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1.
Front Genet ; 15: 1376123, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233736

RESUMO

Inflammatory Bowel Disease (IBD) is believed to be a risk factor for Small Intestinal Neuroendocrine Tumors (SI-NET) development; however, the molecular relationship between IBD and SI-NET has yet to be elucidated. In this study, we use a systems biology approach to uncover such relationships. We identified a more similar transcriptomic-wide expression pattern between Crohn's Disease (CD) and SI-NET whereas a higher proportion of overlapping dysregulated genes between Ulcerative Colitis (UC) and SI-NET. Enrichment analysis indicates that extracellular matrix remodeling, particularly in epithelial-mesenchymal transition and intestinal fibrosis mediated by TIMP1, is the most significantly dysregulated pathway among upregulated genes shared between both IBD subtypes and SI-NET. However, this remodeling occurs through distinct regulatory molecular mechanisms unique to each IBD subtype. Specifically, myofibroblast activation in CD and SI-NET is mediated through IL-6 and ciliary-dependent signaling pathways. Contrarily, in UC and SI-NET, this phenomenon is mainly regulated through immune cells like macrophages and the NCAM signaling pathway, a potential gut-brain axis in the context of these two diseases. In both IBD and SI-NET, intestinal fibrosis resulted in significant metabolic reprogramming of fatty acid and glucose to an inflammatory- and cancer-inducing state. This altered metabolic state, revealed through enrichment analysis of downregulated genes, showed dysfunctions in oxidative phosphorylation, gluconeogenesis, and glycogenesis, indicating a shift towards glycolysis. Also known as the Warburg effect, this glycolytic switch, in return, exacerbates fibrosis. Corresponding to enrichment analysis results, network construction and subsequent topological analysis pinpointed 7 protein complexes, 17 hub genes, 11 microRNA, and 1 transcription factor related to extracellular matrix accumulation and metabolic reprogramming that are candidate biomarkers in both IBD and SI-NET. Together, these biological pathways and candidate biomarkers may serve as potential therapeutic targets for these diseases.

2.
J Pharm Bioallied Sci ; 16(Suppl 3): S2706-S2708, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39346341

RESUMO

Introduction: The permanent pacemaker implantation has a history of more than 60 years with improved mortality and quality of life but also recorded many complications. Objectives: The objective is to evaluate the rate of early complications at the National Heart Institute of Vietnam and the factors associated with the early complication of the permanent pacemaker implantation procedure. Methods: A cross-sectional descriptive is about 294 patients who received permanent pacemaker implantation at the National Heart Institute of Vietnam from 01/08/2020 to 30/30/2020. Results: The rate of complications is statistically higher in the diabetic group (OR = 2.5; 95% CI: 1.1-5.6), chronic kidney failure (OR = 2.7; 95% CI: 1.1-6.6), preheart surgery (OR = 3.8; 95% CI: 1.3-11.8), taking oral anticoagulants (OR = 4.3; 95% CI: 1.9-9.9), dual antiplatelets (OR = 2.95; 95% CI: 1.1-8.1), continuation to maintain anticoagulants, or dual antiplatelets (OR = 2.7; 95% CI: 1.2-6.4). Conclusion: Early onset of complications (onset of early complications) has been associated with some factors such as diabetes disease, chronic kidney failure, preheart surgery, oral anticoagulants, dual antiplatelets, continuation to maintain anticoagulation, and antiplatelets with statistical significance.

4.
Front Med (Lausanne) ; 11: 1396680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104857

RESUMO

Background: This study aimed to measure the associations between different inflammatory factors, namely interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hs-CRP), and atherosclerosis in patients with psoriasis vulgaris. Methods: A cross-sectional study was conducted at two hospitals in Hanoi, Vietnam. A total of 125 patients with psoriasis vulgaris and 50 healthy controls were recruited. Clinical characteristics and atherosclerosis were assessed. IL-17A, TNF-α, and hs-CRP levels were measured. Results: Psoriasis vulgaris patients with atherosclerosis had higher levels of hs-CRP (median = 1.22; interquartile range-IQR = 0.34-12.11) and IL-17A (median = 1.30; IQR = 0.43-4.28), but a lower level of TNF-α (median = 0.54; IQR = 0.13-3.41) compared to those without atherosclerosis (p < 0.05). Only LogIL-17A was positively related to atherosclerosis in psoriasis patients (Odds Ratio-OR = 2.16, 95% CI = 1.06-4.38, p < 0.05). After excluding systemically treated patients, LogIL-17A and Log TNF-α were associated with the likelihood of atherosclerosis (p < 0.05). Conclusion: This study suggests a link between elevated levels of IL-17A and TNF-α and subclinical atherosclerosis. Further investigation on a larger scale is required to establish the causality of this relationship.

