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1.
Mayo Clin Proc ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093271

RESUMO

OBJECTIVE: To investigate the incidence, characteristics, and outcomes of COVID-19 vaccine-related pericarditis (VRP) without myocarditis, we analyzed nationwide Korean data. PATIENTS AND METHODS: This is a retrospective nationwide report including all vaccinated Koreans with COVID-19 vaccine of any platform (BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S) from February 26 to December 31, 2021. We analyzed the confirmed cases of COVID-19 VRP by the Expert Adjudication Committee. The incidence, clinical characteristics, and outcomes of COVID-19 VRP were analyzed. RESULTS: Among 44,322,068 Koreans with least one dose of COVID-19 vaccination, COVID-19 VRP was confirmed in 179 cases, with 1.73 per million shots (95% CI, 1.48 to 2.00 per million shots). The incidence of VRP was significantly higher in males than females (2.01 per 1 million doses vs 1.45 per 1 million doses, respectively; P=.029), in mRNA vaccines than in other vaccines (2.09 per 1 million doses vs 0.36 per 1 million doses, respectively; P<.001), and in those younger than 40 years of age than those older than 40 years of age (3.52 per 1 million doses vs 0.89 per 1 million doses, respectively; P<.001). The incidence of VRP was highest in males between the ages of 12 and 17 years (7.38 per 1 million doses; 95% CI, 2.01 to 16.07). Although there was no case of mortality, hemodynamically significant pericardial effusion requiring pericardial drainage was noted in 10 cases (5.6%). CONCLUSION: COVID-19 VRP was very rare and developed mainly in association with mRNA vaccines, especially in males younger than 40 years of age. The clinical course of VRP was excellent, and there were no cases of mortality. However, the development of hemodynamically significant pericardial effusion should be carefully monitored.

2.
Gerodontology ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38988103

RESUMO

OBJECTIVE: The purpose of this study was to establish an oral health activity assessment tool for older people and evaluate its validity. BACKGROUND: To provide reasonable and efficient oral health promotion services with limited medical resources, a tool including categories and items of oral health promotion activities for older people should be prepared. MATERIALS AND METHODS: The tool initially consisted of 76 items on oral health promotion activities for older people classified into assessment-performance-evaluation stages. Topics for each stage included general and oral health, daily health, oral health status, behaviour, and awareness. In addition, two Delphi surveys were conducted on 10 experts who met the selection criteria, and the final items were derived based on the review opinions. RESULTS: As a result of the first and second Delphi surveys, the content validity for all items was ≥0.60 and the content validity index was ≥0.80. In the first survey, the degree of convergence in some items was 0-0.88. After modifying the contents according to expert opinions, the degree of convergence was improved from 0 to 0.50 in the second survey. The degree of agreement ranged from 0.75 to 1.00, indicating that experts agreed. Finally, a total of 65 items were derived. CONCLUSION: A 65-item tool was derived through two Delphi surveys for the assessment of oral health activities for older people. The use of the tool developed in this study would likely contribute to better prevention of oral diseases and the promotion of oral health among older people.

3.
Adv Mater ; : e2403392, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011793

RESUMO

Understanding the intricate details of the surface atomic structure and composition of catalysts during the oxygen evolution reaction (OER) is crucial for developing catalysts with high stability in water electrolyzers. While many notable studies highlight surface amorphization and reconstruction, systematic analytical tracing of the catalyst surface as a function of overpotential remains elusive. Heteroepitaxial (001) films of chemically stable and lattice-oxygen-inactive LaCoO3 are thus utilized as a model catalyst to demonstrate a series of atomic-resolution observations of the film surface at different anodic potentials. The first key finding is that atoms at the surface are fairly dynamic even at lower overpotentials. Angstrom-scale atomic displacements within the perovskite framework are identified below a certain potential level. Another noteworthy feature is that amorphization (or paracrystallization) with no long-range order is finally induced at higher overpotentials. In particular, surface analyses consistently support that the oxidation of lattice oxygen is coupled with amorphous phase formation at the high potentials. Theoretical calculations also reveal an upward shift of oxygen 2p states toward the Fermi level, indicating enhanced lattice oxygen activation when atom displacement occurs more extensively. This study emphasizes that the degradation behavior of OER catalysts can distinctively vary depending on the overpotential level.

