RESUMEN
INTRODUCTION/AIMS: The care burden of people living with amyotrophic lateral sclerosis (pALS) increases with disease progression. This study aimed to investigate the home care status and preparedness of care partners of pALS (cALS) in Korea. METHODS: An online survey was conducted with family care partners of patients diagnosed with ALS for over 1 year in 2022. The data collected included care time, depression evaluated using the patient health questionnaire-9 (PHQ-9), preparedness for caregiving scale (PCS), and caregiver competence scale (CCS). Results were compared based on whether the pALS underwent a tracheostomy or not. RESULTS: Ninety-eight cALS of 98 pALS participated in the study, of whom 59 pALS had undergone tracheostomy. Among the cALS, 60.2% were spouses, and 34.7% were children. The cALS took care of the patients for 13 (8-20) hours/day (median, interquartile range [IQR]) on weekdays and 15 (10-24) h/day on weekends. Among the cALS, 91.8% were depressed, and 28.6% had severe depression. The median (IQR) PCS and CCS scores were low (11/32 (8-15) and 8/20 (8-11), respectively), and both were lower in those caring for patients without than with tracheostomy (p < .001 and p < .02, respectively). Most cALS (77.6%) wished to continue caring for their pALS at home. DISCUSSION: Family care partners of pALS spend more than half of each day caring for patients and are often depressed. Most cALS preferred providing care at home, but felt ill-prepared. Designing home-based medical care is necessary for pALS to thrive at home.
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Esclerosis Amiotrófica Lateral , Cuidadores , Humanos , Esclerosis Amiotrófica Lateral/terapia , Esclerosis Amiotrófica Lateral/psicología , Esclerosis Amiotrófica Lateral/enfermería , Masculino , República de Corea/epidemiología , Femenino , Cuidadores/psicología , Persona de Mediana Edad , Anciano , Adulto , Encuestas y Cuestionarios , Depresión/psicología , Depresión/terapia , Depresión/epidemiología , Servicios de Atención de Salud a Domicilio , Costo de Enfermedad , Traqueostomía , Esposos/psicología , Carga del Cuidador/psicologíaRESUMEN
INTRODUCTION: Patients with hematologic malignancies (HMs) often face challenges in accessing palliative care (PC) and receiving quality end-of-life (EOL) care. We examined factors associated with referrals to tertiary PC and the effects of tertiary PC on EOL care in patients with HMs. METHOD: We included patients with HMs who were admitted to a university-affiliated hospital and died during hospitalization between January 2018 and December 2021. We investigated the receipt of PC consultations, patient characteristics, and EOL care indicators. RESULTS: Overall, 487 patients were included in the analysis, with 156 (32%) undergoing PC consultation. Sex, residence, disease status, and admission purpose were factors associated with the likelihood of PC consultation, and there has been an increasing trend in the frequency of consultations in recent cases. A higher proportion of patients who received PC completed advance statements and life-sustaining treatment documents. Patients who received PC had lower rates of aggressive EOL care, including chemotherapy and intensive care unit admission, than those who did not receive PC. Notably, PC reduced the number of blood transfusions. CONCLUSION: Tertiary PC aims to reduce aggressive EOL care through patient-centered goal-of-care discussions. Therefore, there is an imperative need for concerted efforts toward seamless integration of PC.
