients following general surgery with an open-source, patient-level prediction from the Observational Health Data Sciences and Informatics for internal and external validation. METHODS: We used the Observational Medical Outcomes Partnership common data model and machine learning algorithms. The primary outcome was a composite of 90-day postoperative all-cause mortality and emergency department visits. Secondary outcomes were postoperative delirium, prolonged postoperative stay (≥75th percentile), and prolonged hospital stay (≥21 days). An 80% versus 20% split of the data from the Seoul National University Bundang Hospital (SNUBH) and Seoul National University Hospital (SNUH) common data model was used for model training and testing versus external validation. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) with a 95% CI. RESULTS: Data from 27,197 (SNUBH) and 32,857 (SNUH) patients were analyzed. Compared to the random forest, Adaboost, and decision tree models, the least absolute shrinkage and selection operator logistic regression model showed good internal discriminative accuracy (internal AUC 0.723, 95% CI 0.701-0.744) and transportability (external AUC 0.703, 95% CI 0.692-0.714) for the primary outcome. The model also possessed good internal and external AUCs for postoperative delirium (internal AUC 0.754, 95% CI 0.713-0.794; external AUC 0.750, 95% CI 0.727-0.772), prolonged postoperative stay (internal AUC 0.813, 95% CI 0.800-0.825; external AUC 0.747, 95% CI 0.741-0.753), and prolonged hospital stay (internal AUC 0.770, 95% CI 0.749-0.792; external AUC 0.707, 95% CI 0.696-0.718). Compared with age or the Charlson comorbidity index, the model showed better prediction performance. CONCLUSIONS: The derived model shall assist clinicians and patients in understanding the individualized risks and benefits of surgery.


Assuntos
Delírio do Despertar , Humanos , Idoso , Prognóstico , Estudos Retrospectivos , Algoritmos , Aprendizado de Máquina
6.
Theranostics ; 13(15): 5247-5265, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908724

RESUMO

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are potent technologies for non-invasive imaging of pharmacological and biochemical processes in both preclinical and advanced clinical research settings. In the field of radiation therapy, boron neutron capture therapy (BNCT) stands out because it harnesses biological mechanisms to precisely target tumor cells while preserving the neighboring healthy tissues. To achieve the most favorable therapeutic outcomes, the delivery of boron-enriched tracers to tumors must be selective and efficient, with a substantial concentration of boron atoms meticulously arranged in and around the tumor cells. Although several BNCT tracers have been developed to facilitate the targeted and efficient delivery of boron to tumors, only a few have been labeled with PET or SPECT radionuclides. Such radiolabeling enables comprehensive in vivo examination, encompassing crucial aspects such as pharmacodynamics, pharmacokinetics, tumor selectivity, and accumulation and retention of the tracer within the tumor. This review provides a comprehensive summary of the essential aspects of BNCT tracers, focusing on their radiolabeling with PET or SPECT radioisotopes. This leads to more effective and targeted treatment approaches which ultimately enhance the quality of patient care with respect to cancer treatment.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias , Humanos , Terapia por Captura de Nêutron de Boro/métodos , Boro , Tomografia por Emissão de Pósitrons/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Compostos de Boro
7.
PLoS One ; 18(3): e0281532, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36920888

RESUMO

Patients with hypertension are at higher risk for dementia than the general population. We sought to understand the relative importance of various risk factors in the development of dementia among patients with hypertension. This population-based cohort study used data from the Korean National Insurance Service database. Using the Cox proportional hazard model, R2 values for each potential risk factor were calculated to test the relative importance of risk factors for the development of dementia. Eligible individuals were adults 40 to 79 years of age with hypertension and without a history of stroke and dementia between 2007 and 2009. A total of 650,476 individuals (mean age, 60 ± 11 years) with hypertension were included in the analyses. During a mean follow-up of 9.5 years (±2.8 years), 57,112 cases of dementia were observed. The three strongest predictors of dementia were age, comorbidity burden (assessed using the Charlson Comorbidity Index), and female sex (R2 values, 0.0504, 0.0023, and 0.0022, respectively). The next strongest risk factors were physical inactivity, smoking, alcohol consumption, and obesity (R2 values, 0.00070, 0.00024, 0.00021, and 0.00020, respectively). Across all age groups, physical inactivity was an important risk factor for dementia occurrence. In summary, controlling and preventing comorbidities are of utmost importance to prevent dementia in patients with hypertension. More efforts should be taken to encourage physical activity among patients with hypertension across all age groups. Furthermore, smoking cessation, avoiding and limiting alcohol consumption, and maintaining an appropriate body weight are urged to prevent dementia.


