RESUMEN
The coupling of light to electrical charge carriers in semiconductors is the foundation of many technological applications. Attosecond transient absorption spectroscopy measures simultaneously how excited electrons and the vacancies they leave behind dynamically react to the applied optical fields. In compound semiconductors, these dynamics can be probed via any of their atomic constituents with core-level transitions into valence and conduction band. Typically, the atomic species forming the compound contribute comparably to the relevant electronic properties of the material. One therefore expects to observe similar dynamics, irrespective of the choice of atomic species via which it is probed. Here, we show in the two-dimensional transition metal dichalcogenide semiconductor MoSe2, that through a selenium-based core-level transition we observe charge carriers acting independently from each other, while when probed through molybdenum, the collective, many-body motion of the carriers dominates. Such unexpectedly contrasting behavior can be explained by a strong localization of electrons around molybdenum atoms following absorption of light, which modifies the local fields acting on the carriers. We show that similar behavior in elemental titanium metal [M. Volkov et al., Nat. Phys. 15, 1145-1149 (2019)] carries over to transition metal-containing compounds and is expected to play an essential role for a wide range of such materials. Knowledge of independent particle and collective response is essential for fully understanding these materials.
RESUMEN
BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Receptor ErbB-3 , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Femenino , Receptor ErbB-3/genética , Receptor ErbB-3/antagonistas & inhibidores , Persona de Mediana Edad , Masculino , Anciano , Adulto , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anciano de 80 o más Años , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos ampliamente neutralizantes , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Inmunoconjugados/administración & dosificaciónRESUMEN
The side chain dynamics of poly(quinoxaline-2,3-diyl)s (PQXs) are expected to influence their conformation. To investigate these dynamics experimentally, quasielastic neutron scattering (QENS) was performed for PQXs in deuterated tetrahydrofuran (THF-d8) and deuterated 1,1,2-trichloroethane/THF (1,1,2-TCE-d3/THF-d8), in which they formed right-handed and left-handed helical structures, respectively. The mean-square displacement of the PQX side chains in 1,1,2-TCE-d3/THF-d8 was lower than that in THF-d8. Furthermore, QENS complementary studies and molecular dynamics simulations unraveled a coupling between the main-chain and side chain dynamics of PQXs, suggesting the possibility of controlling the main-chain helical chirality through the dynamics of chiral side chains. These insights present a novel strategy for the design of synthetic helical macromolecules with precise chirality control.
RESUMEN
BACKGROUND: Although functional end-to-end anastomosis (FEEA) using a stapler in the colorectal field has been recognised worldwide, the technique varies by surgeon, and the safety of anastomosis using different techniques is unknown. METHODS: This multicentre prospective observational cohort study was conducted by the KYCC Study Group in Yokohama, Japan, and included patients who underwent colonic resection at seven centres between April 2020 and March 2022. This study compared the incidence of surgery-related abdominal complications (SAC: anastomotic leakage [AL], anastomotic bleeding, intra-abdominal abscess, enteritis, ileus, surgical site infection, and other abdominal complications) between two different methods of FEEA (one-step [OS] method: simultaneous anastomosis and bowel resection; two-step [TS] method: anastomosis after bowel resection). Complications of Clavien-Dindo classification grade 2 or higher were assessed. RESULTS: Among 293 eligible cases, the OS and TS methods were used in 194 (66.2%) and 99 (33.8%) patients, respectively. The baseline characteristics were similar between the groups. The OS method used fewer staplers (three vs. four staplers, p < 0.00001). There were no significant differences in SAC rate between the OS (19.1%) and the TS (16.2%) groups (p = 0.44). The OS group had four cases (2.1%) of AL (two patients; grade 3, two patients; grade 2) while the TS group had one case (1.0%) of grade 2 AL (p = 0.67). Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 3.95; p < 0.00001), an open surgical approach (OR 2.36; p = 0.03), and longer operative duration (OR,2.79; p = 0.002) were independent predictors of complications, whereas the OS method was not an independent predictor (OR 1.17; p = 0.66). CONCLUSIONS: The OS and the TS technique for stapled colonic anastomosis in a FEEA had a similar postoperative complication rate. TRIAL REGISTRATION NUMBER: UMIN000039902 (registration date 23 March 2020).