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Neoplasias Hematológicas , Cuidados Paliativos al Final de la Vida , Neoplasias , Cuidado Terminal , Humanos , Cuidados Paliativos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/terapia , República de Corea/epidemiología , Estudios Retrospectivos , Neoplasias/terapiaRESUMEN
BACKGROUND: Despite medical advancements in neonatal survival rates, many children have poor neurological outcomes. Because the law in Korea restricts the withdrawal of life-sustaining treatment to only cases of imminent death, treatment discontinuation may not be an option, even in patients with poor neurological prognosis. This study investigated the opinions of the general population and clinicians regarding life-sustaining treatment withdrawal in such cases using hypothetical scenarios. METHODS: We conducted a cross-sectional study on the general population and clinicians using a web-based questionnaire. The sample of the general population from an online panel comprised 500 individuals aged 20-69 years selected by quota sampling. The clinician sample comprised 200 clinicians from a tertiary university hospital. We created hypothetical vignettes and questionnaire items to assess attitudes regarding mechanical ventilation withdrawal for an infant at risk of poor neurological prognosis due to birth asphyxia at 2 months and 3 years after the incidence. RESULTS: Overall, 73% of the general population and 74% of clinicians had positive attitudes toward mechanical ventilator withdrawal at 2 months after birth asphyxia. The proportion of positive attitudes toward mechanical ventilator withdrawal was increased in the general population (84%, P < 0.001) and clinicians (80.5%, P = 0.02) at 3 years after birth asphyxia. Religion, spirituality, the presence of a person with a disability in the household, and household income were associated with the attitudes of the general population. In the multivariable logistic regression analysis of the general population, respondents living with a person with a disability or having a disability were more likely to find the withdrawal of the ventilator at 2 months and 3 years after birth asphyxia not permissible. Regarding religion, respondents who identified as Christians were more likely to find the ventilator withdrawal at 2 months after birth asphyxia unacceptable. CONCLUSION: The general population and clinicians shared the perspective that the decision to withdraw life-sustaining treatment in infants with a poor neurological prognosis should be considered before the end of life. A societal discussion about making decisions centered around the best interest of pediatric patients is warranted.
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Respiración Artificial , Privación de Tratamiento , Humanos , Masculino , Femenino , Adulto , Pronóstico , Encuestas y Cuestionarios , Privación de Tratamiento/legislación & jurisprudencia , Persona de Mediana Edad , Estudios Transversales , Lactante , Anciano , Adulto Joven , Recién Nacido , Asfixia Neonatal/terapia , República de Corea , Actitud del Personal de SaludRESUMEN
OBJECTIVES: Issues regarding antibiotic use in end-of-life patients with advanced cancer present a challenging ethical dilemma in academic referral centres. This study aimed to investigate the role of palliative care consultation on antibiotic prescription patterns among hospitalized patients with advanced cancer during their last days of life. METHODS: This retrospective cohort study included adult patients with metastatic solid cancer admitted to a tertiary referral hospital for at least 4 days and subsequently died and who were given antibiotics 4 days before death between January 2018 and December 2021. Patients were divided into palliative care consultation (PC) and non-consultation (non-PC) groups. The outcomes were the proportion of patients who received antibiotic combination treatment, antibiotic escalation and antibiotic de-escalation within 3 days of death. Propensity score analysis with the inverse probability of the treatment weighting method was used to compare the outcomes. RESULTS: Among the 1177 patients enrolled, 476 (40.4%) received palliative care consultation and 701 (59.6%) did not. The PC group received considerably less antibiotic combination treatment (49.0% versus 61.1%, adjusted OR: 0.69, 95% CI: 0.53-0.90, Pâ=â0.006) and antibiotic escalation (15.8% versus 34.8%, adjusted OR: 0.41, 95% CI: 0.30-0.57, Pâ<â0.001) than the non-PC group. Additionally, the PC group reported significantly higher antibiotic de-escalation (30.7% versus 17.4%, adjusted OR: 1.74, 95% CI: 1.28-2.36, Pâ<â0.001). CONCLUSION: Receiving palliative care consultation may minimize aggressive antibiotic prescription patterns in the last days of patients with advanced cancer in an academic referral centre setting.