Assuntos
Demência , Hipertensão , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Fatores de Risco , Hipertensão/complicações , Hipertensão/epidemiologia , Comorbidade , Demência/epidemiologia , Demência/etiologia
8.
Animals (Basel) ; 13(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36899800

RESUMO

Iron flocculation is widely used to concentrate viruses in water, followed by Fe-virus flocculate formation, collection, and elution. In the elution stage, an oxalic or ascorbic acid re-suspension buffer dissolved iron hydroxide. After the concentration of viral hemorrhagic septicemia virus (VHSV) in seawater (1 × 101 to 1 × 105 viral genome copies or plaque-forming unit (PFU)/mL), the recovery yield of the viral genome using quantitative real-time PCR (qRT-PCR) and viral infectivity using the plaque assay were investigated to evaluate the validity of the two re-suspension buffers to concentrate VHSV. The mean viral genome recovery yield with oxalic and ascorbic acid was 71.2 ± 12.3% and 81.4 ± 9.5%, respectively. The mean viral infective recovery yields based on the PFU were significantly different between the two buffers at 23.8 ± 22.7% (oxalic acid) and 4.4 ± 2.7% (ascorbic acid). Notably, although oxalic acid maintains viral infectivity over 60% at a viral concentration above 105 PFU/mL, the infective VHSVs were not sufficiently recovered at a low viral concentration (102 PFU/mL, <10%). To support this result, concentrated VHSV was inoculated in Epithelioma papulosum cyprini (EPC) cells to confirm cell viability, viral gene expression, and extracellular viral titer. All results demonstrated that oxalic acid buffer was superior to ascorbic acid buffer in preserving viral infectivity.

9.
Mol Med Rep ; 27(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36453199

RESUMO

Cisplatin is a prominent chemotherapeutic agent that can induce significant damage to normal cells. Therefore, it is important to develop agents that protect normal cells without influencing the chemotherapeutic effect of cisplatin. The present study was conducted to explore the protective effects of Annona muricata leaf polysaccharides (ALPS) against cisplatin­induced toxicity in macrophages. Apoptosis was assessed in macrophages and lung cancer cells to investigate the cytoprotective effect of ALPS, their effect on the production of cisplatin­induced reactive oxygen species (ROS) and the loss of the mitochondrial transmembrane potential (MTP). Cisplatin, when used alone or in combination with ALPS, showed significant toxicity against A549 and H460 lung cancer cells. However, cisplatin­induced cytotoxicity was suppressed by cotreatment of RAW 264.7 macrophages with ALPS. ALPS significantly inhibited the upregulation of Bax, cytosolic cytochrome c and caspases­3, ­8 and ­9. Moreover, ALPS resulted in the cleavage of PARP and downregulation of Bcl­2 levels in a concentration­dependent manner, which ultimately led to a reduction in the apoptotic and necrotic populations of cisplatin­treated RAW 264.7 macrophages. The suppression of the apoptotic signaling pathways was mediated through the reduction of ROS and MTP loss in cisplatin­treated RAW 264.7 macrophages. In addition, ALPS alleviated cell damage by suppressing the mitochondrial apoptotic pathways in cisplatin­treated bone marrow­derived macrophages. Together, these findings suggested that ALPS may alleviate the toxic side effects of chemotherapeutic agents and act as a potential candidate for use as an effective adjuvant therapy.


