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1.
Biol Pharm Bull ; 47(10): 1682-1689, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39443086

RESUMEN

Although multimodality therapy has recently advanced, patients with glioblastoma, one of the most aggressive and deadly types of central nervous system cancer, have a very poor prognosis and rare long-term survival. Vitamins are essential organic nutrients that play a pivotal role in maintaining homeostasis, and various studies have demonstrated the implication of vitamins in the pathophysiology of gliomas. Herein, we aimed to investigate the association of the vitamin metabolic pathway and the corresponding candidate genes for the malignancy, aggressiveness, and poor prognosis of gliomas using The Cancer Genome Atlas database of patients with gliomas. We demonstrated that fat-soluble vitamin metabolic processes are prominently associated with glioma grade, molecular biomarkers, molecular subtypes, and clinical outcomes. Moreover, we identified the key genes related to the fat-soluble metabolic pathway in gliomas using differentially expressed gene analysis. Among them, the expression of the vitamin K epoxide reductase complex subunit 1 (VKORC1), encoding VKOR essential for the vitamin K-dependent γ-carboxylation of target proteins, was prominently associated with not only malignancy, aggressiveness, and poor prognosis of gliomas but also the representative signal pathways related to glioma pathogenesis. Moreover, the inactivation of Vkorc1 by RNA interference decreased the proliferation and migration potential of glioma cells in vitro. Collectively, these findings reveal the pivotal role of fat-soluble vitamin and vitamin K metabolic processes in the pathophysiology of gliomas, thereby identifying a potential target for drug development for the treatment of malignant gliomas.


Asunto(s)
Neoplasias Encefálicas , Glioma , Vitaminas , Humanos , Glioma/metabolismo , Glioma/patología , Glioma/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Vitaminas/uso terapéutico , Línea Celular Tumoral , Progresión de la Enfermedad , Proliferación Celular , Movimiento Celular , Vitamina K/metabolismo , Pronóstico
2.
Cureus ; 16(8): e67797, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39328716

RESUMEN

Introduction Myocardial properties can be quantitatively evaluated using myocardial native T1 values (nT1) obtained using cardiac magnetic resonance imaging (CMR). In terms of myocardial wall thickness, the left ventricular nT1 is easy to measure, but the right ventricular nT1 is difficult. Patients with congenital heart disease often develop right ventricular overload. If right ventricular nT1 can be measured consistently, inflammation and fibrosis of the right ventricular myocardium can be quantitatively evaluated. We aimed to determine whether T1 mapping during systole can be used to evaluate right ventricular myocardial properties. Methods T1 mapping was performed at diastole and systole. Systolic T1 mapping was calculated from diastolic T1 mapping and cine images. The myocardial properties of both ventricles were evaluated in 13 healthy volunteers (21-26 years old) and 12 patients with right ventricular overload (12-41 years old) who underwent CMR examination at our hospital. Results From the analysis of left ventricular nT1, we found that nT1 did not change significantly during the cardiac cycle. However, right ventricular nT1 changed between diastole and systole because the right ventricle is affected by blood. Although there was no difference in right ventricular diastolic nT1 between the patients and volunteers (1,346.8 vs. 1,347.6 ms, p = 0.852), the right ventricular systolic nT1 was significantly higher in patients than in volunteers (1,312.7 vs. 1,233.8 ms, p = 0.002). This indicates that right ventricular myocardial damage occurs in patients with right ventricular overload. Conclusion Systolic right ventricular myocardial T1 mapping allows assessment of right ventricular myocardial properties. The right ventricular myocardial systolic nT1 is useful for evaluating myocardial damage due to right ventricular stress and myocardial injury. Measuring right ventricular nT1 may allow consideration of early therapeutic intervention.

3.
Nutrients ; 16(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38999857

RESUMEN

Dietary and physical activity interventions through smartphone healthcare applications (apps) have recently surged in popularity as effective methods for weight loss. However, the specific factors contributing to successful weight loss remain uncertain. We conducted an analysis of baseline characteristics and app usage frequencies over three months among 68 Japanese adults with overweight and obesity who were assigned to the intervention group in a previous randomized controlled trial. Logistic regression analysis revealed a negative association (OR: 0.248; p = 0.018) between having a walking habit at baseline and successful weight loss, defined as a 3% reduction in initial weight. Additionally, slower walking speeds and family medical history were identified as potential predictors of successful weight loss. These findings offer insights into the profile of individuals who achieve success in weight loss through our smartphone app, providing valuable guidance for the development of future healthcare apps.