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Neoplasias , Cuidados Paliativos , Adulto , Humanos , Cuidados Paliativos/métodos , Estudios Retrospectivos , Neoplasias/tratamiento farmacológico , Derivación y Consulta , Centros de Atención TerciariaRESUMEN
INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) inevitably visit the emergency department (ED) due to their increased risk of respiratory failure and mobility limitations. However, nationwide data on ED visits by patients with ALS are limited. This study investigated the characteristics of patients with ALS-related ED visits. METHODS: We conducted a cross-sectional study from 2016 to 2020, utilizing a nationwide ED database. The total number of patients with ALS who visited the ED and their primary reasons for visiting/diagnoses were analyzed. RESULTS: In total, 6036 visits to the ED were made by patients with ALS. Of these, 41.8% arrived by ambulance and 27.7% spent >9 h in the ED. Following ED treatment, 57.4% were hospitalized, including 19.3% admitted to the intensive care unit (ICU) and 5.4% who died in the hospital. The primary reasons for ALS-related ED visits were dyspnea (35.2%), feeding tube problems (10.1%), fever (7.8%), and mental status changes (3.6%). The most common diagnoses were pneumonia (14.5%), respiratory failure (5.7%), dyspnea (5.5%), aspiration pneumonia (4.3%), and tracheostomy complications (3.4%). DISCUSSION: Reasons for ED visits for patients with ALS include acute respiratory distress, as well as concerns related to tube feeding and tracheostomy. To reduce the risk of patients with ALS requiring ED visits, it is essential to ensure the provision of timely respiratory support and high-quality home-based medical care teams that can support and address patients before their condition deteriorates.
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Esclerosis Amiotrófica Lateral , Insuficiencia Respiratoria , Humanos , Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/terapia , Estudios Transversales , Servicio de Urgencia en Hospital , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Disnea , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
Atrial fibrillation (AF) is the most common form of sustained clinical arrhythmia. We previously mapped an AF locus to chromosome 5p13 in an AF family with sudden death in early childhood. Here we show that the specific AF gene underlying this linkage is NUP155, which encodes a member of the nucleoporins, the components of the nuclear pore complex (NPC). We have identified a homozygous mutation, R391H, in NUP155 that cosegregates with AF, affects nuclear localization of NUP155, and reduces nuclear envelope permeability. Homozygous NUP155(-/-) knockout mice die before E8.5, but heterozygous NUP155(+/-) mice show the AF phenotype. The R391H mutation and reduction of NUP155 are associated with inhibition of both export of Hsp70 mRNA and nuclear import of Hsp70 protein. These human and mouse studies indicate that loss of NUP155 function causes AF by altering mRNA and protein transport and link the NPC to cardiovascular disease.
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Fibrilación Atrial/genética , Muerte Súbita Cardíaca , Proteínas de Complejo Poro Nuclear/genética , Secuencia de Aminoácidos , Animales , Femenino , Proteínas del Choque Térmico HSP72/genética , Proteínas del Choque Térmico HSP72/metabolismo , Humanos , Masculino , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Membrana Nuclear/metabolismo , Proteínas de Complejo Poro Nuclear/metabolismo , Linaje , Alineación de SecuenciaRESUMEN
BACKGROUND: Clinical ethics support is a form of preventive ethics aimed at mediating ethics-related conflicts and managing ethical issues arising in the healthcare setting. However, limited evidence exists regarding the specific ethical issues in clinical practice. This study aimed to explore the diverse ethical issues of cases referred to clinical ethics support after the new legislation on hospice palliative care and end-of-life decision-making was implemented in Korea in 2018. METHODS: A retrospective study of cases referred to clinical ethics support at a university hospital in Korea from February 2018 to February 2021 was conducted. The ethical issues at the time of referral were analyzed via qualitative content analysis of the ethics consultation-related documents. RESULTS: A total of 60 cases of 57 patients were included in the study, of whom 52.6% were men and 56.1% were older than 60 years of age. The majority of cases (80%) comprised patients from the intensive care unit. One-third of the patients were judged as being at the end-of-life stage. The most frequent ethical categories were identified as goals of care/treatment (78.3%), decision-making (75%), relationship (41.7%), and end-of-life issues (31.7%). More specifically, best interests (71.7%), benefits and burdens/harms (61.7%), refusal (53.3%), and surrogate decision-making (33.3%), followed by withholding or withdrawal (28.3%) were the most frequent ethical issues reported, which became diversified by year. In addition, the ethical issues appeared to differ by age group and judgment of the end-of-life stage. CONCLUSION: The findings of this study expand the current understanding of the diverse ethical issues including decision-making and goals of care/treatment that have been referred to clinical ethics support since the enforcement of the new legislation in Korea. This study suggests a need for further research on the longitudinal exploration of ethical issues and implementation of clinical ethics support in multiple healthcare centers.
