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Low flexural strength and toughness have posed enduring challenges to cementitious materials. As the main hydration product of cement, calcium silicate hydrate (C-S-H) plays important roles in the mechanical performance of cementitious materials while exhibiting random microstructures with pores and defects, which hinder mechanical enhancement. Inspired by the "brick-and-mortar" microstructure of natural nacre, this paper presents a method combining freeze casting, freeze-drying, in situ polymerization, and hot pressing to fabricate C-S-H nacre with high flexural strength, high toughness, and lightweight. Poly(acrylamide-co-acrylic acid) was used to disperse C-S-H and toughen C-S-H building blocks, which function as "bricks", while poly(methyl methacrylate) was impregnated as "mortar". The flexural strength, toughness, and density of C-S-H nacre reached 124 MPa, 5173 kJ/m3, and 0.98 g/cm3, respectively. The flexural strength and toughness of the C-S-H nacre are 18 and 1230 times higher than those of cement paste, respectively, with a 60% reduction in density, outperforming existing cementitious materials and natural nacre. This research establishes the relationship between material composition, fabrication process, microstructure, and mechanical performance, facilitating the design of high-performance C-S-H-based and cement-based composites for scalable engineering applications.
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Glabridin (Gla) has been reported to have significant effects in scar treatment, and however, the water insolubility of Gla leads to its poor transdermal absorption ability, which affects its bioactivities. Therefore, we attempted to prepare the Gla dissolving microneedles (Gla-MN) to improve the absorbtion of Gla. After investigation of the 3 factors including the needle tip matrix concentration, the prescription concentration of backing material, and the dissolution method of Gla, we finally determined the process parameters of 10% hyaluronic acid (HA) as the needle tip and 5% polyvinyl alcohol (PVA) as the backing, according to which the Gla-MN was prepared with the good characteristics of high hardness, complete appearance and good in vitro dissolution ability. We then loaded Gla onto the microneedles and measured that the average drug loading of Gla-MN was 2.26 ± 0.11 µg/mg and the cumulative transdermal release of Gla-MN was up to 76.9% after 24 h. In addition, Gla-MN had good skin penetration properties, with Gla-MN penetrating at least 4 to 5 layers of parafilm. And the skin basically could return to normal after 4 h of piercing. Importantly, our results showed that Gla-MN had higher transdermal delivery and therapeutic effects against keloid than that of Gla at the same dosage.
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BACKGROUND: The fractures of patients with osteoporosis represent a major health care burden that requires efficient prevention. OBJECTIVE: To analyze the efficacy and significance of diverse interventions for preventing falls or fractures in patients with osteoporosis, and to establish a foundation for clinical interventions. METHODS: Ten databases were searched for studies published before January 30, 2024. Screening, data extraction, and risk of bias assessment were independently conducted by two researchers using Stata 14.0 software. A network meta-analysis using the frequentist framework was then performed to determine the effectiveness of various interventions for preventing and managing falls and fractures in patients with osteoporosis. The findings were used as basis for the prioritization of interventions. RESULTS: The initial search yielded 3894 studies. After 3878 studies were excluded, 16 studies were finally included. For the prevention of falls in patients with osteoporosis, effective interventions include exercise and exercise plus medication. A combination of exercise, assessment and modifications, quality improvement strategies, social engagement, basic falls risk assessment, and assistive technology may be the preferred recommended intervention. For the prevention of fractures in patients with osteoporosis, no statistically significant disparities were observed among the compared interventions, exercise may be the preferred recommended intervention. CONCLUSION: Exercise and exercise plus medication are effective in reducing the number of falls in patients with osteoporosis. Although exercise may be the optimal intervention for fracture prevention, the quality of current evidence remains inadequate. Large-scale high-quality randomized controlled trials are necessary to substantiate these findings. TRIAL REGISTRATION: PROSPERO CRD42024507487.
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.