Asunto(s)
Aplicaciones Móviles , Obesidad , Sobrepeso , Teléfono Inteligente , Pérdida de Peso , Humanos , Femenino , Masculino , Persona de Mediana Edad , Obesidad/terapia , Adulto , Sobrepeso/terapia , Programas de Reducción de Peso/métodos , Caminata , Ejercicio Físico , Japón , Resultado del Tratamiento
4.
J Clin Exp Hematop ; 64(2): 107-118, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38925972

RESUMEN

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.


Asunto(s)
Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/mortalidad , Adulto , Estudios Retrospectivos , Pronóstico , Trasplante de Células Madre Hematopoyéticas , Receptores Quiméricos de Antígenos , Recurrencia
5.
Egypt Heart J ; 76(1): 53, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696068

RESUMEN

BACKGROUND: Four-dimensional flow magnetic resonance imaging (MRI) enables blood flow visualization. The absence of left atrial vortex flow (LAVF) has been implicated in the development of thrombus formation and arrhythmias. However, the clinical relevance of this phenomenon in patients with congenital heart disease (CHD) remains unclear. This study aimed to unravel the relationship of LAVF with left atrial functions in patients with CHD. RESULTS: Twenty-five participants who underwent cardiac MRI examinations were included (8 postoperative patients with CHD aged 17-41 years and 17 volunteers aged 21-31 years). All participants were in sinus rhythm. Four-dimensional flow MRI (velocity encoding 100 cm/s) assessed the presence of LAVF, and its relationship with left atrial function determined by transthoracic echocardiography was explored. LAVF was detected in 16 patients. Upon classification of the participants based on the presence or absence of LAVF, 94% of participants in the LAVF group were volunteers, while 78% of those in the without LAVF group were postoperative patients. Participants without LAVF had a significantly lower left atrial ejection fraction (61% vs. 70%, p = 0.019), reservoir (32% vs. 47%, p = 0.006), and conduit (22% vs. 36%, p = 0.002) function than those with LAVF. CONCLUSIONS: LAVF occurred during the late phase of ventricular systole, and left atrial reservoir function may have contributed to its occurrence. Many postoperative patients with CHD experienced a loss of LAVF. LAVF may indicate early left atrial dysfunction resulting from left atrial remodeling.

6.
J Clin Med ; 13(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38673643

RESUMEN

Background: Treatment of oropharyngolaryngeal venous malformations (VMs) remains challenging. This study evaluated the effectiveness and safety of fluoroscopy- and endoscopy-guided transoral sclerotherapy for oropharyngolaryngeal VMs in a hybrid operation room (OR). Methods: Patients with oropharyngolaryngeal VMs who underwent transoral sclerotherapy in a hybrid OR were enrolled. Results: Fourteen patients (six females, eight males; median age of 26 years; range, 4-71 years) were analyzed. The symptoms observed were breathing difficulties (n = 3), snoring (n = 2), sleep apnea (n = 1), and swallowing difficulties (n = 1). Lesions were extensive in the face and neck (n = 9) and limited in the oropharyngolarynx (n = 5). A permanent tracheostomy was performed on two patients, while a temporary tracheostomy was performed on five patients. The treated regions were the soft palate (n = 8), pharynx (n = 7), base of the tongue (n = 4), and epiglottis (n = 1). The median number of sclerotherapy sessions was 2.5 (range, 1-9). The median follow-up duration was 81 months (range, 6-141). Treatment outcomes were graded as excellent (n = 2), good (n = 7), or fair (n = 5). The post-treatment complication was bleeding (n = 1), resulting in an urgent tracheostomy. Conclusions: Fluoroscopy- and endoscopy-guided transoral sclerotherapy in a hybrid OR can be effective and safe for oropharyngolaryngeal VMs.

