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1.
J Colloid Interface Sci ; 630(Pt B): 704-713, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36347097

RESUMO

The degradation and mineralization of volatile organic compounds (VOCs) in gas-solid phase photocatalytic systems suffer great challenges due to the low electron transfer efficiency and slow benzene ring-opening kinetics. Hence, a heterojunction photocatalyst of Bi2SiO5/TiO2 has been synthesized by a facile method. Bi2SiO5/TiO2 shows the ability of mineralizing toluene to CO2 with a degradation rate of 85.5%, while TiO2 is 49.0% and presents a continuous deactivation. Experimental characterizations and theoretical calculations indicate that a unique electron transfer channel of Bi/Si-O-Ti can be established in the heterojunction sample due to the coupling of the interface. The channel facilitates electron transfer to the catalyst surface, generating •OH radicals with strong oxidation and ring-opening ability. Moreover, in-situ DRIFTS reveal that the selective generation of benzoic acid on Bi2SiO5/TiO2 heterojunction plays a critical role in the ring-opening of toluene. This work discloses a novel paradigm to obtain the deep and durable photocatalytic mineralization of toluene.


Assuntos
Radical Hidroxila , Tolueno , Elétrons , Titânio
3.
Front Pharmacol ; 13: 975250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386180

RESUMO

Long noncoding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides that have little or no coding potential. LncRNAs function as key regulators in diverse physiological and pathological processes. However, the roles of lncRNAs in lipopolysaccharide (LPS)-induced acute liver injury (ALI) are still elusive. In this study, we report the roles of lncRNA Gm26917 induced by LPS in modulating liver inflammation. As key components of the innate immune system, macrophages play critical roles in the initiation, progression and resolution of ALI. Our studies demonstrated that Gm26917 localized in the cytoplasm of hepatic macrophages and globally regulated the expression of inflammatory genes and the differentiation of macrophages. In vivo study showed that lentivirus-mediated gene silencing of Gm26917 attenuated liver inflammation and protected mice from LPS-induced ALI. Furthermore, mechanistic study showed that the 3'-truncation of Gm26917 interacted with the N-terminus of Annexin A1, a negative regulator of the NF-κB signaling pathway. We also found that Gm26917 knockdown suppressed NF-κB activity by decreasing the ubiquitination of Annexin A1 and its interaction with NEMO. In addition, expression of Gm26917 in inflammatory macrophages was regulated by the transcription factor forkhead box M1 (FOXM1). LPS treatment dramatically increased the binding of FOXM1 to the promoter region of Gm26917 in macrophages. In summary, our findings suggest that lncRNA Gm26917 silencing protects against LPS-induced liver injury by regulating the TLR4/NF-κB signaling pathway in macrophages.

4.
Front Cardiovasc Med ; 9: 949558, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386341

RESUMO

Purpose: The aim of this study was to describe the treatment technique, outcomes, and complications of Schobinger stage IV head and neck arteriovenous malformations (HNAVMs) with associated high-output cardiac failure (HOCF) using ethanol and coils with the percutaneous suture technique. Methods: From January 2015 to December 2019, 19 patients who had HNAVMs with associated HOCF were treated first with a percutaneous suture of the remarkably dilated dominant drainage vein (RDDOV) and subsequent embolization with coils and ethanol. The percutaneous suture of RDDOV was preferred to be performed, followed by the deployment of coils and the injection of absolute ethanol via transarterial approach, direct puncture approach, or both of them. Treatment outcomes and complication rates were evaluated at follow-up. Results: A total of 19 patients who experienced HNAVMs with HOCF received 19 percutaneous suture procedures and 84 embolization procedures with ethanol and coils. Complete or >90% shunt reduction of the AVM was achieved in 16 patients. Notably, 19 patients with New York Heart Association (NYHA) stage II improved to stage I, and the symptom of dyspnea disappeared after embolization. The symptoms of five patients with bleeding disappeared. All patients presented with cosmetic concerns; Four were cured, and eight had a clearly recognizable improvement. Of note, 19 (100%) patients presented with impairment of daily life, which was resolved. The minor complications were encountered and recovered by the self. No major complications occurred. Conclusion: This study provides evidence that ethanol and coil embolotherapy is effective and safe in treating HOCF caused by HNAVMs with acceptable complications in these cases. The percutaneous suture technique for RDDOV management can act as an adjunct for embolotherapy.