5.
Chem Biodivers ; : e202401934, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187695

RESUMO

From the leaves of Tithonia diversifolia, nine sesquiterpenoids (1-9), including two new ones (tagitinin J (1) and tagitinin K (2)) were isolated and structurally determined. Their chemical structures were elucidated by extensive analyses of the HRESIMS and NMR spectral data, as well as comparison with the literature. All of the isolated compounds (except compounds 7-9) significantly exhibited cytotoxic activity against four human cancer cell lines (KB, HepG2, A549 and MCF7), with IC50 values ranging from 0.29-17.0 µM, which were in the same range as the positive control ellipticine or even lower. Further, the apoptosis induction effects of two new compounds 1 and 2 were also investigated and reported. While compound 2 did not induce the apoptosis in KB cells at test concentrations, compound 1 was found to possess anti-proliferative activity through concentration-dependently inducing cell cycle arrest at S phase, morphological changes, activation of caspase 3, and an increase in the early-stage apoptosis of KB cells at a concentration of 7.26 µM.

6.
J Biomed Opt ; 29(9): 093505, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39050615

RESUMO

Significance: Hyperspectral imaging (HSI) is an emerging imaging modality for oncological applications and can improve cancer detection with digital pathology. Aim: The study aims to highlight the increased accuracy and sensitivity of detecting the margin of thyroid carcinoma in hematoxylin and eosin (H&E)-stained histological slides using HSI and data augmentation methods. Approach: Using an automated microscopic imaging system, we captured 2599 hyperspectral images from 65 H&E-stained human thyroid slides. Images were then preprocessed into 153,906 image patches of dimension 250 × 250 × 84 pixels . We modified the TimeSformer network architecture, which used alternating spectral attention and spatial attention layers. We implemented several data augmentation methods for HSI based on the RandAugment algorithm. We compared the performances of TimeSformer on HSI against the performances of pretrained ConvNext and pretrained vision transformers (ViT) networks on red, green, and blue (RGB) images. Finally, we applied attention unrolling techniques on the trained TimeSformer network to identify the biological features to which the network paid attention. Results: In the testing dataset, TimeSformer achieved an accuracy of 90.87%, a weighted F 1 score of 89.79%, a sensitivity of 91.50%, and an area under the receiving operator characteristic curve (AU-ROC) score of 97.04%. Additionally, TimeSformer produced thyroid carcinoma tumor margins with an average Jaccard score of 0.76 mm. Without data augmentation, TimeSformer achieved an accuracy of 88.23%, a weighted F 1 score of 86.46%, a sensitivity of 85.53%, and an AU-ROC score of 94.94%. In comparison, the ViT network achieved an 89.98% accuracy, an 88.14% weighted F 1 score, an 84.77% sensitivity, and a 96.17% AU-ROC. Our visualization results showed that the network paid attention to biological features. Conclusions: The TimeSformer model trained with hyperspectral histological data consistently outperformed conventional RGB-based models, highlighting the superiority of HSI in this context. Our proposed augmentation methods improved the accuracy, the F 1 score, and the sensitivity score.


Assuntos
Imageamento Hiperespectral , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Imageamento Hiperespectral/métodos , Algoritmos , Microscopia/métodos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Interpretação de Imagem Assistida por Computador/métodos
7.
Orthop Traumatol Surg Res ; : 103932, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38987032