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Consultoría Ética , Ética Clínica , Masculino , Humanos , Femenino , Toma de Decisiones , Estudios Retrospectivos , Hospitales Universitarios , Muerte , República de CoreaRESUMEN
BACKGROUND: Healthcare professionals often experience moral distress while providing end-of-life care. This study explored how physicians and nurses experienced moral distress when they cared for critically and terminally ill patients in tertiary hospitals in South Korea. METHODS: This study used semi-structured in-depth interviews. A total of 22 people in two tertiary hospitals were interviewed, nine (40.9%) of which were physicians and 13 (59.1%) were nurses. The recorded interview files and memos were analyzed using grounded theory. RESULTS: Most physicians and nurses encountered similar feelings of anger, helplessness, and burden owing to a lack of appropriate resources for end-of-life care. However, the factors and contexts of their moral distress differed. Nurses mainly addressed poorly organized end-of-life care, intensive labor conditions without support for nurses, and providing care without participation in decision-making. Meanwhile, physicians addressed the prevailing misperceptions on end-of-life care, communication failure between physicians owing to hierarchy and fragmented disciplines, the burden of responsibility in making difficult decisions, and the burden of resource allocation. CONCLUSION: Differences in moral distress between physicians and nurses leave them isolated and can affect communication regarding healthcare. Mutual understanding between job disciplines will enhance their communication and help resolve conflicts in end-of-life care.
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Enfermeras y Enfermeros , Médicos , Cuidado Terminal , Humanos , Hospitales Universitarios , Actitud del Personal de Salud , Principios Morales , Estrés Psicológico , Encuestas y CuestionariosRESUMEN
OBJECTIVES: A substantial number of hospitalized patients with terminal cancer at the end-of-life phase receive antibiotics, even with imminent death. We evaluated the impact of palliative care consultation on antibiotic use in hospitalized patients with terminal cancer during the end-of-life phase. METHODS: We identified adult patients with metastatic solid cancer who died at a tertiary medical centre in Seoul, Republic of Korea, following at least 4â days of hospitalization (January 2018-December 2020). Patients were divided into palliative and non-palliative care consultation groups. Propensity score-weighted, multivariable logistic regression analysis was used to compare the proportion of patients receiving antibiotics within 3â days before death between the two groups. RESULTS: Among 1143 patients analysed, 940 (82.2%) received antibiotics within 3â days before death. The proportion of patients receiving antibiotics was significantly lower (propensity score-weighted Pâ<â0.001) in the palliative care consultation group (344/468; 73.5%) than in the non-palliative care consultation group (596/675; 88.3%). The decrease in the proportion of patients receiving antibiotics in the palliative care consultation group was significant for a carbapenem (42.4% versus 22.4%; Pâ<â0.001), a glycopeptide (23.3% versus 11.1%; Pâ<â0.001) and a quinolone (30.5% versus 19.4%; Pâ=â0.012). In the multivariable logistic regression analysis, receiving palliative care consultation (adjusted OR 0.46, 95% CI 0.33-0.65; Pâ<â0.001) was independently associated with reduced antibiotic use during the end-of-life phase. CONCLUSIONS: Palliative care consultation may reduce aggressive antibiotic use in hospitalized patients with terminal cancer during the end-of-life phase.