5.
Therap Adv Gastroenterol ; 15: 17562848221131132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406056

RESUMO

Background: Postprocedural delayed bleeding (PDB) remains the most common major complication of colorectal polypectomy. Incomplete clip closure of mucosal defect and unclosed injured blood vessels in gaps between clips may be the risk factors for PDB. Objectives: To observe whether completely no-gap closure of mucosal defect after polypectomy can reduce PDB occurrence. Design: Single-center, retrospective case-control study. Methods: In this study based on historical comparisons of patients in 2 time periods, only the patients with polyps sized between 6 and 15 mm were included. A new clip-assisted endoloop ligation (CAEL, treatment group) method was used between January 2019 and December 2020, and a traditional simple clip closure (SCC, control) was used Between January 2017 and December 2018 to prevent PDB after polypectomy. The rate of PDB of two groups and risk factors for PDB were evaluated. Results: Totally 4560 patients were included in the study; 2418 patients belong to CAEL group, and 2142 patients belong to SCC group. The overall rate of PDB was significantly lower in CAEL group compared to SCC group (0.6% versus 1.5%, p < 0.00). On multivariate logistic analysis, CAEL was a significant independent preventive factor for PDB (odds ratio (OR), 0.092; 95% confidence interval (CI), 0.029-0.3335; p = 0.000). Polyps located at rectum (colon versus rectum) represented a significant independent risk factor for PDB (OR, 11.888; 95% CI, 3.343-42.269; p = 0.001). Conclusion: Completely no-gap closure of mucosal defect after polypectomy further reduced the rate of PDB for polyps sized between 6 and 15 mm. CAEL may be a significant independent preventive factor for PDB. Polyps located at the rectum may be a significant independent risk factor for PDB.

6.
Front Immunol ; 13: 1015831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405702

RESUMO

Inducible costimulator (ICOS) and its ligand (ICOSL) are critical to regulate the immune response in autoimmune diseases. The participation of B lymphocytes exhibits pathogenic potential in the disease process of rheumatoid arthritis (RA). However, the precise role of ICOSL in RA remains unclear. In this study, we aimed to explore the regulatory effects of CD19+ICOSL+ B cells in the pathogenesis of RA. We demonstrated the increased expression of ICOS and ICOSL in patients with RA and collagen-induced arthritis (CIA) mice. The population of CD19+ICOSL+ B-cell subset was significantly correlated with clinicopathological characteristics of RA patients and CIA mice. Adoptive transfer of CD19+ICOSL+ B cells aggravated arthritic progression in CIA mice. Moreover, microarray analysis revealed that CD19+ICOSL+ cells could exert pivotal effect in pathological process of RA. Further blocking of ICOSL significantly inhibited proinflammatory responses and ameliorated arthritic progression. Therefore, CD19+ICOSL+ B-cell subset could be defined as a specific pathogenic cell subpopulation involved in immunopathological damage of RA. Blockade of ICOSL is promising to be a potential new approach for RA therapy.


Assuntos
Artrite Experimental , Artrite Reumatoide , Camundongos , Animais , Ligantes , Ligante Coestimulador de Linfócitos T Induzíveis , Linfócitos B , Antígenos CD19 , Proteínas Adaptadoras de Transdução de Sinal
7.
Anal Chim Acta ; 1235: 340553, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368829