RESUMO

INTRODUCTION: Arthrodesis of the first metatarsophalangeal joint (MTP1) is indicated for hallux rigidus, septic arthritis, severe hallux valgus (HV) or HV revision. Few studies have compared the functional and radiographic outcomes between indications. The goal of this study was to compare the results of MTP1 arthrodesis in patients with severe HV or HV revision at 6 months postoperative. The hypothesis was that there are no differences in the fusion rate, functional scores and radiological correction between the two groups. MATERIALS AND METHODS: This was a retrospective, observational, single-center study conducted between January 1, 2018 and July 31, 2021. The inclusion criteria were patients treated for severe HV or HV revision by MTP1 arthrodesis with a compression screw and locking plate who were at least 18 years of age. The exclusion criteria were a history of septic arthritis of MTP1 without prior HV surgery, primary hallux rigidus, rheumatoid arthritis, incomplete medical record. The functional outcomes consisted of the Foot Function Index (FFi-f) and the European Foot and Ankle Society (EFAS) score. Radiographs were made to evaluate preoperative and postoperative deformity, the correction and the fusion rate. These outcomes were compared between two groups: severe HV and HV revision. RESULTS: An analysis was done of 58 cases of MTP1 arthrodesis: 45 severe HV and 13 HV revisions. The mean patient age was 66 years, and the mean follow-up was 15.7 months. There were no significant differences between the two groups in the postoperative functional scores: EFAS (p = 0.85) and FFI-f (p = 0.14). At the final review, there were no significant differences between the two groups in the foot angle measurements (hallux valgus angle, p = 0.08 and intermetatarsal angle, p = 0.15) and fusion rate (p = 0.89) with a 93% fusion rate in patients with severe HV and 92% in patients with HV revision. CONCLUSION: Given the good radiographic and functional outcomes, MTP1 arthrodesis by locking plate and compression screw is indicated as a first line surgical treatment for patients with severe HV or for patients undergoing HV revision. There is no evidence of a significant difference in the functional scores, fusion rate and radiographic correction between these two indications. LEVEL OF PROOF: IV; retrospective case series.

8.
Interv Neuroradiol ; : 15910199241264342, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39034279

RESUMO

BACKGROUND AND PURPOSE: The acute vertebrobasilar occlusion associated with the poor prognosis, particularly tandem occlusion. However, few data on the efficacy of the endovascular therapy was indicated in this occlusion. We investigated whether the additional rescue extracranial vertebral stenting improved clinical outcome by modified Rankin scale (mRS) score within 3 months after the procedure. METHODS: This was a retrospective analysis of patients with acute posterior tandem occlusion who were treated with rescue extracranial vertebral stenting between December 2020 and January 2024 at our hospital. Clinical, neuroimaging, procedural, and complication data were collected. Primary outcomes included the rate of good outcomes (mRS ≤ 2) at 3-month follow-up. RESULTS: Nine patients who underwent rescue extracranial vertebral stenting in posterior circulation tandem occlusions were enrolled in the study. All patients were achieved the successful recanalization (mTICI ≥ 2b). Of Dotter technique in the "distal-to-proximal" approach, Diagnostic-Dotter made up 66.7%. Five patients (55.6%) with good outcome (mRS ≤ 2) at 3 months, and 1 patient (11.1%) underwent suboccipital decompressive craniectomy due to the malignant cerebellar infarction. CONCLUSION: Our study suggests that despite the small series with posterior tandem occlusions, the rescue extracranial vertebral stenting could be an important alternative treatment followed by mechanical thrombectomy.

9.
J Ethnopharmacol ; 333: 118447, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38885914

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng Radix and Astragali Radix are commonly combined to tonify Qi and alleviate fatigue. Previous studies have employed biological networks to investigate the mechanisms of herb pairs in treating different diseases. However, these studies have only elucidated a single network for each herb pair, without emphasizing the superiority of the herb combination over individual herbs. AIM OF THE STUDY: This study proposes an approach of comparing biological networks to highlight the synergistic effect of the pair in treating cancer-related fatigue (CRF). METHODS: The compounds and targets of Ginseng Radix, Astragali Radix, and CRF diseases were collected and predicted using different databases. Subsequently, the overlapping targets between herbs and disease were imported into the STRING and DAVID tools to build protein-protein interaction (PPI) networks and analyze enriched KEGG pathways. The biological networks of Ginseng Radix and Astragali Radix were compared separately or together using the DyNet application. Molecular docking was used to verify the predicted results. Further, in vitro experiments were conducted to validate the synergistic pathways identified in in silico studies. RESULTS: In the PPI network comparison, the combination created 89 new interactions and an increased average degree (11.260) when compared to single herbs (10.296 and 9.394). The new interactions concentrated on HRAS, STAT3, JUN, and IL6. The topological analysis identified 20 core targets of the combination, including three Ginseng Radix-specific targets, three Astragali Radix-specific targets, and 14 shared targets. In KEGG enrichment analysis, the combination regulated additional signaling pathways (152) more than Ginseng Radix (146) and Astragali Radix (134) alone. The targets of the herb pair synergistically regulated cancer pathways, specifically hypoxia-inducible factor 1 (HIF-1) signaling pathway. In vitro experiments including enzyme-linked immunosorbent assay and Western blot demonstrated that two herbs combination could up-regulate HIF-1α signaling pathway at different combined concentrations compared to either single herb alone. CONCLUSION: The herb pair increased protein interactions and adjusted metabolic pathways more than single herbs. This study provides insights into the combination of Ginseng Radix and Astragali Radix in clinical practice.