7.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167074, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38354758

RESUMEN

For the advancement of DKD treatment, identifying unrecognized residual risk factors is essential. We explored the impact of obesity diversity derived from different carbohydrate qualities, with an emphasis on the increasing trend of excessive fructose consumption and its effect on DKD progression. In this study, we utilized db/db mice to establish a novel diabetic model characterized by fructose overconsumption, aiming to uncover the underlying mechanisms of renal damage. Compared to the control diet group, the fructose-fed db/db mice exhibited more pronounced obesity yet demonstrated milder glucose intolerance. Plasma cystatin C levels were elevated in the fructose model compared to the control, and this elevation was accompanied by enhanced glomerular sclerosis, even though albuminuria levels and tubular lesions were comparable. Single-cell RNA sequencing of the whole kidney highlighted an increase in Lrg1 in glomerular endothelial cells (GECs) in the fructose model, which appeared to drive mesangial fibrosis through enhanced TGF-ß1 signaling. Our findings suggest that excessive fructose intake exacerbates diabetic kidney disease progression, mediated by aberrant Lrg1-driven crosstalk between GECs and mesangial cells.


Asunto(s)
Nefropatías Diabéticas , Células Mesangiales , Ratones , Animales , Células Endoteliales/patología , Fructosa/efectos adversos , Nefropatías Diabéticas/patología , Ratones Endogámicos , Obesidad/complicaciones , Comunicación Celular
8.
Radiother Oncol ; 193: 110121, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38311031

RESUMEN

INTRODUCTION: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. MATERIALS AND METHODS: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. RESULTS: Median age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). CONCLUSION: This study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Terapia de Protones , Humanos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Terapia de Protones/efectos adversos , Quimioterapia Adyuvante , Neoplasias Pulmonares/patología , Inmunoterapia/efectos adversos , Estudios Retrospectivos
9.
Biochem Biophys Rep ; 37: 101607, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38178924

RESUMEN

Renal artery stenosis-induced chronic renal ischemia is an important cause of renal dysfunction, especially in older adults, and its incidence is currently increasing. To elucidate the mechanisms underlying chronic renal hypoperfusion-induced kidney damage, we developed a novel mouse model of renal artery coiling-based chronic hypoperfusion-related kidney injury. This model exhibits decreased renal blood flow and function, atrophy, and parenchymal injury in the coiled kidney, along with compensatory hypertrophy in the non-coiled kidney, without chronic hypertension. The availability of this mouse model, which can develop renal ischemia without genetic modification, will enhance kidney disease research by serving as a new tool to investigate the effects of acquired factors (e.g., obesity and aging) and genetic factors on renal artery stenosis-related renal parenchymal damage.

10.
Heart Vessels ; 39(2): 117-122, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37740077

RESUMEN

Left atrial (LA) stiffness is one of the most important factors involved in LA remodeling. LA stiffness has rarely been studied postoperatively in patients with congenital heart diseases (CHDs). This study aimed to evaluate LA stiffness in CHD patients postoperatively. Seventy-five patients (CHDs, 67; controls, 8; age range, 10-41 years) who underwent cardiac catheterization at our institution were included in this study. From the pulmonary artery wedge pressure waveform obtained during cardiac catheterization, the pressure range between the v wave and x trough was determined, and this value was divided by the LA reservoir strain obtained by echocardiography to calculate LA stiffness, as previously reported. LA stiffness was significantly higher in postoperative CHD patients than in controls (0.28 ± 0.17 vs. 0.13 ± 0.03, p = 0.001). Nineteen of 52 (37%) patients in their teens, 8 of 11 (73%) patients in their 20 s, and 1 of 4 (25%) patients aged > 30 years had elevated LA stiffness values. In particular, all patients with an LA reservoir strain < 20% had elevated LA stiffness. In postoperative CHD patients, LA stiffness was frequently elevated from a young age. CHD patients with elevated LA stiffness should be cautious of possible LA dysfunction in the future.