4.
J Adv Res ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019109

RESUMO

INTRODUCTION: Post-mastectomy radiotherapy plays a crucial role in breast cancer treatment but can lead to an inflammatory response causing soft tissue damage, particularly radiation-induced capsular contracture (RICC), impacting breast reconstruction outcomes. Adipose-derived stem cells (ADSCs), known for their regenerative potential via paracrine capacity, exhibit inherent radiotolerance. The influence of tumor necrosis factor-alpha (TNF-α) on ADSCs has been reported to enhance the paracrine effect of ADSCs, promoting wound healing by modulating inflammatory responses. OBJECTIVE: This study investigates the potential of TNF-α-treated human ADSCs (T-hASCs) on silicone implants to alleviate RICC, hypothesizing to enhance suppressive effects on RICC by modulating inflammatory responses in a radiation-exposed environment. METHODS: In vitro, T-hASCs were cultured on various surfaces to assess viability after exposure to radiation up to 20 Gy. In vivo, T-hASC and non-TNF-α-treated hASC (C-hASCs)-coated membranes were implanted in mice before radiation exposure, and an evaluation of the RICC mitigation took place 4 and 8 weeks after implantation. In addition, the growth factors released from T-hASCs were assessed. RESULTS: In vitro, hASCs displayed significant radiotolerance, maintaining consistent viability after exposure to 10 Gy. TNF-α treatment further enhanced radiation tolerance, as evidenced by significantly higher viability than C-hASCs at 20 Gy. In vivo, T-hASC-coated implants effectively suppressed RICC, reducing capsule thickness. T-hASCs exhibited remarkable modulation of the inflammatory response, suppressing M1 macrophage polarization while enhancing M2 polarization. The elevated secretion of vascular endothelial growth factor from T-hASCs is believed to induce macrophage polarization, potentially reducing RICC. CONCLUSION: This study establishes T-hASCs as a promising strategy for ameliorating the adverse effects experienced by breast reconstruction patients after mastectomy and radiation therapy. The observed radiotolerance, anti-fibrotic effects, and immune modulation suggest the possibility of enhancing patient outcomes and quality of life. Further research and clinical trials are warranted for broader clinical uses.

5.
J Glaucoma ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38995126

RESUMO

PRCIS: Glaucoma eyes with recurrent disc hemorrhage were associated with increased systolic blood pressure and diastolic blood pressure, and increased visit-to-visit diastolic blood pressure variability was associated with glaucoma progression. PURPOSE: In this study, we investigated the effects of the clinical characteristics of disc hemorrhage (DH) and hemodynamic factors on glaucoma progression. METHODS: This retrospective cohort study included 81 eyes with open angle glaucoma and non-recurrent or recurrent DH. Recurrent DH was further classified according to the DH location. Visual field (VF) progression was determined using event-based analysis and Guided Progression Analysis software. The coefficient of variation (CV) of systolic and diastolic blood pressure (SBP and DBP, respectively) was used to measure visit-to-visit variability. Kaplan-Meier survival analysis was used to compare the cumulative risk ratio of progression between groups. RESULTS: The recurrent DH group had significantly higher SBP and DBP (P=0.014 and=0.021, respectively) and a higher proportion of VF progression (P=0.019) than the non-recurrent DH group. In particular, females with recurrent DH had the highest cumulative probability of VF progression (P=0.047, log-rank test). Recurrent DH in a different quadrant was associated with the highest cumulative probability of VF progression than non-recurrent DH (P=0.038, log-rank test). In Cox regression analysis, higher visit-to-visit DBP variability, female sex, and recurrent DH in a different quadrant were significantly associated with glaucoma progression. CONCLUSION: In glaucomatous eyes with DH, increased visit-to-visit DBP variability was associated with glaucoma progression. Our results suggest that hemodynamic factors are involved in the recurrence of DH and progression of glaucoma.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38997856

RESUMO

BACKGROUND: The efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC. DATA SOURCES: A comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included. RESULTS: A total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768-1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764-1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451-0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563-1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642-1.214) showed any significant effect on the OS. CONCLUSIONS: The effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.