Assuntos
Astragalus propinquus , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas , Fadiga , Simulação de Acoplamento Molecular , Neoplasias , Panax , Mapas de Interação de Proteínas , Panax/química , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Neoplasias/tratamento farmacológico , Fadiga/tratamento farmacológico , Astragalus propinquus/química , Astrágalo/química , Transdução de Sinais/efeitos dos fármacos
10.
J Integr Neurosci ; 23(6): 122, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38940090

RESUMO

BACKGROUND: Rheum tanguticum root, cataloged as "Daehwang" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing Daehwang are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of R. tanguticum root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration. METHODS: The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for Daehwang and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms. RESULTS: The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (TNF-α), glial fibrillary acidic protein (GFAP), and c-fos in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of R. tanguticum components in neurodegeneration (p = 4.35 × 10-5) and TNF signaling pathway (p = 9.94 × 10-5). CONCLUSIONS: The in vivo and in silico analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, R. tanguticum root is a promising herbal treatment option for antiepileptic and neuroprotective applications.


Assuntos
Anticonvulsivantes , Modelos Animais de Doenças , Epilepsia , Hipocampo , Fármacos Neuroprotetores , Extratos Vegetais , Raízes de Plantas , Rheum , Compostos de Trimetilestanho , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Rheum/química , Raízes de Plantas/química , Masculino , Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamente , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Simulação por Computador , Farmacologia em Rede , Mapas de Interação de Proteínas , Ratos
11.
Front Med (Lausanne) ; 11: 1345698, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695034

RESUMO

Background: Antimicrobial Stewardship Programs (ASP) have been applied widely in high-resource countries to prevent surgical site infections (SSI). Evidence favoring ASP interventions (ASPi) in gastrointestinal surgeries from low and middle-income countries has been limited, especially in antimicrobial prophylaxis. We aimed to investigate this gap at a Vietnamese tertiary hospital. Methods: We conducted a retrospective cohort study on patients undergoing clean-contaminated surgeries in 2015 who received standard of care (SoC) or SoC + ASPi. Primary outcome was 30-day SSI incidence. Secondary outcomes included length of stay (LoS) after surgery (days), cost of antibiotics, and cost of treatment (USD). Results were controlled for multiplicity and reported with treatment effect and 95% confidence interval (95%CI). A predictive model was built and cross-validated to detect patients at high risk of SSI. Results: We included 395 patients for analysis (48.1% being female, mean age 49.4 years). Compared to patients receiving SoC, those with SoC + ASPi had a lower incidence of 30-day SSI (-8.8, 95%CI: -16.0 to -1.6, p = 0.042), shorter LoS after surgery (-1.1 days, 95%CI: -1.8 to -0.4, p = 0.004), and lower cost of antibiotics (-37.3 USD, 95%CI: -59.8 to -14.8, p = 0.012) and treatment (-191.1 USD, 95%CI: -348.4 to -33.8, p = 0.042). We estimated that by detecting patients at high risk of SSI with the predictive model and providing prophylactic measures, we could save 398120.7 USD per 1,000 cases of SSI. Conclusion: We found that ASPi were associated with a reduction in risks of SSI, hospital stays, and cost of antibiotics/treatment in a Vietnamese tertiary hospital.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38707637

RESUMO

During surgery of delicate regions, differentiation between nerve and surrounding tissue is crucial. Hyperspectral imaging (HSI) techniques can enhance the contrast between types of tissue beyond what the human eye can differentiate. Whereas an RGB image captures 3 bands within the visible light range (e.g., 400 nm to 700 nm), HSI can acquire many bands in wavelength increments that highlight regions of an image across a wavelength spectrum. We developed a workflow to identify nerve tissues from other similar tissues such as fat, bone, and muscle. Our workflow uses spectral angle mapper (SAM) and endmember selection. The method is robust for different types of environment and lighting conditions. We validated our workflow on two samples of human tissues. We used a compact HSI system that can image from 400 to 1700 nm to produce HSI of the samples. On these two samples, we achieved an intersection-over-union (IoU) segmentation score of 84.15% and 76.73%, respectively. We showed that our workflow identifies nerve segments that are not easily seen in RGB images. This method is fast, does not rely on special hardware, and can be applied in real time. The hyperspectral imaging and nerve detection approach may provide a powerful tool for image-guided surgery.