Asunto(s)
Apéndice Atrial , Cardiopatías Congénitas , Adolescente , Humanos , Niño , Adulto Joven , Adulto , Atrios Cardíacos/diagnóstico por imagen , Ecocardiografía , Cateterismo Cardíaco , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/cirugía
11.
Microscopy (Oxf) ; 73(2): 154-168, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-37698551

RESUMEN

Herein, we review notable points from observations of electrochemical reactions in a liquid electrolyte by liquid-phase electron microscopy. In situ microscopic observations of electrochemical reactions are urgently required, particularly to solve various battery issues. Battery performance is evaluated by various electrochemical measurements of bulk samples. However, it is necessary to understand the physical/chemical phenomena occurring in batteries to elucidate the reaction mechanisms. Thus, in situ microscopic observation is effective for understanding the reactions that occur in batteries. Herein, we focus on two methods, of the liquid phase (scanning) transmission electron microscopy and liquid phase scanning electron microscopy, and summarize the advantages and disadvantages of both methods.

12.
Radiother Oncol ; 191: 110061, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38122850

RESUMEN

PURPOSE: Accurate and comprehensive segmentation of cardiac substructures is crucial for minimizing the risk of radiation-induced heart disease in lung cancer radiotherapy. We sought to develop and validate deep learning-based auto-segmentation models for cardiac substructures. MATERIALS AND METHODS: Nineteen cardiac substructures (whole heart, 4 heart chambers, 6 great vessels, 4 valves, and 4 coronary arteries) in 100 patients treated for non-small cell lung cancer were manually delineated by two radiation oncologists. The valves and coronary arteries were delineated as planning risk volumes. An nnU-Net auto-segmentation model was trained, validated, and tested on this dataset with a split ratio of 75:5:20. The auto-segmented contours were evaluated by comparing them with manually drawn contours in terms of Dice similarity coefficient (DSC) and dose metrics extracted from clinical plans. An independent dataset of 42 patients was used for subjective evaluation of the auto-segmentation model by 4 physicians. RESULTS: The average DSCs were 0.95 (+/- 0.01) for the whole heart, 0.91 (+/- 0.02) for 4 chambers, 0.86 (+/- 0.09) for 6 great vessels, 0.81 (+/- 0.09) for 4 valves, and 0.60 (+/- 0.14) for 4 coronary arteries. The average absolute errors in mean/max doses to all substructures were 1.04 (+/- 1.99) Gy and 2.20 (+/- 4.37) Gy. The subjective evaluation revealed that 94% of the auto-segmented contours were clinically acceptable. CONCLUSION: We demonstrated the effectiveness of our nnU-Net model for delineating cardiac substructures, including coronary arteries. Our results indicate that this model has promise for studies regarding radiation dose to cardiac substructures.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Aprendizaje Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Corazón/diagnóstico por imagen , Órganos en Riesgo
13.
Microbiome Res Rep ; 2(2): 12, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38047276

RESUMEN

Aim: Dietary plant fibers affect gut microbiota composition; however, the underlying microbial degradation pathways are not fully understood. We previously discovered 3-O-α-D-galactosyl-α-L-arabinofuranosidase (GAfase), a glycoside hydrolase family 39 enzyme involved in the assimilation of side chains of arabinogalactan protein (AGP), from Bifidobacterium longum subsp. longum (B. longum) JCM7052. Although GAfase homologs are not highly prevalent in the Bifidobacterium genus, several Bifidobacterium strains possess the homologs. To explore the differences in substrate specificity among the homologs, a homolog of B. longum GAfase in Bifidobacterium pseudocatenulatum MCC10289 (MCC10289_0425) was characterized. Methods: Gum arabic, larch, wheat AGP, and sugar beet arabinan were used to determine the substrate specificity of the MCC10289_0425 protein. An amino acid replacement was introduced into GAfase to identify a critical residue that governs the differentiation of substrate specificity. The growth of several Bifidobacterium strains on ß-L-arabinopyranosyl disaccharide and larch AGP was examined. Results: MCC10289_0425 was identified to be an unprecedented 3-O-ß-L-arabinopyranosyl-α-L-arabinofuranosidase (AAfase) with low GAfase activity. A single amino acid replacement (Asn119 to Tyr) at the catalytic site converted GAfase into AAfase. AAfase releases sugar source from AGP, thereby allowing B. pseudocatenulatum growth. Conclusion: Bifidobacteria have evolved several homologous enzymes with overlapping but distinct substrate specificities depending on the species. They have acquired different fitness abilities to respond to diverse plant polysaccharide structures.