7.
Alzheimers Dement ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39001624

RESUMO

INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.

8.
Adv Mater ; : e2406179, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39003621

RESUMO

Hydroxyapatite (HA) exhibits outstanding biocompatibility, bioactivity, osteoconductivity, and natural anti-inflammatory properties. Pure HA, ion-doped HA, and HA-polymer composites are investigated, but critical limitations such as brittleness remain; numerous efforts are being made to address them. Herein, the novel self-crystallization of a polymeric single-stranded deoxyribonucleic acid (ssDNA) without additional phosphate ions for synthesizing deoxyribonucleic apatite (DNApatite) is presented. The synthesized DNApatite, DNA1Ca2.2(PO4)1.3OH2.1, has a repetitive dual phase of inorganic HA crystals and amorphous organic ssDNA at the sub-nm scale, forming nanorods. Its mechanical properties, including toughness and elasticity, are significantly enhanced compared with those of HA nanorod, with a Young's modulus similar to that of natural bone.

9.
BMJ Open ; 14(7): e084052, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38955368

RESUMO

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) plays an indispensable role in treating pancreato-biliary diseases but carries a risk of post-ERCP pancreatitis (PEP). Despite advances in the prevention strategies, prevention of PEP remains imperfect, necessitating more refined hydration methods. This study investigates the effectiveness of lactated Ringer's solution versus plasma solution in preventing PEP. METHOD AND ANALYSIS: This multicentre, double-blind, randomised controlled trial, will be initiated by the investigator-sponsor, and conducted in three tertiary centres in South Korea. The aim of this study is to assess the effectiveness of hydration in preventing PEP in patients with naïve papillae. It will target patients with naïve papillae, focusing on those at medium to high risk of PEP. Patients aged ≤18 years and those with serious comorbidities, acute/chronic pancreatitis and various other medical conditions will be excluded. Eligible participants will be randomly assigned into two arms in equal numbers: (1) PEP prevention using lactated Ringer's solution and (2) PEP prevention using plasma solution. The primary outcome of this study will be the occurrence of PEP, and secondary outcomes will be additional risk factors and potential adverse events related to ERCP. With a total enrolment of 844 patients, the study will be able to detect significant differences between the intervention arms. ETHICS AND DISSEMINATION: Ethical approval is obtained from each institution (Asan Medical Centre, 2023-0382; Seoul National University Hospital, H-2302-05-1404; Samsung Medical Centre, SMC 2023-02-001-009). All participants provided informed consent following clear explanation of the study procedures. The results of the study will be disseminated in peer-reviewed journals and research conferences. TRIAL REGISTRATION NUMBER: NCT05832047. PROTOCOL VERSION: Ver 4.1 (2023).


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Pancreatite , Lactato de Ringer , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/prevenção & controle , Pancreatite/etiologia , Método Duplo-Cego , Lactato de Ringer/administração & dosagem , República da Coreia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Hidratação/métodos , Masculino , Feminino
10.
Res Sq ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38947089

RESUMO

Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

11.
Mycobiology ; 52(3): 201-206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948449

RESUMO

The species within the family Cunninghamellaceae during an investigation of soil microfungi in Korea, in which three strains were isolated from Gangwon, Chungbuk, and Gyeongbuk provinces, designated as KNUF-22-121A, KNUF-22-126A, and KNUF-22-316, respectively. Because the morphological and molecular analyses of these three strains were identical, KNUF-22-316 underwent further detailed study. Phylogenetic analyses based on the concatenated nucleotide sequences of the internal transcribed spacer region and the large subunit 28S rRNA gene revealed that the strain belonged to the genus Absidia, but occupied a distinct phylogenetic position. The strain KNUF-22-316 was compared with closely related species Absidia radiata CGMCC 3.16257T and Absidia yunnanensis CGMCC 3.16259T, morphologically different with shorter sporangiophores, smaller sporangia and columellae, and the consistent presence of collars. Here, we provide a detailed description and images of this proposed new species, which we have named Absidia microsporangia sp. nov.