RESUMO

A paper-based chemiresistive sensor consisting of a single-walled carbon nanotubes network with electrodeposited gold nanoparticles (AuNPs-SWCNTs) was developed for the sensitive detection of As(III). A new sensing strategy was also proposed combined with a paper-based device for As(III) chemiresistive detection based on the electrochemical doping of As(0) on the AuNPs-SWCNTs channel. The proposed paper-based chemiresistive sensor was manufactured by wax printing and vacuum deposition using a water-based SWCNTs ink. The sensor sensitivity was enhanced by optimizing the volume of SWCNTs ink used in the formation of the sensing network in the paper and the sweep segment of cyclic voltammetry used for the electrochemical deposition of AuNPs. Additionally, the mechanism of the sensing strategy based on the electrochemical n-doping of As(0) to the AuNPs-SWCNTs sensing channel was investigated using a liquid-ion gated FET system. The As(III) concentration detected by the as-fabricated chemiresistive sensor is as low as 1.35 × 10-5 µM which is even lower than the maximum permissible concentration in drinking water defined by the WHO. In this paper, we provide a simple strategy for developing paper-based chemiresistive sensors with unique properties for practical As(III) determination.


Assuntos
Nanopartículas Metálicas , Nanotubos de Carbono , Ouro/química , Nanotubos de Carbono/química , Técnicas Eletroquímicas , Nanopartículas Metálicas/química , Eletrodos
8.
Artigo em Inglês | MEDLINE | ID: mdl-36374898

RESUMO

Traditional convolutional neural networks (CNNs) share their kernels among all positions of the input, which may constrain the representation ability in feature extraction. Dynamic convolution proposes to generate different kernels for different inputs to improve the model capacity. However, the total parameters of the dynamic network can be significantly huge. In this article, we propose a lightweight dynamic convolution method to strengthen traditional CNNs with an affordable increase of total parameters and multiply-adds. Instead of generating the whole kernels directly or combining several static kernels, we choose to "look inside", learning the attention within convolutional kernels. An extra network is used to adjust the weights of kernels for every feature aggregation operation. By combining local and global contexts, the proposed approach can capture the variance among different samples, the variance in different positions of the feature maps, and the variance in different positions inside sliding windows. With a minor increase in the number of model parameters, remarkable improvements in image classification on CIFAR and ImageNet with multiple backbones have been obtained. Experiments on object detection also verify the effectiveness of the proposed method.

9.
BMC Infect Dis ; 22(1): 828, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352359

RESUMO

BACKGROUND: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period. METHODS: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The distribution of the incubation period was estimated using the generalized odds-rate class of regression models. RESULTS: From 406 surveyed patients, 242 provided adequate information to be included in the analysis. The median incubation period was 2.8 days (95%CI: 2.5-3.1) and no differences between vaccinated and unvaccinated patients were found. Sex and age are neither shown not to be significantly related to the COVID-19 incubation time. CONCLUSIONS: Knowing the incubation period is crucial for controlling the spread of an infectious disease: decisions on the duration of the quarantine or on the periods of active monitoring of people who have been at high risk of exposure depend on the length of the incubation period. Furthermore, its probability distribution is a key element for predicting the prevalence and the incidence of the disease.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/prevenção & controle , Espanha/epidemiologia , Estudos de Coortes , Período de Incubação de Doenças Infecciosas , Vacinação
10.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364921

RESUMO

Placental extract has been used for skin care and delaying skin aging. Cow placenta is an abundant resource with a large mass, which has not been harnessed effectively. Cow placenta extract (CPE) has the functions of antioxidation, anti-inflammatory, promoting growth and development, and promoting hair growth. However, little is known about the effect of oral administration of cow placenta extract on skin conditions. Therefore, the present study aimed to investigate the antioxidant capacity of CPE in vitro and in vivo and its protective effect on d-galactose (D-gal) induced skin aging in mice. The results showed that CPE had strong free radical scavenging, reducing and metal chelating activities. CPE can increase the activity of catalase (CAT), glutathione peroxidase (GSH-Px), peroxidase (POD), superoxide dismutase (SOD), and the content of glutathione (GSH), decrease the content of malondialdehyde (MDA). Moreover, CPE can decrease the gene and protein expression of matrix metalloproteinase 1a (MMP-1a) and matrix metalloproteinase 3 (MMP-3) and increase the expression of transforming growth factor-ß (TGF-ß) and tissue inhibitor of metalloproteinase 1 (TIMP-1) of mouse skin. Histopathological analysis showed CPE reduced the collagen damage caused by D-gal, increased collagen synthesis and reduced its degradation to delay skin aging.