14.
Clin Case Rep ; 11(12): e8161, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38125623

RESUMEN

We present a case of spontaneous cervical chyle leak that showed as left-sided neck swelling. Spontaneous chyle leak is extremely rare. Lymphangiography with lipiodol is useful as a diagnostic and therapeutic approach for chyle leak.

15.
JMIR Form Res ; 7: e48435, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37938885

RESUMEN

BACKGROUND: Self-tracking smartphone apps have emerged as promising tools to encourage healthy behaviors. In this longitudinal study, we used gym use data from members of a major fitness club that operates gyms throughout Japan from January 2014 to December 2019. OBJECTIVE: Our objective was to assess the extent to which a health and fitness self-tracking mobile app introduced to gym members on January 1, 2018, contributed to their weight loss. The app allows users to input information regarding diet, sleep, weight, and gym exercise so that they can receive personalized feedback from an artificial intelligence chatbot to improve their health behaviors. METHODS: We used linear regression to quantify the association between app use and weight loss. The primary outcome of the study was the weight loss achieved by each gym user, which was calculated as the difference between their initial and final weights in kilograms, as recorded in the app. Individuals who did not attend the gym or failed to use the mobile app at least twice during the study period were excluded from the analysis. The model accounted for age, gender, distance between the gym and the member's residence, average weekly number of times a member used the gym, user's gym membership length in weeks, average weekly number of times a member input information into the app, and the number of weeks that the app was used at least once. RESULTS: Data from 26,589 participants were analyzed. Statistically significant associations were detected between weight loss and 2 metrics related to app use: the average weekly frequency of use and the total number of weeks in which the app was used at least once. One input per week was found to be associated with a loss of 62.1 (95% CI 53.8-70.5) g, and 1 week of app use was associated with 21.7 (95% CI 20.5-22.9) g of weight loss from the day of the first input to that of the final input to the app. Furthermore, the average number of times that a member used the gym weekly was also shown to be statistically significantly associated with weight loss: 1 use per week was associated with 255.5 (95% CI 228.5-282.6) g of weight loss. CONCLUSIONS: This empirical study demonstrated a significant association between weight loss among gym members and not only the frequency of weekly gym use but also the use of a health and fitness self-tracking app. However, further work is needed to examine the mechanisms through which mobile apps affect health behaviors and to identify the specific app features that are most effective in promoting weight loss.

16.
Clin Case Rep ; 11(10): e7941, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37854254

RESUMEN

We present a case of partially involuting congenital hemangioma (PICH) that showed rapid growth with ulceration after incisional biopsy. PICH does not typically grow after birth. However, if growth occurs due to stimuli like biopsy, it is essential to consider the possibility of pyogenic granuloma complication.

17.
Brachytherapy ; 22(6): 697-708, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37690972

RESUMEN

α-particle targeted radionuclide therapy has shown promise for optimal cancer management, an exciting new era for brachytherapy. Alpha-emitting nuclides can have significant advantages over gamma- and beta-emitters due to their high linear energy transfer (LET). While their limited path length results in more specific tumor 0kill with less damage to surrounding normal tissues, their high LET can produce substantially more lethal double strand DNA breaks per radiation track than beta particles. Over the last decade, the physical and chemical attributes of Actinium-225 (225Ac) including its half-life, decay schemes, path length, and straightforward chelation ability has peaked interest for brachytherapy agent development. However, this has been met with challenges including source availability, accurate modeling for standardized dosimetry for brachytherapy treatment planning, and laboratory space allocation in the hospital setting for on-demand radiopharmaceuticals production. Current evidence suggests that a simple empirical approach based on 225Ac administered radioactivity may lead to inconsistent outcomes and toxicity. In this review article, we highlight the recent advances in 225Ac source production, dosimetry modeling, and current clinical studies.


Asunto(s)
Braquiterapia , Neoplasias , Humanos , Braquiterapia/métodos , Neoplasias/radioterapia , Radiofármacos/uso terapéutico , Actinio/uso terapéutico
18.
Orphanet J Rare Dis ; 18(1): 270, 2023 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-37667289

RESUMEN

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS. RESULTS: Participants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5-57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3-7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6-17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype-phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1. CONCLUSIONS: The PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.