Assuntos
Annona , Neoplasias Pulmonares , Cisplatino/farmacologia , Espécies Reativas de Oxigênio , Polissacarídeos/farmacologia , Macrófagos , Folhas de Planta , Mitocôndrias
10.
J Am Med Dir Assoc ; 24(2): 242-249.e7, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36529274

RESUMO

OBJECTIVES: To evaluate the prevalence of medication-related admissions (MRAs) and their association with potentially inappropriate medications (PIMs) used by nursing home residents admitted to the geriatric center of a tertiary hospital. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Older patients admitted from nursing homes to the geriatric center of the Seoul National University Bundang Hospital who had undergone comprehensive geriatric assessment from January 1, 2016, to December 31, 2020. METHODS: MRAs were determined and verified using a previously described MRA adjudication guide. The PIMs in the preadmission medication lists were identified according to each of the following criteria (as well as the combined criteria), the Beers, NORGEP-NH, STOPP/START-NH, and STOPPFrail criteria. Medication use factors associated with MRAs were analyzed using multivariate logistic regression. RESULTS: Among the 304 acute care admissions, 32.2% were MRAs. The main cause of MRAs was acute kidney injury related with use of renin-angiotensin system inhibitors. Approximately 81% of the patients used at least 1 PIM according to the combined criteria. The use of 1 or more PIMs, renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, and benzodiazepines was significantly associated with MRAs. The combined criteria were able to predict MRAs better than the individual criteria. CONCLUSIONS AND IMPLICATIONS: Approximately one-third of acute admissions of nursing home residents may be MRAs. Interventions for the optimal use of medication among nursing home residents are needed.


Assuntos
Prescrição Inadequada , Polimedicação , Humanos , Idoso , Estudos Transversais , Lista de Medicamentos Potencialmente Inapropriados , Casas de Saúde
11.
Fish Shellfish Immunol ; 132: 108456, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36473646

RESUMO

Viral hemorrhagic septicemia virus (VHSV) causes a severe and often lethal infection in olive flounder (Paralichthys olivaceus) in Korea, resulting in mass mortality and substantial economic loss. As a potential prevention strategy for infectious viral diseases, this study aimed to evaluate the antiviral activity of three compounds (arctigenin [ARG], ribavirin [RBV], and ivermectin [IVM]) against VHSV infection in vitro and in vivo. In epithelioma papulosum cyprini cells, the expression of both VHSV glycoprotein (G) and nucleoprotein (N) genes were significantly suppressed by the three compounds in a dose-dependent manner (P < 0.05). Also, cell morphology and viability were maintained at the following concentrations: ARG 1.5 mg/L, RBV 2.5 mg/L, and IVM 10 mg/L. The fish that were treated with RBV (8.33 mg/kg) and IVM (0.25 mg/kg) before VHSV infection and those treated with IVM (0.25 mg/kg) after VHSV infection showed significant improvements in the survival rate, a reduction in the viral shedding rate, and downregulation of viral gene expression compared to those seen in fish with naïve VHSV infections. Furthermore, among the innate immune genes studied, persistent expression of Mx and upregulation of tumor necrosis factor-α gene expression in VHSV-infected fish treated with RBV and IVM revealed that these compounds might induce an immunostimulatory effect as one of their antiviral activities. Overall, this study supports the use of RBV and IVM as antiviral agents to control VHSV infections in olive flounder.


Assuntos
Doenças dos Peixes , Linguado , Septicemia Hemorrágica Viral , Novirhabdovirus , Animais , Ribavirina/farmacologia , Antivirais/farmacologia , Ivermectina/farmacologia , Novirhabdovirus/fisiologia
12.
Arch Gerontol Geriatr ; 104: 104831, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36279806