Asunto(s)
Anastomosis Quirúrgica , Colectomía , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Anastomosis Quirúrgica/métodos , Anastomosis Quirúrgica/efectos adversos , Estudios Prospectivos , Anciano , Japón , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Colectomía/métodos , Colectomía/efectos adversos , Colon/cirugía , Fuga Anastomótica/etiología , Fuga Anastomótica/epidemiología , Incidencia , Anciano de 80 o más Años , Grapado Quirúrgico/métodos , Pueblos del Este de AsiaRESUMEN
Electric-field-induced charge separation (polarization) is the most fundamental manifestation of the interaction of light with matter and a phenomenon of great technological relevance. Nonlinear optical polarization produces coherent radiation in spectral ranges inaccessible by lasers and constitutes the key to ultimate-speed signal manipulation. Terahertz techniques have provided experimental access to this important observable up to frequencies of several terahertz. Here we demonstrate that attosecond metrology extends the resolution to petahertz frequencies of visible light. Attosecond polarization spectroscopy allows measurement of the response of the electronic system of silica to strong (more than one volt per ångström) few-cycle optical (about 750 nanometres) fields. Our proof-of-concept study provides time-resolved insight into the attosecond nonlinear polarization and the light-matter energy transfer dynamics behind the optical Kerr effect and multi-photon absorption. Timing the nonlinear polarization relative to the driving laser electric field with sub-30-attosecond accuracy yields direct quantitative access to both the reversible and irreversible energy exchange between visible-infrared light and electrons. Quantitative determination of dissipation within a signal manipulation cycle of only a few femtoseconds duration (by measurement and ab initio calculation) reveals the feasibility of dielectric optical switching at clock rates above 100 terahertz. The observed sub-femtosecond rise of energy transfer from the field to the material (for a peak electric field strength exceeding 2.5 volts per ångström) in turn indicates the viability of petahertz-bandwidth metrology with a solid-state device.
RESUMEN
BACKGROUND: The difference in diagnostic yield between surgical lung biopsy and transbronchial lung cryobiopsy (TBLC) in diffuse parenchymal lung diseases (DPLD) has been reported to be due to differences in the rate of interpathologist agreement, specimen size, and specimen adequacy. In TBLC, the specimens containing large airway components are generally believed as inadequate specimens for histological evaluation, but the detailed characteristics of TBLC specimens including the large airway and the impact on histological diagnostic rates of DPLD have not been investigated. METHODS: We retrospectively reviewed the specimen characteristics of patients with DPLD who underwent TBLC. RESULTS: Between February 2018 and January 2020, 74 patients and 177 specimens were included. There were 85 (48.0%) large airway specimens (LAS) that contained bronchial gland or bronchial cartilage. The ideal specimen ratio was significantly lower in the LAS-positive group than that in the LAS-negative group (5.8% vs. 45.6%), and the proportion of bronchioles, alveoli, and perilobular area were similarly lower in the LAS-positive group. The presence of traction bronchiectasis and diaphragm overlap sign on high-resolution computed tomography (HRCT) were also significantly higher in the LAS-positive group than those in the LAS-negative group. We observed a statistically significant trend in histological diagnostic yield (40.7% in LAS positive group; 60.8% in LAS positive and negative group; 91.6% in LAS negative group) (Cochran-Armitage trend test). CONCLUSION: LAS is a specimen often collected in TBLC and contains a low percentage of bronchioles, alveoli, and perilobular area. Since the histological diagnostic yield tends to be higher in cases that do not contain LAS, it may be important to determine the biopsy site that reduces the frequency of LAS collection by referring to the HRCT findings in TBLC.