13.
J Imaging Inform Med ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809338

RESUMO

The diagnosis and treatment of vocal fold disorders heavily rely on the use of laryngoscopy. A comprehensive vocal fold diagnosis requires accurate identification of crucial anatomical structures and potential lesions during laryngoscopy observation. However, existing approaches have yet to explore the joint optimization of the decision-making process, including object detection and image classification tasks simultaneously. In this study, we provide a new dataset, VoFoCD, with 1724 laryngology images designed explicitly for object detection and image classification in laryngoscopy images. Images in the VoFoCD dataset are categorized into four classes and comprise six glottic object types. Moreover, we propose a novel Multitask Efficient trAnsformer network for Laryngoscopy (MEAL) to classify vocal fold images and detect glottic landmarks and lesions. To further facilitate interpretability for clinicians, MEAL provides attention maps to visualize important learned regions for explainable artificial intelligence results toward supporting clinical decision-making. We also analyze our model's effectiveness in simulated clinical scenarios where shaking of the laryngoscopy process occurs. The proposed model demonstrates outstanding performance on our VoFoCD dataset. The accuracy for image classification and mean average precision at an intersection over a union threshold of 0.5 (mAP50) for object detection are 0.951 and 0.874, respectively. Our MEAL method integrates global knowledge, encompassing general laryngoscopy image classification, into local features, which refer to distinct anatomical regions of the vocal fold, particularly abnormal regions, including benign and malignant lesions. Our contribution can effectively aid laryngologists in identifying benign or malignant lesions of vocal folds and classifying images in the laryngeal endoscopy process visually.

14.
Ther Adv Med Oncol ; 16: 17588359241242972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736554

RESUMO

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X-S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X-S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38729389

RESUMO

BACKGROUND & AIMS: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD). METHODS: From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature.

16.
Int J Biol Macromol ; 266(Pt 1): 131038, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518931

RESUMO

Aqueous solutions of alginate (4 %) with or without hydrogen peroxide (0-2 % H2O2) were irradiated under a gamma Co-60 source. The effect of dose rate on the radiation scission yield (Gs) of resulting irradiated alginate was determined. At the dose of 20 kGy, the G(s) value of irradiated alginate decreased with the increase dose rate, suggesting that the irradiation at a suitable dose rate could further improve the radiation chemical yield of degradation. For the alginate irradiated at the same dose rate, G(s) value increased with the increase of H2O2 concentration. Average molecular weight (Mw) and polydispersity index (PI) of irradiated alginate rapidly decreased with the increase in dose and further decreased by addition of H2O2. The oligoalginate with Mw ~ 9800 g/mol was obtained by radiation degradation of 4 % alginate solution containing 2 % H2O2 at dose of 20 kGy. Radiation scission of glycoside bonds and formation of carbonyl groups (C=O) were indicated in UV and FTIR spectra of irradiated alginate. Peanut seedlings were fertilized with alginate and oligoalginate solutions, and the results showed that all growth parameters of the treated plants were better than those of the control. Furthermore, the oligoalginate prepared by gamma irradiation can be applied as a plant growth promoter for agriculture production.


Assuntos
Alginatos , Arachis , Raios gama , Peróxido de Hidrogênio , Peso Molecular , Alginatos/química , Arachis/química , Arachis/efeitos da radiação , Peróxido de Hidrogênio/química , Relação Dose-Resposta à Radiação
17.
Eur J Orthop Surg Traumatol ; 34(4): 1893-1899, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38451337