RESUMO

BACKGROUND/OBJECTIVES: Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process to evaluate medical, psychosocial, and functional capability. It is useful to develop a coordinated and integrated plan for frail older patients. This study aimed to examine the current scope of CGA based multidisciplinary team interventions in acute care setting to improve the health outcomes for older adults. METHODS: We searched electronic databases: PubMed, Ovid, PsychINFO, Scopus, RISS and KoreaMed from 2011 to 2021. The selected articles were extracted by three reviewers and cross checked by the fourth reviewer to resolve any conflicts. Data were synthesized and analyzed descriptively and thematically. Articles are nested three themes: inpatient (IN), emergency room (ER) and oncology patient (ONCO). RESULTS: Of the 1830 articles that were screened, 710 were potentially eligible. Finally, 26 articles were selected and categorized as IN (n=8), ER (n=7) and ONCO (n=11). Geriatricians and nurses participated in most of the multidisciplinary teams followed by other health professionals. The most effective primary outcomes were focused and retrieved across five domains, screening, prevention, treatment, quality of care, and rehabilitation. The subdomains are problem lists which is common and problematic among hospitalized older patients and retrieved from the most commonly used multidisciplinary interventions according to each domain. CONCLUSION: CGA based multidimensional intervention (MDI) are likely to be an effective in care of older adults. There is remarkable paradigm shift required to improve better health outcomes for hospitalized older adults. It also suggests that there is a need to design the CGA based MDI to build a standardized protocol for older adults to maintain functional capacity and increase likelihood of living in their own home.


Assuntos
Avaliação Geriátrica , Hospitalização , Humanos , Idoso , Avaliação Geriátrica/métodos , Geriatras , Equipe de Assistência ao Paciente
13.
BMJ Open ; 12(8): e060913, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914913

RESUMO

INTRODUCTION: There is an increased demand for services for hospitalised older patients with acute medical conditions due to rapidly ageing population. The COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS) study will test the effectiveness of comprehensive geriatric assessment (CGA) and multidisciplinary intervention by comparing it with conventional care among acute hospitalised older adults in Korea. METHODS AND ANALYSIS: A multicentre trial within a cohort comprising three substudies (randomised controlled trials) will be conducted. The intervention includes CGA and CGA-based multidisciplinary interventions by physicians (geriatricians, oncologists), nurses, nutritionists and pharmacists. The multidisciplinary intervention includes nutritional support, medication review and adjustment, rehabilitation, early discharge planning and prevention of geriatric syndromes (falls, delirium, pressure sore and urinary retention). The analysis will be based on an intention-to-treat principle. The primary outcome is living at home 3 months after discharge. In addition to assessing the economic effects of the intervention, a cost-utility analysis will be conducted. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the ethics committees of Seoul National University Bundang Hospital and each study site. The study findings will be published in peer-reviewed journals. Subgroup and further in-depth analyses will subsequently be published. TRIAL REGISTRATION NUMBER: KCT0006270.


Assuntos
Avaliação Geriátrica , Geriatras , Idoso , Estudos de Coortes , Avaliação Geriátrica/métodos , Humanos , Estudos Multicêntricos como Assunto , Equipe de Assistência ao Paciente , Alta do Paciente , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Pharmaceutics ; 14(7)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35890234

RESUMO

Immuno-positron emission tomography (PET) has great potential to evaluate the target expression level and therapeutic response for targeted cancer therapy. Immuno-PET imaging with pertuzumab, due to specific recognition in different binding sites of HER2, could be useful for the determination of the therapeutic efficacy of HER2-targeted therapy, trastuzumab, and heat shock protein 90 (HSP90) inhibitor, in HER2-expressing breast cancer. The aim of this study is to evaluate the feasibility of monitoring therapeutic response with 89Zr-DFO-pertuzumab for the treatment of HER2-targeted therapeutics, trastuzumab, or the HSP90 inhibitor 17-DMAG, in trastuzumab-resistant JIMT-1 breast cancer models. We prepared an immuno-PET imaging agent using desferoxamine (DFO)-pertuzumab labeled with 89Zr and performed the biodistribution and PET imaging in breast cancer xenograft models for monitoring therapeutic response to HER2-targeted therapy. 89Zr-DFO-pertuzumab was successfully prepared and showed specific binding to HER2 in vitro and clearly visualized HER2 expressing JIMT-1 tumors. 89Zr-DFO-pertuzumab had prominent tumor uptake in HER2 expressing JIMT-1 tumors. JIMT-1 tumors showed trastuzumab-resistant and HSP90 inhibitor sensitive characterization. In immuno-PET imaging, isotype antibody-treated JIMT-1 tumors had similar uptake in trastuzumab-treated JIMT-1 tumors, but 17-DMAG-treated JIMT-1 tumors showed greatly reduced uptake compared to vehicle-treated tumors. Additionally, HER2 downregulation evaluated by immuno-PET imaging was verified by western blot analysis and immunofluorescence staining which resulted in a significant reduction in the tumor's HER2 level in 17-DMAG-treated JIMT-1 tumors. 89Zr-DFO-pertuzumab immuno-PET may be clinically translated to select pertinent patients for HER2-targeted therapy and to monitor the therapeutic response in HER2-positive cancer patients under various HER2-targeted therapeutics treatments.