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Pró-Proteína Convertase 9 , Humanos , Pró-Proteína Convertase 9/metabolismo , Pró-Proteína Convertase 9/imunologia , Células Hep G2 , Inibidores de PCSK9 , Ressonância de Plasmônio de Superfície , Receptores de LDL/metabolismo , Epitopos/imunologia , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/imunologiaRESUMO
Since there is insufficient evidence to determine the best treatment of transurethral laser lithotripsy (TLL) in ureteral stones, this study compared the effectiveness and safety of TLL using high-power (HP) (100 W) and low-power (LP) (20 W) laser settings. All patients with maximally sized ureteral stones who were planned for transurethral holmium laser lithotripsy were enrolled in this open study. One of the two laser setting groups-LP or HP-was allocated to each alternate patient. Using IBM SPSS Statistics 24, the treatment groups were compared for operating time, intraoperative and postoperative problems (up to 1 year), and rates of stone-free recovery. Welch tests were employed to compare continuous data, whereas Fisher's exact or Chi-square tests were used to assess categorical variables. At P < 0.05, statistical significance was established. A total of 207 individuals were included and preoperative data were comparable between the two groups. The HP group had a considerably greater ablation rate and a significantly shorter procedure duration (42.61 ± 11.74 min) than the LP group (78.56 ± 25.91 min) ( P = 0.025). The Overactive Bladder Symptom Score and International Prostate Symptom Score were considerably higher in the HP group than in the LP group. Treatment effectiveness was considerably impacted by the location of the ureteral stone, according to univariate and multivariate logistic regression models. A HP laser setting of up to 100 W greatly shortens the duration of the process for treating ureteral stones without raising the risk of problems.
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Lasers de Estado Sólido , Litotripsia a Laser , Cálculos Ureterais , Humanos , Cálculos Ureterais/terapia , Masculino , Litotripsia a Laser/métodos , Feminino , Lasers de Estado Sólido/uso terapêutico , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , IdosoRESUMO
Joint source-channel coding (JSCC) based on deep learning has shown significant advancements in image transmission tasks. However, previous channel-adaptive JSCC methods often rely on the signal-to-noise ratio (SNR) of the current channel for encoding, which overlooks the neural network's self-adaptive capability across varying SNRs. This paper investigates the self-adaptive capability of deep learning-based JSCC models to dynamically changing channels and introduces a novel method named Channel-Blind JSCC (CBJSCC). CBJSCC leverages the intrinsic learning capability of neural networks to self-adapt to dynamic channels and diverse SNRs without relying on external SNR information. This approach is advantageous, as it is not affected by channel estimation errors and can be applied to one-to-many wireless communication scenarios. To enhance the performance of JSCC tasks, the CBJSCC model employs a specially designed encoder-decoder. Experimental results show that CBJSCC outperforms existing channel-adaptive JSCC methods that depend on SNR estimation and feedback, both in additive white Gaussian noise environments and under slow Rayleigh fading channel conditions. Through a comprehensive analysis of the model's performance, we further validate the robustness and adaptability of this strategy across different application scenarios, with the experimental results providing strong evidence to support this claim.
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Mibavademab (previously known as REGN4461), a fully human monoclonal antibody, is being investigated for the treatment of conditions associated with leptin deficiency. Here, we report pharmacokinetics (PKs), pharmacodynamics, and immunogenicity from a phase I study in healthy participants (NCT03530514). In part A, lean or overweight healthy participants were randomized to single-ascending-dose cohorts of 0.3, 1.0, 3.0, 10, and 30 mg/kg intravenous (i.v.), or 300 and 600 mg subcutaneous doses of mibavademab or placebo. In part B, overweight or obese participants were randomized to receive multiple doses of mibavademab (15 mg/kg i.v. loading dose and 10 mg/kg i.v. at weeks 3, 6, and 9) or placebo, stratified by body mass index and baseline leptin levels: low leptin (<5 ng/mL) or relatively low leptin (5-8 ng/mL in men and 5-24 ng/mL in women). Fifty-six and 55 participants completed the single-ascending-dose and multiple-dose parts, respectively. In the single-ascending-dose cohorts, mibavademab PKs were nonlinear with target-mediated elimination, greater than dose-proportional increases in exposure, and there were no dose-dependent differences in total soluble leptin receptor (sLEPR) levels in serum over time. Following multiple-dose administration of mibavademab in participants with leptin <8 ng/mL, lower mean mibavademab concentrations, higher mean total sLEPR concentrations, and larger mean decreases in body weight than in the relatively low leptin cohorts were observed. Baseline leptin was correlated with mibavademab PKs and pharmacodynamics. No treatment-emergent anti-mibavademab antibodies were observed in any mibavademab-treated participant. Results from this study collectively inform further development of mibavademab to treat conditions associated with leptin deficiency.