Asunto(s)
Broncoscopía , Enfermedades Pulmonares Intersticiales , Humanos , Broncoscopía/métodos , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/patología , Pulmón/diagnóstico por imagen , Pulmón/patología , Biopsia/métodosRESUMEN
BACKGROUND: Elevated circulating levels of YKL-40 correlate with disease severity in Cystic Fibrosis (CF), but the role of YKL-40 in the inflammatory response in CF is still under investigation. Our main goal was to evaluate if YKL-40 can modulate the expression of major cytokines (IL-6, IL-10, IL-13) implicated in the inflammatory response in CF. A secondary goal was to explore the interactions between YKL-40 and other circulating proteins to determine the impacts on cytokine modulation. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of 83 adult CF patients in stable clinical condition. PBMCs were treated with human YKL-40 followed by the measure of IL-6, IL-10 and IL-13 gene expression. Protein arrays were used to explore the interactions between YKL-40 and circulating proteins. Interaction with Galectin-3 (GAL3) was identified, and confirmed by binding assay. Cytokine gene expressions were again monitored by RT-qPCR after PBMC treatment with GAL3, with or without YKL-40 co-stimulation. RESULTS: Following YKL-40 stimulation, PBMC gene expression of IL-6, IL-10 and IL-13 varies across patients. IL-6 and IL-13 are coexpressed, but this response was different in male and female patients. GAL3 protein was detected in the blood of CF patients, and a molecular interaction with YKL-40 was identified. GAL3 did not interfere with the YKL-40 stimulation of IL-6, IL-10 and IL-13 but may modulate the coexpression. CONCLUSION: We observed that YKL-40 stimulation had a variable impact on IL-6, IL-10, and IL-13 gene expression in CF PBMCs and uncovered an interaction between GAL3 and YKL-40 in the serum of CF patients. Our findings suggest that YKL-40 is not only a biomarker of disease severity in CF, but it might play an active role in the inflammatory pathophysiology of the disease.
Asunto(s)
Proteína 1 Similar a Quitinasa-3/sangre , Fibrosis Quística/sangre , Galectina 3/sangre , Leucocitos Mononucleares/metabolismo , Adulto , Citocinas/metabolismo , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Unión ProteicaRESUMEN
BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) can occur without self-awareness of symptoms. We aimed to investigate characteristics of patients with a tissue-based diagnosis of TIA but having no self-awareness of their symptoms and whose symptoms were witnessed by bystanders. METHODS: We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self-awareness of their TIA symptoms. RESULTS: Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self-awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self-awareness. Patients without self-awareness of symptoms arrive at hospitals earlier than those with self-awareness (P < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.
Asunto(s)
Fibrilación Atrial , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Masculino , Sistema de Registros , Factores de Riesgo , Accidente Cerebrovascular/epidemiologíaRESUMEN
INTRODUCTION: Survival of childhood cancer has increased over the past decades. This has led to the development of strategies aiming to enhance follow-up care and research, for which priorities may vary globally. We explored perspectives of an international healthcare workers panel. METHODS: Attendants of a meet-the-expert session on childhood cancer survivorship at the 2018 SIOP conference completed a survey about their view on important follow-up care and research aspects for survivors below and over 18 years. We analysed overarching categories and subtopics, and compared Asian versus European and North American healthcare workers. RESULTS: A total of 58 participants from different medical specialties (67.2% paediatric oncologists) and continents (48.3% Asia, 39.7% Europe/North America) responded. Follow-up care priorities for survivors below and over 18 years included physical care (39.3% ≤18 years, 35.9% >18 years) and healthcare structure (29.4%, 26.0%). Physical care was also the most important research aspect for both age groups (52.5%, 50.7%). Psychological support was the most frequently reported subtopic. Asian clinicians (n = 22) primarily prioritized physical care aspects of follow-up care, whereas European/North American (n = 19) clinicians underscored the importance of healthcare structure. CONCLUSION: Physical care is the most important aspect of survivorship care and research according to clinicians from several continents. Asian and European/North American respondents shared most priorities, however, healthcare structure was a more important category for European/North American clinicians. The most common subtopic was psychological support, underlining also the need to involve psychologists in follow-up.