15.
Blood Res ; 57(S1): 1-5, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35483918

RESUMO

The incidence of hematologic malignancy increases with age; thus, the number of older patients who require intensive chemotherapy is expected to increase with the aging population. In Korea, 61.8%, 59.3%, 47.0%, and 46.7% of newly diagnosed cases of multiple myeloma, myelodysplastic syndrome, myeloproliferative disorder, and non-Hodgkin lymphoma, respectively, occurred in patients aged >65 years in 2018. Health status among older patients, defined by frailty, age-related syndrome of physiological decline and increased vulnerability, is associated with adverse health outcomes. Health status is highly heterogeneous among older patients, and treatment outcomes vary according to frailty and physiologic age rather than chronologic age. Comprehensive geriatric assessment (CGA) is a multidimensional and multidisciplinary diagnostic and treatment process that identifies multiple domains, including functional status, cognition, comorbidities, medications, socioeconomic status, and nutritional status, to develop a coordinated plan to improve treatment-related outcomes and quality of life. Frailty can be assessed with CGA findings, and CGA is considered the "gold standard of care" for frail, older patients. Through CGA, unidentified problems can be assessed, and pre-emptive and non-oncologic interventions can be delivered. CGA is an objective and reliable tool for predicting further treatment-related complications and identifying patients for whom intensive chemotherapy with curative intent is appropriate. CGA should be considered a routine practice before starting treatment planning in older patients diagnosed with hematologic malignancies who require intensive chemotherapy. Further study is needed to allocate individualized treatment plans or multidisciplinary geriatric interventions according to CGA results.

16.
BMC Geriatr ; 22(1): 367, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477358

RESUMO

BACKGROUND: The recently developed Screening Tool of Older Persons' Prescriptions in Frail adults with a limited life expectancy (STOPPFrail) criteria can be helpful for screening medications (PIMs), but it is yet to be widely used in clinical practice. Herein, we aimed to investigate the prevalence of PIMs based on the STOPPFrail criteria (STOPPFrail-PIM) among frail older adults with limited life expectancy admitted to the geriatric center. METHODS: This was a retrospective cross-sectional study conducted in the geriatric center at an academic tertiary care hospital in Korea. We evaluated frail older adults with limited life expectancy who received comprehensive geriatric assessment (CGA) admitted between 1 January, 2019 and 30 June, 2020. Frail older adults with limited life expectancy were identified by geriatricians with retrospective records and the prevalence of STOPPFrail-PIMs was analysed by trained pharmacists. Descriptive analysis, t-test, and chi-square test were conducted using IBM SPSS software version 25.0. RESULTS: Among 504 older adults who underwent CGA after admission, 171 frail older adults with limited life expectancy were identified by geriatricians and included in the study. An average of 11.3 ± 4.7 medications were administered regularly to each patient before admission. Overall, 97.1% (166/171) had at least one STOPPFrail-PIM, and the mean number of STOPPFrail-PIM was 4.2 ± 2.8. Drugs without clear clinical indication (A2) were the most frequent pre-admission STOPPFrail-PIM, followed by lipid-lowering therapies (B1) and neuroleptic antipsychotics (D1). The number of STOPPFrail-PIM was significantly lower at discharge than that at admission, with the decrease being the highest for A2 at 94.7%. CONCLUSIONS: Most frail older adults with limited life expectancy had at least one STOPPFrail-PIM at admission, and the rate of STOPPFrail-PIM decreased significantly at discharge after the geriatric multidisciplinary team care. Further studies are needed to investigate the association between the use of STOPPFrail-PIM and adverse consequences in frail older adults.