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Leptina , Sobrepeso , Masculino , Humanos , Feminino , Leptina/farmacocinética , Leptina/uso terapêutico , Receptores para Leptina/uso terapêutico , Obesidade/tratamento farmacológico , Índice de Massa Corporal , Método Duplo-CegoRESUMO
In eukaryotic cells, transcription, translation, and mRNA degradation occur in distinct subcellular regions. How these mRNA processes are organized in bacteria, without employing membrane-bound compartments, remains unclear. Here, we present generalizable principles underlying coordination between these processes in bacteria. In Escherichia coli, we found that co-transcriptional degradation is rare for mRNAs except for those encoding inner membrane proteins, due to membrane localization of the main ribonuclease, RNase E. We further found, by varying ribosome binding sequences, that translation affects mRNA stability not because ribosomes protect mRNA from degradation, but because low translation leads to premature transcription termination in the absence of transcription-translation coupling. Extending our analyses to Bacillus subtilis and Caulobacter crescentus, we established subcellular localization of RNase E (or its homolog) and premature transcription termination in the absence of transcription-translation coupling as key determinants that explain differences in transcriptional and translational coupling to mRNA degradation across genes and species.
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Microplastics have been detected from water and soil systems extensively, with increasing evidence indicating their detrimental impacts on human and animal health. Concerns surrounding microplastic pollution have spurred the development of advanced collection and characterization methods for studying the size, abundance, distribution, chemical composition, and environmental impacts. This paper offers a comprehensive review of artificial intelligence (AI)-empowered technologies for the collection and characterization of microplastics. A framework is presented to streamline efforts in utilizing emerging robotics and machine learning technologies for collecting, processing, and characterizing microplastics. The review encompasses a range of AI technologies, delineating their principles, strengths, limitations, representative applications, and technology readiness levels, facilitating the selection of suitable AI technologies for mitigating microplastic pollution. New opportunities for future research and development on integrating robots and machine learning technologies are discussed to facilitate future efforts for mitigating microplastic pollution and advancing AI technologies.
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The development of unconventional long-wavelength fluorescent polymer hydrogels without using polycyclic aromatic hydrocarbons or extended π-conjugation is a fundamental challenge in luminescent materials owing to a lack of understanding regarding the spatial interactions induced inherent clustering-triggered emission under water-rich conditions. Inspired by the color change of protein astaxanthin as a result of heat-induced denaturation, we propose a thermodynamically driven strategy to develop red fluorescence (~610 nm) by boiling multiple hydrogen-bonded poly(N-acryloylsemicarbazide) hydrogels in a water bath. We reveal that thermodynamically driven conformational changes of polymer chains from isolated hydrogen bonding donor-acceptor structures to through-space interaction structures induce intrinsic fluorescence shifts from blue to red during clustering-triggered emission. The proposed multiple hydrogen-bonding supramolecular hydrogel shows good fluorescence stability, mechanical robustness, and 3D printability for customizable shaping. We provide a viable method to prepare nonconventional long-wavelength fluorescent hydrogels towards soft fluorescent devices without initially introducing any fluorescent components.
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Background: Ustekinumab (UST) is approved as an effective therapy for Crohn's disease (CD) in adults. Off-label use is increasing in the pediatric population, more data on safety and efficacy in pediatric patients with CD is urgently needed. Aims: This study aimed to evaluate the clinical efficacy and safety of UST in children and adolescents with Crohn's disease. Methods: This multicenter retrospective study carried out at three tertiary care centers, and identified children who received their first dose of UST at 18 years old or younger and followed up for a minimum of 24 weeks. Data on demographics, disease behavior, location and activity, treatment history were collected. The primary outcomes were clinical remission at weeks 24-32 and weeks 48-56 of UST therapy. Secondary outcomes were clinical response at the same time points, endoscopic remission, changes in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin and fecal calprotectin, improvement in growth parameters, and rate of adverse events. Results: Sixteen patients were included, and 11/13 (84.6%) continued to receive UST after 1 year. Our data demonstrate that the clinical remission rates were 41.7% at weeks 24â¼32 with the Weighted pediatric CD activity index (wPCDAI) was lower than baseline (43.8, IQR: 31.3-51.9 vs.15, IQR: 5.6-25, p < 0.001) and 75% at weeks 48-56 with wPCDAI was lower than baseline (42.5, IQR: 23.8-50 vs. 7.5, IQR: 0-13.8, p = 0.004). Five of eleven children achieved endoscopic remission. No serious adverse events were recorded during the study period. Conclusions: UST is efficacious and safe in pediatric patients with CD. Pediatric patients could benefit from UST as either a primary or secondary biologic therapy for the induction, or maintenance of remission of CD.