Asunto(s)
Síndrome de Klippel-Trenaunay-Weber , Femenino , Humanos , Masculino , Fosfatidilinositol 3-Quinasa Clase I/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Síndrome de Klippel-Trenaunay-Weber/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Serina-Treonina Quinasas TOR , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad
19.
Int J Surg ; 109(12): 4119-4125, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37720948

RESUMEN

BACKGROUND: Several large-scale studies have assessed endovascular and surgical treatment methods for nonocclusive mesenteric ischemia (NOMI); however, the prognostic factors for NOMI remain unclear. Therefore, this study aimed to evaluate risk factors for in-hospital mortality among patients with NOMI who underwent laparotomy and to examine therapeutic strategies that may improve the prognosis. MATERIALS AND METHODS: In this multicenter retrospective study, the authors reviewed the electronic medical records retrieved from the inpatient database of patients with NOMI at eight district general hospitals between January 2011 and January 2021. A total of 88 patients who underwent laparotomies were divided into survivor and nonsurvivor groups, and statistical analysis was performed to determine clinical and physiological factors. RESULTS: Exploratory laparotomy based on second-look surgery was the first treatment choice. The overall mortality rate was 48.8%, with a male-to-female ratio of 1.1:1. The median Sequential Organ Failure Assessment (SOFA) score was 8 [interquartile range: 3.75-14.2], and the median SOFA scores were 5 [3-7] in the survivor group and 13 [9-17.5] in the nonsurvivor group. Univariate analysis revealed a significant difference in BMI ( P <0.001), hypoglycemia ( P =0.0012), previous cardiovascular surgery ( P =0.0019), catecholamine use ( P <0.001), SOFA score ( P <0.001), platelet count ( P =0.0023), and lactate level ( P <0.001). Logistic regression analysis using the factors with significant differences revealed that SOFA score ≥10 (odds ratio 23.3; 95% CI: 1.94-280.00; P =0.013) was an independent prognostic factor. In addition, catecholamine use was suggested as a factor with a SOFA score greater than or equal to 10. CONCLUSION: This study confirmed that a SOFA score of greater than or equal to 10 may be associated with increased mortality. While closely monitoring low blood pressure and renal dysfunction, survival rates may be improved if surgical intervention is performed before the SOFA score reaches greater than or equal to 10.


Asunto(s)
Isquemia Mesentérica , Puntuaciones en la Disfunción de Órganos , Humanos , Masculino , Femenino , Pronóstico , Estudios Retrospectivos , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/cirugía , Catecolaminas
20.
Rinsho Ketsueki ; 64(7): 586-595, 2023.
Artículo en Japonés | MEDLINE | ID: mdl-37544717

RESUMEN

Pola-BR (polatuzumab vedotin, bendamustine, and rituximab) therapy received approval for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in Japan in March 2021. There have been few reports on the efficacy and safety of Pola-BR therapy in Japanese clinical practice. A retrospective analysis was performed on twenty-nine patients with R/R DLBCL who received Pola-BR therapy at our institution (intent to cellular immunotherapy cohort: 20 patients, stand-alone treatment cohort: nine patients). The overall response rate was 69.0% (complete response 27.6%). The median progression-free survival was 5.1 months, with a 9.5-month median overall survival. In the intent to cellular immunotherapy cohort, 11 of 19 patients received chimeric antigen receptor T-cell (CAR-T) infusions, and one patient received allogeneic stem cell transplantation. Four patients received Pola-BR therapy, including bendamustine before leukapheresis, and all produced CAR-T products successfully. 3 of the 28 patients experienced grade3 or higher adverse events, and two required treatment discontinuation. Our single institution, a real-world cohort of R/R DLBCL patients showed high efficacy outcomes and a tolerable toxicity profile for Pola-BR therapy, which is comparable to previous studies. More cases are needed to determine its impact on CAR-T therapy and stem cell transplantation.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunoconjugados , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/uso terapéutico , Tratamiento Basado en Trasplante de Células y Tejidos , Inmunoconjugados/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Receptores Quiméricos de Antígenos/uso terapéutico , Estudios Retrospectivos , Rituximab/uso terapéutico
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