Asunto(s)
Supervivientes de Cáncer , Neoplasias , Cuidados Posteriores , Niño , Humanos , Neoplasias/terapia , Encuestas y Cuestionarios , SobrevivientesRESUMEN
BACKGROUND: Complete mesocolic excision with central vessel ligation may be important for accurate staging and improving the prognosis of right-sided colon cancer. Although the procedure is often performed laparoscopically, approaching the middle colic artery (MCA) is technically demanding, especially when complete ligation of arteries at their roots is desired. We standardized our laparoscopic approach by establishing the dissection boundary along the superior mesenteric artery to achieve D3 lymphadenectomy in the region of the MCA. The aim of the present study was to evaluate, on the basis of perioperative and short-term oncologic outcomes, the feasibility and safety of our technique METHODS: We conducted a retrospective study on consecutive patients with cancer located at the ascending colon and transverse colon who had laparoscopic right hemicolectomy requiring ligation of the MCA. RESULTS: There were 41 patients (22 males, median age 71 years [range 49-86] years). The median operation time was 285 min, and blood loss volume was 40 mL. Conversion to open surgery was required in 1 case. Complications that were Clavien-Dindo grade III or above occurred in 3 patients (7.3%). There was no anastomotic leakage. The median number of lymph nodes harvested was 46. CONCLUSIONS: Our technique was shown to be a safe, feasible, and useful strategy for performance of right hemicolectomy requiring ligation of the MCA in cases of colon cancer. The technique facilitates maximal lymph node dissection. Having obtained favorable outcomes, we look forward to investigation into long-term outcomes.
Asunto(s)
Neoplasias del Colon , Laparoscopía , Mesocolon , Anciano , Anciano de 80 o más Años , Colectomía , Neoplasias del Colon/cirugía , Humanos , Ligadura , Escisión del Ganglio Linfático , Masculino , Arteria Mesentérica Inferior/cirugía , Arteria Mesentérica Superior , Mesocolon/cirugía , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant proteins within the alveolar spaces. Autoimmune PAP (APAP) caused by elevated levels of GM-CSF autoantibodies (GM-Ab) is very rarely associated with systemic autoimmune disease. Here we report a case of APAP manifested during immunosuppressive treatment for polymyositis with interstitial lung disease. CASE PRESENTATION: A 52-year-old woman treated at our hospital because of polymyositis with interstitial pneumonia had maintained remission by immunosuppressive treatment for 15 years. She had progressive dyspnea subsequently over several months with her chest CT showing ground-glass opacities (GGO) in bilateral geographic distribution. Her bronchoalveolar lavage fluid with cloudy appearance revealed medium-sized foamy macrophages and PAS-positive amorphous eosinophilic materials by cytological examination. We diagnosed her as APAP due to an increased serum GM-CSF autoantibody level. Attenuating immunosuppression failed to lead GGO improvement, but whole lung lavage (WLL) was effective in her condition. CONCLUSIONS: PAP should be considered as one of the differential diseases when the newly interstitial shadow was observed during immunosuppressive treatment. WLL should be regarded as the treatment option for APAP concurred in connective tissue disease (CTD).
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Polimiositis/complicaciones , Proteinosis Alveolar Pulmonar/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Disnea/etiología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Humanos , Inmunosupresores/efectos adversos , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Persona de Mediana Edad , Polimiositis/tratamiento farmacológico , Proteinosis Alveolar Pulmonar/inmunología , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Tomografía Computarizada por Rayos XRESUMEN
Charge density waves (CDWs) are symmetry-broken ground states that commonly occur in low-dimensional metals due to strong electron-electron and/or electron-phonon coupling. The nonequilibrium carrier distribution established via photodoping with femtosecond laser pulses readily quenches these ground states and induces an ultrafast insulator-to-metal phase transition. To date, CDW melting has been mainly investigated in the single-photon regime with pump photon energies bigger than the gap size. The recent development of strong-field midinfrared sources now enables the investigation of CDW dynamics following subgap excitation. Here we excite prototypical one-dimensional indium wires with a CDW gap of â¼300 meV with midinfrared pulses at âω=190 meV with MV/cm field strength and probe the transient electronic structure with time- and angle-resolved photoemission spectroscopy. We find that the CDW gap is filled on a timescale short compared to our temporal resolution of 300 fs and that the band structure changes are completed within â¼1 ps. Supported by a minimal theoretical model we attribute our findings to multiphoton absorption across the CDW gap.