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Antibacterianos , Neoplasias , Adulto , Humanos , Puntaje de Propensión , Antibacterianos/uso terapéutico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Derivación y Consulta , Muerte , Estudios RetrospectivosRESUMEN
PURPOSE: This study investigated the antiadhesive effects of Mediclore®, rosuvastatin, and a combination of Mediclore and rosuvastatin in a rat adhesion model. METHODS: The adhesion models (a total of 58 adult male rats) were divided into 4 groups. The control group (group C) received no special materials except for a saline. The experimental groups were treated with 5 mL of Mediclore (group M), rosuvastatin (group R), or rosuvastatin and Mediclore (group RM), and these materials were intraperitoneally placed under the incision. At postoperative day 14, the rats underwent re-laparotomy and adhesiolysis. Three investigators blinded to group assignment scored the extent of adhesion formation, the numbers of remote adhesions, and the extent of acute/chronic inflammation, fibrosis, edema, and congestion on resected specimens via histologic examination. RESULTS: The macroscopic adhesion score in group RM (7.27 ± 3.51) was significantly lower than those in groups C (13.36 ± 2.24) and R (11.71 ± 1.98); group M (9.13 ± 4.09) had a significantly lower adhesion score than group C. The number of remote adhesions was significantly lower in groups R and RM than in group C. The acute inflammation score, chronic inflammation score, and fibrosis score in group RM; the acute inflammation score in group R; and the fibrosis score in group M were significantly lower than those in group C. CONCLUSION: The intraperitoneal application of Mediclore and a combination of Mediclore and rosuvastatin effectively reduced postoperative adhesions.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Animales , Modelos Animales de Enfermedad , Fibrosis , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , Inflamación/prevención & control , Masculino , Complicaciones Posoperatorias/prevención & control , Ratas , Rosuvastatina Cálcica/farmacología , Adherencias Tisulares/prevención & controlRESUMEN
BACKGROUND: High-quality end-of-life (EOL) care requires both comfort care and the maintenance of dignity. However, delivering EOL in the emergency department (ED) is often challenging. Therefore, we aimed to investigate characteristics of EOL care for dying patients in the ED. METHODS: We conducted a retrospective cohort study of patients who died of disease in the ED at a tertiary hospital in Korea between January 2018 and December 2020. We examined medical care within the last 24 h of life and advance care planning (ACP) status. RESULTS: Of all 222 disease-related mortalities, 140 (63.1%) were men, while 141 (63.5%) had cancer. The median age was 74 years. As for critical care, 61 (27.5%) patients received cardiopulmonary resuscitation, while 80 (36.0%) received mechanical ventilation. The absence of serious illness (p = 0.011) and the lack of an advance statement (p < 0.001) were both independently associated with the receipt of more critical care. Only 70 (31.5%) patients received comfort care through opioids. Younger patients (< 75 years) (p = 0.002) and those who completed life-sustaining treatment legal forms (p = 0.001) received more comfort care. While EOL discussions were initiated in 150 (67.6%) cases, the palliative care team was involved only in 29 (13.1%). CONCLUSIONS: Patients in the ED underwent more aggressive care and less comfort care in a state of imminent death. To ensure better EOL care, physicians should minimize redundant evaluations and promptly introduce ACP.