12.
Radiographics ; 44(8): e230140, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38990775

RESUMO

Ectopic varices are rare but potentially life-threatening conditions usually resulting from a combination of global portal hypertension and local occlusive components. As imaging, innovative devices, and interventional radiologic techniques evolve and are more widely adopted, interventional radiology is becoming essential in the management of ectopic varices. The interventional radiologist starts by diagnosing the underlying causes of portal hypertension and evaluating the afferent and efferent veins of ectopic varices with CT. If decompensated portal hypertension is causing ectopic varices, placement of a transjugular intrahepatic portosystemic shunt is considered the first-line treatment, although this treatment alone may not be effective in managing ectopic variceal bleeding because it may not sufficiently resolve focal mesenteric venous obstruction causing ectopic varices. Therefore, additional variceal embolization should be considered after placement of a transjugular intrahepatic portosystemic shunt. Retrograde transvenous obliteration can serve as a definitive treatment when the efferent vein connected to the systemic vein is accessible. Antegrade transvenous obliteration is a vital component of interventional radiologic management of ectopic varices because ectopic varices often exhibit complex anatomy and commonly lack catheterizable portosystemic shunts. Superficial veins of the portal venous system such as recanalized umbilical veins may provide safe access for antegrade transvenous obliteration. Given the absence of consensus and guidelines, a multidisciplinary team approach is essential for the individualized management of ectopic varices. Interventional radiologists must be knowledgeable about the anatomy and hemodynamic characteristics of ectopic varices based on CT images and be prepared to consider appropriate options for each specific situation. ©RSNA, 2024 Supplemental material is available for this article.


Assuntos
Hemorragia Gastrointestinal , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/etiologia , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/terapia , Hipertensão Portal/diagnóstico por imagem , Hipertensão Portal/complicações , Varizes/diagnóstico por imagem , Varizes/terapia , Radiografia Intervencionista/métodos , Radiologia Intervencionista/métodos , Embolização Terapêutica/métodos , Tomografia Computadorizada por Raios X/métodos
13.
Proc Natl Acad Sci U S A ; 121(31): e2409232121, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39047044

RESUMO

Despite the availability of life-extending treatments for B cell leukemias and lymphomas, many of these cancers remain incurable. Thus, the development of new molecular targets and therapeutics is needed to expand treatment options. To identify new molecular targets, we used a forward genetic screen in mice to identify genes required for development or survival of lymphocytes. Here, we describe Zfp574, an essential gene encoding a zinc finger protein necessary for normal and malignant lymphocyte survival. We show that ZFP574 interacts with zinc finger protein THAP12 and promotes the G1-to-S-phase transition during cell cycle progression. Mutation of ZFP574 impairs nuclear localization of the ZFP574-THAP12 complex. ZFP574 or THAP12 deficiency results in cell cycle arrest and impaired lymphoproliferation. Germline mutation, acute gene deletion, or targeted degradation of ZFP574 suppressed Myc-driven B cell leukemia in mice, but normal B cells were largely spared, permitting long-term survival, whereas complete lethality was observed in control animals. Our findings support the identification of drugs targeting ZFP574-THAP12 as a unique strategy to treat B cell malignancies.


Assuntos
Linfócitos B , Animais , Camundongos , Linfócitos B/metabolismo , Leucemia de Células B/genética , Leucemia de Células B/patologia , Leucemia de Células B/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Camundongos Endogâmicos C57BL , Linfoma de Células B/genética , Linfoma de Células B/patologia , Linfoma de Células B/metabolismo
14.
Nat Commun ; 15(1): 5117, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879551

RESUMO

Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Oxigênio , Microambiente Tumoral , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Animais , Camundongos , Oxigênio/metabolismo , Linhagem Celular Tumoral , Masculino , Feminino , Ensaios Antitumorais Modelo de Xenoenxerto , Pessoa de Meia-Idade , Dispositivos Lab-On-A-Chip
15.
J Hum Genet ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824232