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PURPOSE: Interleukin-10 receptor (IL-10R) deficiency can result in life-threatening very early-onset inflammatory bowel disease (VEO-IBD). Umbilical cord blood transplantation (UCBT) is a curative therapy for patients with IL-10R deficiency. This study aimed to investigate the efficacy of UCBT in treating IL-10R deficiency and develop a predictive model based on pre-transplant factors. METHODS: Eighty patients with IL-10R deficiency who underwent UCBT between July 2015 and April 2023 were retrospectively analyzed. Cox proportional hazards regression and random survival forest were used to develop a predictive model. RESULTS: Median age at transplant was 13.0 months (interquartile range [IQR], 8.8-25.3 months). With a median follow-up time of 29.4 months (IQR, 3.2-57.1 months), the overall survival (OS) rate was 65.0% (95% confidence interval [CI], 55.3%-76.3%). The engraftment rate was 85% (95% CI, 77%-93%). The cumulative incidences of acute and chronic graft-versus-host disease were 48.2% (95% CI, 37.1%-59.4%) and 12.2% (95% CI, 4.7%-19.8%), respectively. VEO-IBD-associated clinical symptoms were resolved in all survivors. The multivariate analysis showed that IL-6 and stool occult blood were independent prognostic risk factors. The multivariate Cox proportional hazards regression model with stool occult blood, length- or height-for-age Z-score, medical history of sepsis, and cord blood total nucleated cells showed good discrimination ability, with a bootstrap concordance index of 0.767-0.775 in predicting OS. CONCLUSION: Better inflammation control before transplantation and higher cord blood total nucleated cell levels can improve patient prognosis. The nomogram can successfully predict OS in patients with IL-10R deficiency undergoing UCBT.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Doenças Inflamatórias Intestinais , Humanos , Lactente , Pré-Escolar , Estudos Retrospectivos , Receptores de Interleucina-10 , Doenças Inflamatórias Intestinais/diagnósticoRESUMO
OBJECTIVE: This study used random forest model to explore the feasibility of radial artery calcification in prediction of coronary artery calcification in hemodialysis patients. MATERIAL AND METHODS: We enrolled hemodialysis patients and performed ultrasound examinations on their radial arteries to evaluate the calcification status using a calcification index. All involved patients received coronary artery computed tomography scans to generate coronary artery calcification scores (CACS). Clinical variables were collected from all patients. We constructed both a random forest model and a logistic regression model to predict CACS. Logistic regression model was used to identify the risk factors of radial artery calcification. RESULTS: One hundred eighteen patients were included in our analysis. In random forest model, the radial artery calcification index, age, serum C-reactive protein, body mass index (BMI), diabetes, and hypertension history were related to CACS based on the average decrease of the Gini coefficient. The random forest model achieved a sensitivity of 76.9%, specificity of 75.0%, and area under receiver operating characteristic of 0.869, while the logistic regression model achieved a sensitivity of 75.2%, specificity of 68.7%, and area under receiver operating characteristic of 0.742 in prediction of CACS. Sex, BMI index, smoking history, hypertension history, diabetes history, and serum total calcium were all the risk factors related to radial artery calcification. CONCLUSIONS: A random forest model based on radial artery calcification could be used to predict CACS in hemodialysis patients, providing a potential method for rapid screening and prediction of coronary artery calcification.
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Doença da Artéria Coronariana , Aprendizado Profundo , Artéria Radial , Diálise Renal , Calcificação Vascular , Humanos , Masculino , Feminino , Diálise Renal/efeitos adversos , Artéria Radial/diagnóstico por imagem , Pessoa de Meia-Idade , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etiologia , Calcificação Vascular/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Idoso , Fatores de Risco , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Valor Preditivo dos TestesRESUMO
Four new nortriterpenoid alkaloids, namely buxrugulines E-H (1-4), along with five known ones (5-9), were isolated from the twigs and leaves of Buxus rugulosa. Their structures were identified based on extensive NMR data and MS spectroscopic analyses. Our bioassays revealed that compounds 5, 6 and 8 exhibited potent cytotoxicity in vitro against MCF-7 cell lines, with IC50 values ranging from 6.70 to 11.00 µM, respectively.