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Planificación Anticipada de Atención , Neoplasias , Cuidado Terminal , Anciano , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Neoplasias/terapia , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
BACKGROUND: Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments of AF are suboptimal because they are not targeted to the molecular mechanisms underlying AF. Using a highly novel gene therapy approach in a canine, rapid atrial pacing model of AF, we demonstrate that NADPH oxidase 2 (NOX2) generated oxidative injury causes upregulation of a constitutively active form of acetylcholine-dependent K+ current (IKACh), called IKH; this is an important mechanism underlying not only the genesis, but also the perpetuation of electric remodeling in the intact, fibrillating atrium. METHODS: To understand the mechanism by which oxidative injury promotes the genesis and maintenance of AF, we performed targeted injection of NOX2 short hairpin RNA (followed by electroporation to facilitate gene delivery) in atria of healthy dogs followed by rapid atrial pacing. We used in vivo high-density electric mapping, isolation of atrial myocytes, whole-cell patch clamping, in vitro tachypacing of atrial myocytes, lucigenin chemiluminescence assay, immunoblotting, real-time polymerase chain reaction, immunohistochemistry, and Masson trichrome staining. RESULTS: First, we demonstrate that generation of oxidative injury in atrial myocytes is a frequency-dependent process, with rapid pacing in canine atrial myocytes inducing oxidative injury through the induction of NOX2 and the generation of mitochondrial reactive oxygen species. We show that oxidative injury likely contributes to electric remodeling in AF by upregulating IKACh by a mechanism involving frequency-dependent activation of PKCε (protein kinase C epsilon). The time to onset of nonsustained AF increased by >5-fold in NOX2 short hairpin RNA-treated dogs. Furthermore, animals treated with NOX2 short hairpin RNA did not develop sustained AF for up to 12 weeks. The electrophysiological mechanism underlying AF prevention was prolongation of atrial effective refractory periods, at least in part attributable to the attenuation of IKACh. Attenuated membrane translocation of PKCε appeared to be a likely molecular mechanism underlying this beneficial electrophysiological remodeling. CONCLUSIONS: NOX2 oxidative injury (1) underlies the onset, and the maintenance of electric remodeling in AF, as well, and (2) can be successfully prevented with a novel, gene-based approach. Future optimization of this approach may lead to a novel, mechanism-guided therapy for AF.
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Fibrilación Atrial , Remodelación Atrial , Regulación Enzimológica de la Expresión Génica , Terapia Genética , NADPH Oxidasa 2 , ARN Interferente Pequeño , Animales , Fibrilación Atrial/enzimología , Fibrilación Atrial/genética , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Perros , Atrios Cardíacos/enzimología , Atrios Cardíacos/fisiopatología , NADPH Oxidasa 2/biosíntesis , NADPH Oxidasa 2/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismoRESUMEN
BACKGROUND: Immune checkpoint inhibitor (ICI) has an emerging role in several types of cancer. However, the mechanisms of acquired resistance (AR) to ICI have not been elucidated yet. To identify these mechanisms, we analyzed the pre- and post-ICI paired tumor samples in patients with AR. METHODS: Six patients with renal cell carcinoma, urothelial cell carcinoma, or head and neck cancer, who showed an initial response to ICI followed by progression and had available paired tissue samples, were retrospectively analyzed. Whole exome sequencing, RNA sequencing, and multiplex immunohistochemistry were performed on pre-treatment and resistant tumor samples. RESULTS: The median time to AR was 370 days (range, 210 to 739). Increased expression of alternative immune checkpoints including TIM3, LAG3, and PD-1 as well as increased CD8+ tumor-infiltrating lymphocytes were observed in post-treatment tumor than in pre-treatment tumor of a renal cell carcinoma patient. In contrast, CD8+ T cells and immunosuppressive markers were all decreased at AR in another patient with human papillomavirus-positive head and neck squamous cell carcinoma. This patient had an evident APOBEC-associated signature, and the tumor mutation burden increased at AR. Resistant tumor tissue of this patient harbored a missense mutation (E542K) in PIK3CA. No significant aberrations of antigen-presenting machinery or IFN-γ pathway were detected in any patient. CONCLUSIONS: Our study findings suggest that the observed increase in immunosuppressive markers after ICI might contribute to AR. Moreover, APOBEC-mediated PIK3CA mutagenesis might be an AR mechanism. To validate these mechanisms of AR, further studies with enough sample size are required.
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Biomarcadores de Tumor/genética , Carcinoma de Células Renales/patología , Resistencia a Antineoplásicos/genética , Neoplasias de Cabeza y Cuello/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/patología , Neoplasias Urológicas/patología , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Masculino , Pronóstico , RNA-Seq , Estudios Retrospectivos , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/genética , Secuenciación del ExomaRESUMEN
Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments for AF are suboptimal as they are not targeting the molecular mechanisms underlying AF. In this regard, gene therapy is emerging as a promising approach for mechanism-based treatment of AF. In this review, we summarize recent advances and challenges in gene therapy for this important cardiovascular disease.