RESUMO

INTRODUCTION: Kabuki syndrome (KS) is a rare disorder characterized by typical facial features, skeletal anomalies, fetal fingertip pad persistence, postnatal growth retardation, and intellectual disabilities. Heterozygous variants of the KMT2D and KDM6A genes are major genetic causes of KS. This study aimed to report the clinical and genetic characteristics of KS. METHODS: This study included 28 Korean patients (14 boys and 14 girls) with KS through molecular genetic testing, including direct Sanger sequencing, whole-exome sequencing, or whole-genome sequencing. RESULTS: The median age at clinical diagnosis was 18.5 months (IQR 7-58 months), and the median follow-up duration was 80.5 months (IQR 48-112 months). Molecular genetic testing identified different pathogenic variants of the KMT2D (n = 23) and KDM6A (n = 3) genes, including 15 novel variants. Patients showed typical facial features (100%), such as long palpebral fissure and eversion of the lower eyelid; intellectual disability/developmental delay (96%); short stature (79%); and congenital cardiac anomalies (75%). Although 71% experienced failure to thrive in infancy, 54% of patients showed a tendency toward overweight/obesity in early childhood. Patients with KDM6A variants demonstrated severe genotype-phenotype correlation. CONCLUSION: This study enhances the understanding of the clinical and genetic characteristics of KS.

16.
Can Vet J ; 65(6): 553-558, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827592

RESUMO

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.


Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).


Assuntos
Antineoplásicos , Doenças do Cão , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib , Animais , Tumores do Estroma Gastrointestinal/veterinária , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Cães , Mesilato de Imatinib/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Feminino , Antineoplásicos/uso terapêutico , Trifosfato de Adenosina/uso terapêutico , Indóis , Pirróis
18.
BMC Palliat Care ; 23(1): 160, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918773

RESUMO

BACKGROUND: This study aimed to investigate the trends of aggressive care at the end-of-life (EoL) for patients with advanced cancer in Korea and to identify factors affecting such care analyzing nationwide data between 2012 to 2018. METHODS: This was a population-based, retrospective nationwide study. We used administrative data from the National Health Insurance Service and the Korea Central Cancer Registry to analyze 125,350 patients aged 20 years and above who died within one year of a stage IV cancer diagnosis between 2012 and 2018. RESULTS: The overall aggressiveness of EoL care decreased between 2012 and 2018. In patients' last month of life, chemotherapy use (37.1% to 32.3%; p < 0.05), cardiopulmonary resuscitation (13.2% to 10.4%; p < 0.05), and intensive care unit admission (15.2% to 11.1%; p < 0.05) decreased during the study period, although no significant trend was noted in the number of emergency room visits. A steep increase was seen in inpatient hospice use in the last month of life (8.6% to 26.6%; p < 0.05), while downward trends were observed for hospice admission within three days prior to death (13.9% to 11%; p < 0.05). Patients were more likely to receive aggressive EoL care if they were younger, women, had treatment in tertiary hospitals, or had hematologic malignancies. In the subgroup analysis, the overall trend of aggressive EoL care decreased for all five major cancer types. CONCLUSION: The aggressiveness of EoL care in stage IV cancer patients showed an overall decrease during 2012-2018 in Korea.


Assuntos
Neoplasias , Assistência Terminal , Humanos , República da Coreia , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Neoplasias/mortalidade , Estudos Retrospectivos , Idoso , Assistência Terminal/métodos , Assistência Terminal/estatística & dados numéricos , Assistência Terminal/tendências , Adulto , Idoso de 80 Anos ou mais , Sistema de Registros/estatística & dados numéricos
19.
Int J Biol Macromol ; 272(Pt 2): 132903, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38848840