RESUMEN
BACKGROUND: Lupus nephritis (LN) is a major determinant of mortality in systemic lupus erythematosus (SLE). Here we evaluated the association between complete renal response (CR) and mortality in LN. METHODS: We retrospectively analyzed the cases of 172 of 201 patients with LN for whom data on the therapeutic response at 6 and 12 months after induction therapy were available. The patients underwent a renal biopsy at Nagasaki University Hospital and community hospitals in Nagasaki between the years 1990 and 2016. We determined the CR rates at 6 and 12 months after induction therapy initiation and evaluated the predictive factors for CR and their relationship with mortality. We performed univariate and multivariable competing risks regression analyses to determine the factors predictive of CR. The patients' survival data were analyzed by the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up duration after renal biopsy was 120 months (interquartile range: 60.3-191.8 months). The 5-, 10-, 15- and 20-year survival rates of our cohort were 99.3, 94.6, 92.0 and 85.4%, respectively. During follow-up, nine patients (5.2%) died from cardiovascular events, infection, malignancy and other causes. The multivariate analysis revealed that the following factors were predictive of CR. At 6 months: male gender (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.08-0.65, p = 0.0028), proteinuria (g/gCr) (OR 0.83, 95% CI 0.71-0.97, p = 0.0098) and index of activity (0-24) (OR 0.84, 95% CI 0.71-0.99, p = 0.0382). At 12 months: male gender (OR 0.25, 95% CI 0.09-0.67, p = 0.0043) and index of activity (0-24) (OR 0.82, 95% CI 0.69-0.98, p = 0.0236). The Kaplan-Meier analysis showed that compared to not achieving CR at 12 months, achieving CR at 12 months was significantly correlated with the survival rate (OR 0.18, 95% CI 0.04-0.92, p = 0.0339). CONCLUSIONS: Our results suggest that the survival rate of patients with LN is associated with the achievement of CR at 12 months after induction therapy, and that male gender and a higher index of activity (0-24) are the common predictive factors for failure to achieve CR at 6 and 12 months.
Asunto(s)
Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/mortalidad , Prednisolona/uso terapéutico , Adulto , Edad de Inicio , Estudios de Casos y Controles , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Proteinuria , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
BACKGROUND: Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE). METHODS: We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993-2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares. RESULTS: Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5-154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44-0.90, p = 0.00048) and serum ß2 microglobulin (MG) (OR 0.26, 95% CI 0.06-0.74, p = 0.00098) levels. CONCLUSIONS: Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum ß2MG levels were negative predictive factors of CR at 12 months.
Asunto(s)
Hospitales Universitarios , Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/etiología , Adulto , Autoantígenos/sangre , Nitrógeno de la Urea Sanguínea , Femenino , Estudios de Seguimiento , Humanos , Japón , Estimación de Kaplan-Meier , Riñón/patología , Modelos Logísticos , Nefritis Lúpica/sangre , Nefritis Lúpica/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fragmentos de Péptidos/sangre , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Microglobulina beta-2/sangreRESUMEN
BACKGROUND: Trappin-2/pre-elafin is an endogenous inhibitor of human neutrophil elastase involved in inflammation, innate immunity and vascular remodelling, which consist of the complex pathological process of systemic sclerosis (SSc). OBJECTIVES: To clarify the potential role of trappin-2 in SSc. METHODS: Serum trappin-2 levels were determined by enzyme-linked immunosorbent assay in 51 SSc and 18 healthy subjects. Trappin-2 expression was evaluated in SSc lesional skin and cultured endothelial cells treated with FLI1 siRNA by immunohistochemistry, reverse transcription-real-time PCR and/or immunoblotting. Friend leukaemia virus integration 1 (Fli1) binding to the PI3 promoter was assessed by chromatin immunoprecipitation. RESULTS: Since serum trappin-2 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction, SSc patients with normal renal function were analysed. Although serum trappin-2 levels were comparable between diffuse cutaneous SSc, limited cutaneous SSc and control subjects, the prevalence of digital ulcers or elevated right ventricular systolic pressure (RVSP) was significantly higher in SSc patients with elevated serum trappin-2 levels than in those with normal levels. Furthermore, serum trappin-2 levels were significantly increased in SSc patients with digital ulcers or elevated RVSP compared to those without. Moreover, serum trappin-2 levels positively correlated with RVSP values in SSc patients. Importantly, trappin-2 expression was enhanced in small vessels of SSc lesional skin. In cultured endothelial cells, trappin-2 expression was elevated by gene silencing of FLI1 at mRNA and protein levels and Fli1 occupied the PI3 promoter. CONCLUSIONS: Endothelial trappin-2 up-regulation partially due to Fli1 deficiency can be associated with the development of SSc vasculopathy.