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Fibrilación Atrial , Accidente Cerebrovascular , Adulto , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/genética , Fibrilación Atrial/terapia , Terapia Genética , HumanosRESUMEN
BACKGROUND: Phosphorylation of NF-kappaB inhibitor alpha (IκBα) is key to regulation of NF-κB transcription factor activity in the cell. Several sites of IκBα phosphorylation by members of the IκB kinase family have been identified, but phosphorylation of the protein by other kinases remains poorly understood. We investigated a new phosphorylation site on IκBα and identified its biological function in breast cancer cells. METHODS: Previously, we observed that aurora kinase (AURK) binds IκBα in the cell. To identify the domains of IκBα essential for phosphorylation by AURK, we performed kinase assays with a series of IκBα truncation mutants. AURK significantly promoted activation of IκBα at serine 32 but not serine 36; by contrast, IκB kinase (IKK) family proteins activated both of these residues. We also confirmed phosphorylation of IκBα by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and nano-liquid chromatography hybrid quadrupole orbitrap mass spectrometer (nanoLC-MS/MS; Q-Exactive). RESULTS: We identified two novel sites of serine phosphorylation, S63 and S262. Alanine substitution of S63 and S262 (S63A and S262A) of IκBα inhibited proliferation and suppressed p65 transcription activity. In addition, S63A and/or S262A of IκBα regulated apoptotic and necroptotic effects in breast cancer cells. CONCLUSIONS: Phosphorylation of IκBα by AURK at novel sites is related to the apoptosis and necroptosis pathways in breast cancer cells.
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Aurora Quinasa C/metabolismo , Neoplasias de la Mama/patología , Inhibidor NF-kappaB alfa/metabolismo , Necroptosis , Sitios de Unión/genética , Femenino , Humanos , Células MCF-7 , Mutagénesis Sitio-Dirigida , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/aislamiento & purificación , FN-kappa B/metabolismo , Fosforilación , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
PURPOSE: A caregiver's prognostic awareness can affect clinical decisions for the patient. The purpose of this study was to examine the impact of family caregivers' prognostic awareness on the quality of life (QOL) and emotional state of both patients with advanced cancer and their caregivers. METHODS: This prospective cohort study was conducted from December of 2016 to January of 2018. A total of 159 patients with advanced cancer and an equal number of caregivers participated. The investigation tools used include the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-Palliative, the McGill Quality of Life Questionnaire, and the Patient Health Questionnaire-9, and evaluation was performed at baseline, 3 months, and 6 months. Covariance analysis with a general linear modeling was used to compare changes in quality of life scores according to the caregivers' awareness of the prognosis. RESULTS: Mean patient overall QOL score increased in the group of caregivers who were aware of prognosis and decreased in the caregivers who were not aware of the prognosis (p = 0.018). The changes over time in the patients' QOL scores associated with symptoms improved with caregiver awareness (pain, p = 0.017; dyspnea, p = 0.048; appetite loss, p = 0.045). The percentage of depressed patients was smaller after 3 months in the group with caregivers aware of the prognosis (baseline to 3 months p = 0.028). Caregivers who did not understand their patients' prognosis exhibited better existential well-being (p = 0.036), and the incidence of depression was lower in this group at 3 months (p = 0.024). CONCLUSION: Caregivers' prognostic awareness may improve the quality of life and mood in patients with advanced cancer; however, this awareness may harm the quality of life and mood of the caregivers. These results may aid in developing in-depth interventions regarding prognosis for both patients and their caregivers.