Assuntos
Idoso Fragilizado , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Prescrição Inadequada/prevenção & controle , Expectativa de Vida , Prevalência , Estudos Retrospectivos
17.
Korean J Intern Med ; 37(2): 468-477, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35176208

RESUMO

BACKGROUND/AIMS: Drugs with anticholinergic properties (DAPs) are associated with adverse health outcomes in older patients. The objective of this study was to evaluate the factors that determine the prescribing of more DAPs in long-term care hospitals (LTCHs) in Korea. In addition, the current patterns of DAP prescription were explored using a novel platform, which can collect data from LTCHs. METHODS: This was a Health-RESPECT (integrated caRE Systems for elderly PatiEnts using iCT) sub-study, which is a pragmatic, cluster-randomized, controlled trial. The Health-RESPECT platform was used to collect prescribed medication data of 466 patients (aged ≥ 65 years) from seven LTCHs. DAPs were identified using the Korean Anticholinergic Burden Scale (KABS). Physical frailty, cognitive function, functional status, and quality of life were evaluated. RESULTS: Among 466 LTCH patients, 88.8% (n = 414) were prescribed DAPs, and the prevalence of high KABS (≥ 3) was 70.4% (n = 328). The drugs that contributed most to the total KABS were quetiapine (20.7%), chlorpheniramine (19.5%), tramadol (9.8%), cimetidine (5.8%), and furosemide (3.6%). Polypharmacy, higher body mass index, less dependence, better communication and cognitive functions, and poorer quality of life were associated with high KABS. CONCLUSION: Although the patients with a high burden of DAPs were less dependent and had better cognitive and communication functions, they had poorer quality of life. DAP use in LTCH patients should be monitored carefully, and the risk/ benefit relationship for their use should be considered.


Assuntos
Antagonistas Colinérgicos , Assistência de Longa Duração , Idoso , Antagonistas Colinérgicos/efeitos adversos , Hospitais , Humanos , Polimedicação , Qualidade de Vida , República da Coreia/epidemiologia
18.
Cancer Biother Radiopharm ; 37(6): 417-423, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33434438

RESUMO

Background: The goal of this research was to investigate the feasibility of 64Cu labeling in prostate-specific membrane antigen imaging and therapy (PSMA I&T) for PSMA positron emission tomography (PET) imaging and biodistribution evaluation. Materials and Methods: PSMA I&T was labeled with 64Cu, and stability in human and mouse sera was evaluated. Prostate cancer cell lines were used for specific uptake assays (22RV1 for PSMA-positive, PC-3 for -negative). Both PC-3 and 22RV1 cells were transplanted into the left and right thighs in a mouse for PET/computed tomography (CT) imaging. Biodistribution was performed using 22RV1 tumor models. Results: Labeling yield (decay corrected) of 64Cu-PSMA I&T was more than 95% compared to the free 64Cu peak. The serum stability of 64Cu-PSMA I&T was maintained at more than 90% until 60 h. Regarding the specific binding of 64Cu-PSMA I&T was 7.5-fold higher to 22RV1 cells than PC-3 cells (p < 0.001). On PET/CT imaging, more specific 64Cu-PSMA I&T uptake was observed to 22RV1 tumors than to PC-3 tumors. In the PSMA blocking study using 2-phosphonomethoxypropyl adenine (2-PMPA), the 64Cu-PSMA I&T signal significantly decreased in the 22RV1 tumor region. In the biodistribution study, the kidney uptake was the highest among all organs at 2 h (52.6 ± 20.8%ID/g) but sharply decreased at 24 and 48 h. Also, the liver showed similar uptake over time (range, 10-12%ID/g). On the contrary, 64Cu-PSMA I&T uptake of the tumors increased with time and peaked at 48 h (5.6 ± 0.1%ID/g). Conclusions: PSMA I&T labeled with 64Cu showed the feasibility of the PSMA specific PET imaging through in vitro and in vivo studies. Furthermore, 64Cu-PSMA I&T might be considered as the candidate of future clinical trial.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Animais , Linhagem Celular Tumoral , Estudos de Viabilidade , Humanos , Masculino , Camundongos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos , Distribuição Tecidual
19.
Fish Shellfish Immunol ; 119: 490-498, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34715327