Asunto(s)
Elafina/sangre , Esclerodermia Sistémica/sangre , Úlcera Cutánea/etiología , Disfunción Ventricular Derecha/etiología , Anciano , Presión Sanguínea , Vasos Sanguíneos/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Células Endoteliales , Femenino , Silenciador del Gen , Humanos , Masculino , Persona de Mediana Edad , Proteína Proto-Oncogénica c-fli-1/genética , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/genética , Piel/irrigación sanguínea , Úlcera Cutánea/sangre , Sístole , Regulación hacia Arriba , Disfunción Ventricular Derecha/sangreRESUMEN
BACKGROUND: Increased level of hydrogen sulphide (H2 S) in sputum is reported to be a new biomarker of neutrophilic airway inflammation in chronic airway disorders. However, the relationship between H2 S and disease activity remains unclear. OBJECTIVE: We investigated whether H2 S levels could vary during different conditions in asthma. METHOD: H2 S levels in sputum and serum were measured using a sulphide-sensitive electrode in 47 stable asthmatic subjects (S-BA), 21 uncontrolled asthmatic subjects (UC-BA), 26 asthmatic subjects with acute exacerbation (AE-BA) and 15 healthy subjects. Of these, H2 S levels during stable, as well as exacerbation states, were obtained in 13 asthmatic subjects. RESULTS: Sputum H2 S levels were significantly higher in the AE-BA subjects compared to the UC-BA and healthy subjects (P < .05). However, serum H2 S levels in the AE-BA subjects were lower than in the S-BA subjects (P < .001) and similar to those in healthy subjects. Thus, the sputum-to-serum ratio of H2 S (H2 S ratio) in the AE-BA subjects was significantly higher than in the S-BA, UC-BA and healthy subjects (P < .05). Among all subjects, sputum H2 S levels showed a trend to decrease with FEV1 %predicted and significantly positive correlations with sputum neutrophils (%), sputum IL-8 and serum IL-8. A multiple linear regression analysis showed that sputum H2 S was independently associated with increased sputum neutrophils (%) and decreased FEV1 %predicted (P < .05). The cut-off level of H2 S ratio to indicate an exacerbation was ≥0.34 (area under the curve; 0.88, with a sensitivity of 81.8% and specificity of 72.7%, P < .001). Furthermore, half of the asthmatic subjects with H2 S ratios higher than the cut-off level experienced asthma exacerbations over the following 3 months after enrolment. CONCLUSIONS: The H2 S ratio may provide useful information on predicting future risks of asthma exacerbation, as well as on obstructive neutrophilic airway inflammation as one of the non-Th2 biomarkers, in asthma.
Asunto(s)
Asma/inmunología , Asma/metabolismo , Biomarcadores , Sulfuro de Hidrógeno/metabolismo , Esputo/metabolismo , Adulto , Anciano , Asma/diagnóstico , Estudios Transversales , Citocinas/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Sulfuro de Hidrógeno/sangre , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Neutrófilos/metabolismo , Pronóstico , Curva ROC , Pruebas de Función Respiratoria , Células TH1/inmunología , Células TH1/metabolismo , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}â1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}â1/2^{+}), E1(1/2^{-}â1/2^{+}), and E1(1/2^{-}â3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.