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Cuidadores/psicología , Depresión/epidemiología , Neoplasias/mortalidad , Neoplasias/terapia , Calidad de Vida/psicología , Adulto , Afecto , Anciano , Concienciación , Depresión/psicología , Emociones , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Neoplasias/psicología , Pronóstico , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
PURPOSE: Little has been determined regarding the association between patients' and families' illness understanding and preferences for medical care. We aimed to evaluate the association of illness understanding with advance care planning (ACP) and preferences for end-of-life care, such as aggressive care, early palliative care (EPC), and hospice care, among advanced cancer patients and their family caregivers. METHODS: Patients were recruited for a prospective cohort study at outpatient and inpatient facilities in nine university hospitals in Korea (n = 150), and their primary family caregivers were also asked to participate (n = 101). Data on ACP and end-of-life care preferences were collected only at baseline in the cohort study with optional questions and were used to analyze these study results. RESULTS: Patients with illness understanding were more likely to have documented physician orders for life-sustaining treatment (POLSTs) (adjusted odds ratio [aOR] of 4.94) and to have discussed ACP with their families (aOR 2.15) than those who did not. Being expected to live for several months, they were unlikely to prefer active treatment. Caregivers understanding patients' illness were more likely to write advance directives (ADs) and to discuss ACP; furthermore, they had already discussed ACP with family members. They did not prefer active treatment or life-sustaining treatments when their family members were expected to die within a few weeks. There was no significant association between illness understanding and preferences for EPC. CONCLUSION: Accurately recognizing an incurable disease is associated with preferences for more ACP and less aggressive care but not with preferences for EPC or hospice care among both advanced cancer patients and their family caregivers.
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Planificación Anticipada de Atención , Comprensión , Neoplasias/terapia , Prioridad del Paciente , Cuidado Terminal , Planificación Anticipada de Atención/estadística & datos numéricos , Directivas Anticipadas/psicología , Directivas Anticipadas/estadística & datos numéricos , Anciano , Cuidadores/psicología , Estudios de Cohortes , Comprensión/fisiología , Progresión de la Enfermedad , Familia/psicología , Femenino , Cuidados Paliativos al Final de la Vida/psicología , Cuidados Paliativos al Final de la Vida/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/patología , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Cuidados Paliativos/estadística & datos numéricos , Prioridad del Paciente/psicología , Prioridad del Paciente/estadística & datos numéricos , Estudios Prospectivos , República de Corea/epidemiología , Cuidado Terminal/psicología , Cuidado Terminal/estadística & datos numéricosRESUMEN
CONTEXT: As a novel coronavirus swept the world in early 2020, thousands of software developers began working from home. Many did so on short notice, under difficult and stressful conditions. OBJECTIVE: This study investigates the effects of the pandemic on developers' wellbeing and productivity. METHOD: A questionnaire survey was created mainly from existing, validated scales and translated into 12 languages. The data was analyzed using non-parametric inferential statistics and structural equation modeling. RESULTS: The questionnaire received 2225 usable responses from 53 countries. Factor analysis supported the validity of the scales and the structural model achieved a good fit (CFI = 0.961, RMSEA = 0.051, SRMR = 0.067). Confirmatory results include: (1) the pandemic has had a negative effect on developers' wellbeing and productivity; (2) productivity and wellbeing are closely related; (3) disaster preparedness, fear related to the pandemic and home office ergonomics all affect wellbeing or productivity. Exploratory analysis suggests that: (1) women, parents and people with disabilities may be disproportionately affected; (2) different people need different kinds of support. CONCLUSIONS: To improve employee productivity, software companies should focus on maximizing employee wellbeing and improving the ergonomics of employees' home offices. Women, parents and disabled persons may require extra support.
RESUMEN
While recently extending that research, however, we discovered that 236 members of the general population were mistakenly duplicated by the investigating agency (Word Research) and 1241 were reported rather than 1005. Here, we present corrections and discuss the relevant data.
RESUMEN
In the original publication of the article, the incorrect grant number HC13C1391 was published in the acknowledgement section. The correct grant number is HC15C1391.