RESUMO

The present study investigated the virulence and expression of innate immunity genes in isolates of infectious hematopoietic necrosis virus (IHNV) in Gangwon province, South Korea, by challenging rainbow trout, Atlantic salmon, and coho salmon. Eight IHNV isolates were used to infect RTG-2 cells for viral replication using plaque assays. Three isolates with the highest replication rates, the RtPc0314g and RtPc0314c isolates of the JRt-Shizuoka type and the RtPc0816g isolate of the JRt-Nagano type, were experimentally infected into the fish. In rainbow trout, both RtPc0314c and RtPc0314g isolates showed 100% cumulative mortality while the RtPc0816g isolate showed 60% cumulative mortality for 14 days. In contrast, all three isolates showed <60% cumulative mortality in Atlantic salmon and coho salmon. The expression of G genes in the kidney was higher than that in the spleen-infected fish, with the highest expression observed in the kidneys of rainbow trout. The relative expression levels of innate immunity genes were higher in rainbow trout than in Atlantic salmon and coho salmon. The expression level of immunoglobulin M increased until day 7, and the expression of type I interferon was higher in the spleen than in other tissues. The expression of Mx-1 was higher in the kidney and liver than other tissues. These results indicate that IHNV isolates from Gangwon province show host-specific virulence in rainbow trout and that their virulence and replication were higher in JRt-Shizuoka type than in JRt-Nagano type isolates.


Assuntos
Doenças dos Peixes , Vírus da Necrose Hematopoética Infecciosa , Oncorhynchus mykiss , Infecções por Rhabdoviridae , Animais , Infecções por Rhabdoviridae/veterinária , Virulência
20.
J Shoulder Elbow Surg ; 30(12): 2814-2823, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34273535

RESUMO

PURPOSE: To evaluate the effects of diabetes and corticosteroid injected in the joints on the shoulder motion, gait, and joint capsular properties in a rat stiffness model. METHODS: A total of 27 rats were randomly distributed into 3 groups-nondiabetes group (group A), diabetes group (group B), and diabetes plus steroid injection group (group C). The diabetes model was developed by inducing hyperglycemia with a submaximal dose of streptozotocin and the stiffness model by completely immobilizing the right shoulder of each animal in all groups with sutures passed between the scapula and humeral shaft. The left shoulder was used as an untreated control in all groups. Three weeks after immobilization, the sutures were removed in all groups, and a single dose of triamcinolone acetonide (0.5 mg/kg) was injected into the glenohumeral joint in group C. After 3 weeks of free activity, range of motion (ROM) evaluation, gait analysis by stride length, and capsular area measurement were performed in all rats. RESULTS: Hyperglycemia was successfully induced with a mean blood glucose level of 448.9±55.9 mg/dL in group B and 431.6±17.8 mg/dL in group C, which were significantly higher than 136.5±13.4 mg/dL in group A (P < .001). A significantly smaller ROM and stride length were found in the right (stiffness-induced) shoulder than that in the left (control) shoulder only in group B, and significantly larger capsular area in the right shoulder than that in the left shoulder in groups A and B (all P < .05). However, in group C, there were no differences between the right and left shoulders in all measurements (all P > .05). In case of the right shoulders in each group, group C showed significantly larger ROM (68° ± 11° vs. 42° ± 7°) and smaller capsular area (3934.4 ± 537.1 pixels vs. 7402.3 ± 1840.3 pixels) than group B (all P < .0167). CONCLUSIONS: The diabetic model had a detrimental effect on the development of stiffness by thickening the joint capsule, and an intra-articular steroid injection resolved the thickened joint capsule and restored shoulder motion.


Assuntos
Diabetes Mellitus , Articulação do Ombro , Corticosteroides , Animais , Cápsula Articular , Amplitude de Movimento Articular , Ratos
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