RESUMEN
BACKGROUND: Interleukin (IL)-25 is a member of the IL-17 family, which can promote and augment T-helper (Th) type 2 responses. The expression of IL-25 and its cognate receptor, IL-25 receptor (IL-25R), is upregulated and correlated with disease activity in Th2-associated diseases. OBJECTIVES: To examine the expression and function of IL-25 in cutaneous T-cell lymphoma (CTCL). METHODS: Expression and location of IL-25 in lesional skin was investigated with immunohistochemistry. The effect of various cytokines on IL-25 production from normal human epidermal keratinocytes was assessed by quantitative reverse-transcription real-time polymerase chain reaction. Serum IL-25 levels were measured by enzyme-linked immunosorbent assay. The direct effect of IL-25 on tumour cells was also examined using CTCL cell lines and peripheral blood mononuclear cells in patients with Sézary syndrome. RESULTS: IL-25 expression was increased in epidermal keratinocytes in lesional skin of CTCL. Th2 cytokines, IL-4 and IL-13, and periostin induced IL-25 expression by normal human epidermal keratinocytes. Serum IL-25 levels were increased in patients with advanced CTCL and correlated with serum lactate dehydrogenase levels. MyLa cells expressed IL-25R and its expression was augmented by stimulation with IL-25. IL-25 enhanced IL-13 production from MyLa cells via phosphorylation of signal transducer and activator of transcription 6. Peripheral blood mononuclear cells from one patient with Sézary syndrome expressed IL-25R and showed increase of IL-13 production by IL-25. CONCLUSIONS: Th2 cytokines highly expressed in CTCL lesional skin induce IL-25 production by epidermal keratinocytes, which may, in turn, lead to formation of a Th2-dominant microenvironment through the direct induction of IL-13 by tumour cells.
Asunto(s)
Interleucina-17/fisiología , Linfoma Cutáneo de Células T/inmunología , Células Th2/inmunología , Microambiente Tumoral/inmunología , Línea Celular , Progresión de la Enfermedad , Femenino , Humanos , Interleucina-13/biosíntesis , Interleucina-17/metabolismo , Queratinocitos/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Fosforilación/inmunología , Receptores de Interleucina/inmunología , Factor de Transcripción STAT6/metabolismo , Regulación hacia Arriba/inmunologíaRESUMEN
Systemic lupus erythematosus (SLE) involves multiple organ systems and primarily affects women during their reproductive years. Pregnancy in a woman with SLE may lead to higher rates of disease flares. Little is known regarding which medications are safe to maintain remission and/or treat flares throughout such pregnancies. Here we retrospectively analyzed the efficacy of tacrolimus (TAC) in the pregnancy outcomes of SLE patients. We studied the 54 deliveries of 40 SLE patients over an eight-year period from 2008 to 2016. We used analyses of covariance with adjustments for the propensity score and inverse probability of treatment weights to compare the patient backgrounds between the TAC users and non-TAC users. TAC was administered to the patient in 15 of the 54 (27.8%) pregnancies, and these patients had a significantly higher dose of prednisolone, hypocomplementemia, lower estimated glomerular filtration rate, past history of lupus nephritis, and complication with antiphospholipid syndrome. In the adjusted background of the TAC deliveries, the risks of decreased fetal body weight, low birth weight infant, non-reassuring fetal status (NRFS), and preterm birth were not increased compared to the non-TAC deliveries. Thrombocytopenia and hypertension during the pregnancy were extracted as independent predictive risk factors for decreased fetal body weight and NRFS, respectively. We had anticipated that the maternal and fetal outcomes in the TAC-use deliveries would be poor before the analysis; however, the TAC-use group showed no significant difference in risks contributing to outcomes compared to the non-TAC group, suggesting that adjunct TAC treatment corrected various risk factors during the lupus pregnancies.