RESUMO

Fenofibrate (FNF) is used to treat hyperlipidemia. However, FNF is a poorly water-soluble drug, and the dosage of commercial products is relatively high at 160 mg in a Lipidil® tablet. Therefore, this study aimed to develop an FNF-solid dispersion (SD) that solubilizes and stabilizes FNF. The melting method that uses the low melting point of FNF was employed. The dissolution percentage of FNF in the optimal formulation (SD2) increased by 1.2-, 1.3-, and 1.3-fold at 5 min compared to that of Lipidil® and increased by 2.0-, 2.1-, and 2.0-fold compared to the pure FNF in pH 1.2 media, distilled water, and pH 6.8 buffer, which included 0.025 M sodium lauryl sulfate, respectively. The SD2 formulation showed a dissolution percentage of nearly 100 % in all dissolution media after 60 min. The physicochemical properties of the SD2 formulation exhibited slight changes in the melting point and crystallinity of FNF. Moreover, the stability of the SD2 formulation was maintained for six months. In particular, it was challenging to secure stability when starch#1500 was excluded from the SD2 formulation. In conclusion, the dissolution percentage of FNF in the SD2 formulation was improved owing to the weak binding force between FNF and the excipients, stability was secured, and favorable results are expected in future animal experiments.


Assuntos
Fenofibrato , Solubilidade , Amido , Fenofibrato/química , Amido/química , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Temperatura de Transição , Química Farmacêutica/métodos , Concentração de Íons de Hidrogênio , Hipolipemiantes/química
20.
J Am Heart Assoc ; 13(13): e034055, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38904229

RESUMO

BACKGROUND: Although peripartum cardiomyopathy (PPCM) is a fatal disease affecting young patients and fetuses, little is known about its recent prognosis and risk factors. This study investigated temporal trends in clinical characteristics and outcomes for PPCM in a nationwide multicenter registry. METHODS AND RESULTS: The study population comprised 340 patients (mean age, 33 years) who were diagnosed with PPCM between January 2000 and September 2022 in 26 tertiary hospitals in South Korea. PPCM was defined as heart failure with left ventricular ejection fraction ≤45% and no previously known cardiac disease. The main study outcomes included time to the first occurrence of all-cause death, heart transplantation, and cardiovascular hospitalization. The diagnosis of PPCM cases increased notably during the study period (P<0.001). However, clinical outcomes showed no significant improvement (all-cause death for 10 years: 0.9% [2000-2010] versus 2.3% [2011-2022], P=0.450; all-cause death and heart transplantation for 10 years: 3.6% [2000-2010] versus 3.0% [2011-2022] P=0.520; all-cause death, heart transplantation, and cardiovascular hospitalization for 10 years: 11.7% [2000-2010] versus 19.8% [2011-2022], P=0.240). High body mass index (hazard ratio [HR], 1.106 [95% CI, 1.024-1.196]; P=0.011), the presence of gestational diabetes (HR, 5.346 [95% CI, 1.778-16.07]; P=0.002), and increased baseline left ventricular end-diastolic dimension (HR, 1.078 [95% CI, 1.002-1.159]; P=0.044) were significant risk factors for poor prognosis. CONCLUSIONS: While the incidence of PPCM has increased over the past 20 years, the prognosis has not improved significantly. Timely management and close follow-up are necessary for high-risk patients with PPCM with high body mass index, gestational diabetes, or large left ventricular end-diastolic dimension.


Assuntos
Cardiomiopatias , Período Periparto , Complicações Cardiovasculares na Gravidez , Sistema de Registros , Humanos , Feminino , Adulto , Gravidez , República da Coreia/epidemiologia , Cardiomiopatias/epidemiologia , Cardiomiopatias/terapia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/mortalidade , Complicações Cardiovasculares na Gravidez/epidemiologia , Complicações Cardiovasculares na Gravidez/terapia , Fatores de Risco , Fatores de Tempo , Transplante de Coração/tendências , Transplante de Coração/estatística & dados numéricos , Prognóstico , Função Ventricular Esquerda , Volume Sistólico , Causas de Morte/tendências , Hospitalização/tendências , Hospitalização/estatística & dados numéricos , Transtornos Puerperais/epidemiologia , Transtornos Puerperais/terapia , Transtornos Puerperais/mortalidade , Transtornos Puerperais/fisiopatologia , Estudos Retrospectivos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Incidência
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