RESUMO

PURPOSE: Rotational malalignment and leg length discrepancy after intramedullary nailing of femoral shaft are frequent. This study has three objectives: evaluate the rate of femoral rotational malalignment and leg length discrepancy using EOS imaging after antegrade intramedullary nailing of femoral shaft fracture, find a relevant clinical examination to detect malrotation and identified risk factors. METHODS: We performed a retrospective single-centre study between January 2014 and January 2022. Fifty-eight patients were clinically and radiographically assessed at a minimum of three months. RESULTS: The femoral rotation of the operated side was significantly greater by a mean of 15.4° in internal rotation compared to the healthy side. There was no statically significant difference for the femoral length (p = 0.08). CONCLUSION: When using EOS stereography following antegrade intramedullary nailing of post-traumatic diaphyseal femur fractures, a statistically significant difference of more than 15.4° in internal rotation was found for femoral rotation on the operated side compared to the healthy side.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [B. Poirot] Last name [Seynaeve]. Also, kindly confirm the details in the metadata are correct.The last name of the first author was corrected : Given name = B. and last name = Poirot Seynaeve The details in matadata are correct LEVEL OF EVIDENCE: III.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Humanos , Fixação Intramedular de Fraturas/métodos , Fixação Intramedular de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/instrumentação , Fraturas do Fêmur/cirurgia , Fraturas do Fêmur/diagnóstico por imagem , Estudos Retrospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Rotação , Desigualdade de Membros Inferiores/etiologia , Desigualdade de Membros Inferiores/diagnóstico por imagem , Fraturas Mal-Unidas/diagnóstico por imagem , Fraturas Mal-Unidas/cirurgia , Imageamento Tridimensional/métodos , Adulto Jovem , Mau Alinhamento Ósseo/diagnóstico por imagem , Mau Alinhamento Ósseo/etiologia , Idoso , Fêmur/diagnóstico por imagem , Fêmur/cirurgia
18.
CVIR Endovasc ; 7(1): 25, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441744

RESUMO

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is the most severe clinical form of peripheral artery disease (PAD), accounting for approximately 11%, and is strongly associated with the incidence of amputation, cardiovascular events, and mortality. The Global Vascular Guideline (GVG) proposed a new Global Anatomic Staging System (GLASS) for evaluating the anatomic complexity of arterial lesions. However, more research is required to evaluate outcomes after endovascular intervention in CLTI patients using the GLASS. OBJECTIVE: Our study aimed to describe clinical characteristics, arterial lesions, and endovascular interventions according to three grades of GLASS in the Vietnamese population. We evaluated the technical success, mortality rate, and probability to preserve the limb according to the GLASS. METHODS: All patients were diagnosed with CLTI and underwent infrainguinal endovascular intervention at the Department of Thoracic and Vascular Surgery, University Medical Center, Ho Chi Minh City from June 2020 to June 2022. All patients were evaluated before intervention and follow-up at 6 and 12 months after intervention. Patients were divided into three groups according to the GLASS, thereby comparing the technical success, mortality, and amputation rates. This retrospective study describes a series of cases. RESULTS: The study sample evaluated 82 lower limbs of 82 patients, in which GLASS class I, II, and III lesions accounted for 36.6%, 43.9%, and 19.5% of the patients, respectively. The rates of technical success in the groups gradually decreased according to the complexity of the lesions (90%, 86.11%, and 56.25% for GLASS I, II, and III, respectively; p = 0.012). Notably, limb-based patency (LBP) at 12 months was significantly lower in the GLASS III group than in the GLASS I and II groups (22.22% vs 88.89% and 67.74%, respectively; p = 0.001). The amputation rates at 12 months in GLASS groups I, II, and III were 13.3%, 22.2%, and 50%, respectively (p = 0.021), while the mortality rates at 12 months were 0%, 8.33%, and 25%, respectively (p = 0.015). CONCLUSION: In patients with CLTI of higher GLASS stages, the rates of technical success were lower and the amputation and mortality rates were higher.

19.
BMC Cancer ; 24(1): 176, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317094

RESUMO

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.


Assuntos
Afatinib , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Afatinib/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Vietnã/epidemiologia
20.
Scand J Gastroenterol ; 59(5): 553-560, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38353236

RESUMO

BACKGROUND: Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR. METHODS: We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated. RESULTS: From 2005 to 2020, 27 patients (Crohn's Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first (n = 2), second (n = 4) or third (n = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX. CONCLUSION: IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics.What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation.What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity.How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade a Drogas , Fármacos Gastrointestinais , Doenças Inflamatórias Intestinais , Infliximab , Humanos , Infliximab/uso terapêutico , Infliximab/administração & dosagem , Infliximab/imunologia , Infliximab/efeitos adversos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/etiologia , Pessoa de Meia-Idade , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/imunologia , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Resultado do Tratamento , Adulto Jovem
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