Assuntos
Antioxidantes , Envelhecimento da Pele , Animais , Bovinos , Feminino , Camundongos , Gravidez , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Galactose/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Extratos Vegetais/farmacologia , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo
11.
J Agric Food Chem ; 70(45): 14377-14385, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36331134

RESUMO

Little is known about the effect of nano sulfur (NS) under field conditions as a multifunctional agricultural amendment. Pristine and surface coated NS (CS) were amended in soil at 200 mg/kg that was planted with tomato (Solanum lycopersicum) and infested with Fusarium oxysporum f. sp. lycopersici. Foliar exposure of CS (200 µg/mL) was also included. In healthy plants, CS increased tomato marketable yield up to 3.3∼3.4-fold compared to controls. In infested treatments, CS significantly reduced disease severity compared to the other treatments. Foliar and soil treatment with CS increased yield by 107 and 192% over diseased controls, respectively, and significantly increased fruit Ca, Cu, Fe, and Mg contents. A $33/acre investment in CS led to an increase in marketable yield from 4920 to 11,980 kg/acre for healthy plants and from 1135 to 2180 kg/acre for infested plants, demonstrating the significant potential of this nanoenabled strategy to increase food production.


Assuntos
Fusarium , Lycopersicon esculentum , Nanopartículas , Biofortificação , Doenças das Plantas/prevenção & controle , Solo , Nutrientes
12.
Neuropsychiatr Dis Treat ; 18: 2713-2723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419859

RESUMO

Objective: The timing of tracheostomy (TR) in severe stroke patients receiving mechanical ventilation has not been determined. In this study, we compared some prognostic indicators of early tracheostomy (ET) and late tracheostomy (LT). A meta-analysis was performed to obtain a higher level of evidence of the timing of TR in patients with severe stroke receiving mechanical ventilation. Methods: The study was a retrospective single-center study. We divided the severe stroke patients who received TR from June 2020 to June 2022 into the ET group and LT group. The demographic characteristics, clinical characteristics and prognostic indices were compared. For this meta-analysis, we systematically searched PubMed and other databases. The compared prognostic indicators included mechanical ventilation time, ICU length of stay (LOS), total LOS, ventilator-related pneumonia (VAP) incidence, and mortality. Results: A total of 61 patients were included in our study, including 32 patients in the ET group and 29 patients in the LT group. Univariate and multivariate analyses showed that the NIHSS score in the ET group was higher than that in the LT group (P < 0.05). In terms of outcome indicators, compared with the LT group, the median mechanical ventilation time in the ET group was shortened by 5.5 days (P = 0.034). The ICU LOS and total LOS in the ET group were significantly lower than those in the LT group (median 14.5 days vs 22 days, P = 0.004; 21 days vs 27 days, P = 0.019). The meta-analysis showed that ET could significantly shorten the ICU LOS (MD -3.89 [95% CI: -6.86, -0.92]) and the total LOS (MD -7.70 [95% CI: -8.57, -6.83]) and significantly reduce the occurrence of VAP (OR 0.75 [95% CI: 0.64, 0.87]). Conclusion: The results of our retrospective study and meta-analysis support that ET can shorten the ICU LOS and total LOS and reduce the occurrence of VAP. Therefore, it has a positive effect on the prognosis of patients with severe stroke who need mechanical ventilation support.

13.
J Natl Cancer Inst ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36346180

RESUMO

BACKGROUND: There is a lack of evidence from nationwide sample on the disparity of initiating immune checkpoint inhibitors (ICIs) after metastatic lung cancer diagnosis. METHODS: We identified metastatic lung cancer patients diagnosed between 2015 and 2020 from a large nationwide commercial claims database. We analyzed the time from metastatic lung cancer diagnosis to ICI therapy using Cox proportional hazard models. Independent variables included county-level measures (quintiles of percentage of racialized population, quintiles of percentage of population below poverty, urbanity, and density of medical oncologists) and patient characteristics (age, sex, Charlson comorbidity index, Medicare Advantage, and year of diagnosis). All tests were two-sided. RESULTS: A total of 17,022 patients were included. Counties with a larger proportion of racialized population appeared to be more urban, have a greater percentage of its residents in poverty, and have a higher density of medical oncologists. In Cox analysis, the adjusted hazard ratio of the second, third, fourth, and highest quintile of percentage of racialized population were 0.89 (95% confidence interval [CI]: 0.82-0.98), 0.85 (95% CI: 0.78-0.93), 0.78 (95% CI: 0.71-0.86), and 0.71 (95% CI: 0.62-0.81), respectively, compared to counties in the lowest quintile. The slower ICI therapy initiation was driven by counties with the highest percentage of Hispanic population and other non-Black racialized groups. CONCLUSIONS: Commercially insured patients with metastatic lung cancer who lived in counties with greater percentage of racialized population had slower initiation of ICI therapy after lung cancer diagnosis, despite greater density of oncologists in their neighborhood.

14.
Sci Rep ; 12(1): 18829, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335251

RESUMO

Intramuscular injection of anemoside B4 (AB4) has a superior therapeutic effect on clinical mastitis in lactating cows. Here, we explored AB4's effect on milk whey in clinical mastitis-affected cows using proteomics. Among fifty clinical mastitis cows received AB4 administration (0.05 ml/kg/day, for 7 days), twelve healed cows were selected and marked as group T. Twelve clinically heathy cows received the same dose of saline for 7 days, marked as group C. Collected milk whey of group T before and after AB4 administration marked as T1 and T2, respectively. The milk whey of group C after saline injection marked as C1. Milk whey protein changes were detected using tandem mass tag-based quantitative proteomic. We identified 872 quantifiable proteins in the samples. Among them, 511 proteins between T1 and C1, and 361 proteins between T2 and T1 were significantly altered. T1 than C1 had significantly more proteins associated with inflammatory damage and trans-endothelial migration of leukocytes, whereas these proteins were reduced in T2 treated with AB4. Compared with C, proteins associated with fibrin clot degradation and complement system activation were downregulated in T1 but upregulated in T2. In summary, AB4 can exert its therapeutic effect on clinical mastitis in cows mainly by reducing inflammatory damage, activating the complement system, inhibiting trans-endothelial migration of leukocytes, and promoting degradation of milk fibrin clots.


Assuntos
Mastite Bovina , Leite , Animais , Bovinos , Feminino , Fibrina/metabolismo , Lactação , Mastite Bovina/tratamento farmacológico , Mastite Bovina/metabolismo , Leite/metabolismo , Proteínas do Leite/metabolismo , Proteômica , Soro do Leite/metabolismo , Proteínas do Soro do Leite/farmacologia , Proteínas do Soro do Leite/metabolismo
15.
Pathol Oncol Res ; 28: 1610699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330052

RESUMO

Purpose: This study aimed to investigate the applicability of plasma extracellular vesicles (EVs) miR-99a-5p as a potential head and neck squamous cell carcinoma (HNSCC) diagnostic biomarker. Methods: The miRNA expression of HNSCC tissue and plasma EVs were profiled by small RNA sequencing. qRT-PCR was performed to detect miR-99a-5p expression in HNSCC (n = 93) and benign disease (n = 39) plasma EVs and formalin-fixed and paraffin-embedded (FFPE) tissue (n = 110). We constructed receiver-operating characteristic curves to investigate the diagnostic efficiency of plasma EVs miR-99a-5p. Results: Tumor tissue exhibited lower miR-99a-5p than para-tumor tissue. Patients with high miR-99a-5p expression exhibited significantly more p16 positive status. In contrast, HNSCC plasma EVs harbored more miR-99a-5p than the benign disease group. Plasma EVs miR-99a-5p distinguished HNSCC with area under the curve (AUC) of 0.7494 (95% CI: 0.6692-0.8296; p < 0.0001), with 61.54% sensitivity and 75.27% specificity, respectively. Furthermore, plasma EVs miR-99a-5p also distinguished early HNSCC with AUC of 0.7394 (95% CI: 0.6284-0.8504; p = 0.0002), with 79.07% sensitivity and 61.54% specificity, respectively. Conclusion: Plasma EVs miR-99a-5p is a potential biomarker for predicting early HNSCC.


Assuntos
Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , MicroRNAs , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias de Cabeça e Pescoço/genética
16.
Commun Stat Theory Methods ; 51(22): 7830-7845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353187

RESUMO

Semi-competing risks data often arise in medical studies where the terminal event (e.g., death) censors the non-terminal event (e.g., cancer recurrence), but the non-terminal event does not prevent the subsequent occurrence of the terminal event. This article considers regression modeling of semi-competing risks data to assess the covariate effects on the respective non-terminal and terminal event times. We propose a copula-based framework for semi-competing risks regression with time-varying coefficients, where the dependence between the non-terminal and terminal event times is characterized by a copula and the time-varying covariate effects are imposed on two marginal regression models. We develop a two-stage inferential procedure for estimating the association parameter in the copula model and time-varying regression parameters. We evaluate the finite sample performance of the proposed method through simulation studies and illustrate the method through an application to Surveillance, Epidemiology, and End Results-Medicare data for elderly women diagnosed with early-stage breast cancer and initially treated with breast-conserving surgery.

17.
Virus Res ; 323: 198965, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36272540

RESUMO

Micropterus salmoides rhabdovirus (MSRV) has a high mortality rate and causes huge economic losses to the aquaculture industry. In this study, we identified that ursolic acid (UA) had antiviral efficacy against MSRV in vitro and in vivo. The results showed that UA inhibited MSRV replication in grass carp ovary (GCO) cells with a half-maximal inhibitory concentration (IC50) of 5.55 µM, reduced viral titers and decreased cytopathic effects (CPE). Mechanistically, UA does not directly damage viral particles. On the other hand, UA inhibits MSRV replication by altering viral binding and release. Furthermore, pre- and post-treatment assays revealed that UA had preventive and therapeutic effects. For in vivo studies, UA could enhance the survival rate of MSRV-infected largemouth bass. Similarly, UA reduced the viral load of MSRV in the heart, spleen and brain at 3, 5 and 7 d post-infection. In conclusion, UA is an effective inhibitor of rhabdovirus in aquaculture.

18.
Ann Hematol ; 101(12): 2627-2631, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36194257

RESUMO

Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Doenças de von Willebrand , Masculino , Humanos , Adulto , Doenças de von Willebrand/complicações , Doenças de von Willebrand/tratamento farmacológico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Fator de von Willebrand/metabolismo , Lenalidomida/uso terapêutico , Paraproteinemias/complicações , Paraproteinemias/tratamento farmacológico , Paraproteinemias/diagnóstico
19.
Lancet Oncol ; 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36306810

RESUMO

BACKGROUND: Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery, in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had an image-guided VACB-determined pathological complete response. METHODS: This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1-2N0-1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579. FINDINGS: Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled patients was 62 years (IQR 55-77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2-75·4). At a median follow-up of 26·4 months (IQR 15·2-39·6), no ipsilateral breast tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred. INTERPRETATION: Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed. FUNDING: US National Cancer Institute (National Institutes of Health).

20.
Front Immunol ; 13: 992819, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275719

RESUMO

Background: Interferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection. Methods: This retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan's National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, which was adjusted for potential confounders. Results: The median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR [aHR]: 0.96, 95% confidence interval [CI]: 0.81-1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71-1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence rate ratio: 1.33, 95% CI: 1.02-1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves' disease (aHR: 6.06, 95% CI: 1.27-28.8) and Hashimoto's thyroiditis (aHR 1.49, 95% CI 1.01-2.21) among IBT users. Conclusions: IBT use increases the risk of autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease) in patients with HCV infection to a greater extent than non-IBT use.


Assuntos
Doença de Graves , Doença de Hashimoto , Hepatite C Crônica , Hepatite C , Humanos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Ribavirina , Interferon-alfa , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco , Hepatite C/complicações , Doença de Hashimoto/complicações
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