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Alcaloides , Buxus , Triterpenos , Humanos , Buxus/química , Triterpenos/farmacologia , Triterpenos/química , Alcaloides/farmacologia , Alcaloides/química , Células MCF-7 , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
BACKGROUND: Keloid (KL) is a common benign skin tumor. KL is typically characterized by significant fibrosis and an intensive inflammatory response. Therefore, a comprehensive understanding of the interactions between cellular inflammation and fibrotic cells is essential to elucidate the mechanisms driving the progression of KL and to develop therapeutics. OBJECTIVE: Investigate the transcriptome landscape of inflammation and fibrosis in keloid scars. METHODS: In this paper, we performed transcriptome sequencing and microRNA (miRNA) sequencing on unselected live cells from six human keloid tissues and normal skin tissues to elucidate a comprehensive transcriptome landscape. In addition, we used single-cell RNA sequencing (scRNA-seq) analysis to analyze intercellular communication networks and enrich fibroblast populations in two additional keloid and normal skin samples to study fibroblast diversity. RESULTS: By RNA sequencing and a miRNA-mRNA-PPI network analysis, we identified miR-615-5p and miR-122b-3p as possible miRNAs associated with keloids, as they differed most significantly in keloids. Similarly, COL3A1, COL1A2, THBS2, TNC, IGTA, THBS4, TGFB3 as genes with significant differences in keloid may be associated with keloid development. Using single-cell RNA sequencing data from 24,086 cells collected from normal or keloid, we report reconstructed intercellular signaling network analysis and aggregation to modules associated with specific cell subpopulations at the cellular level for keloid alterations. CONCLUSIONS: Our multitranscriptomic dataset delineates inflammatory and fibro heterogeneity of human keloids, underlining the importance of intercellular crosstalk between inflammatory cells and fibro cells and revealing potential therapeutic targets.
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Queloide , MicroRNAs , Humanos , Queloide/genética , Queloide/patologia , Transcriptoma , MicroRNAs/genética , Perfilação da Expressão Gênica , Fibroblastos/patologia , Inflamação/genética , Inflamação/patologiaRESUMO
BACKGROUND AND AIMS: Objective evaluation of treatment response is critical in the management of Crohn's disease (CD). Compared with endoscopy, intestinal ultrasound (IUS) is non-invasive and well-tolerated. This study is aimed to assess the predictive value of IUS score for treatment response in pediatric CD patients. METHODS: We conducted a retrospective study in pediatric CD patients who underwent endoscopy and IUS at start of infliximab treatment [T0] and after 22-38 weeks [T1] between February 2021 and January 2023. Pediatric Crohn's Disease Activity Index (PCDAI), biochemical parameters, the Simple Endoscopic Score for Crohn's disease (SES-CD) and IUS parameters were collected at two timepoints. IUS scores were assessed by International Bowel Ultrasound Segment Activity Score (IBUS-SAS). RESULTS: Thirty patients were included, with 53.3% reaching endoscopic response and 43.3% endoscopic remission. After infliximab treatment, IBUS-SAS (58.5 ± 24.2 vs 34.4 ± 21.6, p = .0001) was significantly decreased. At T1, change in IBUS-SAS (-38.2 ± 22.0 vs -7.9 ± 24.1, p = .0015) were pronounced in patients with endoscopic response compared with endoscopic non-response. Significant correlation were observed between IBUS-SAS and SES-CD, PCDAI, C-reaction protein, erythrocyte sedimentation rate, hemoglobin, albumin. The most accurate cutoff values for predicting endoscopic response were 57.4% decrease of IBUS-SAS (AUROC: 0.862, p < .001). The optimal cut-off of IBUS-SAS to correlate endoscopic remission was 26.0 (AUROC: 0.686, p = .017). CONCLUSIONS: The validated ultrasound-base score, IBUS-SAS is an effective index for monitoring endoscopic response to infliximab therapy in CD. IUS evaluation could guide treatment decision for pediatric CD.
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Doença de Crohn , Humanos , Criança , Infliximab/uso terapêutico , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Here, we report the clinical pharmacology data from LUMINA-1 (NCT03188666), a Phase 2 trial that evaluated garetosmab (a monoclonal antibody against activin A) in patients with fibrodysplasia ossificans progressiva. Forty-four patients were randomly assigned to intravenous 10 mg/kg of garetosmab or placebo every 4 weeks in a double-blind 28-week treatment period, followed by a 28-week open-label treatment period with garetosmab, and subsequent open-label extension. Serum samples were obtained to assess pharmacokinetics (PK), immunogenicity, and bone morphogenetic protein 9 (BMP9). Comparative exposure-response analyses for efficacy and safety were performed with trough concentrations (Ctrough ) of garetosmab prior to dosing. Steady-state PK was reached 12-16 weeks after the first dose of garetosmab, with mean (standard deviation) Ctrough of 105 ± 30.8 mg/L. Immunogenicity assessments showed anti-garetosmab antibody formation in 1 patient (1/43; 2.3%); titers were low, and did not affect PK or clinical efficacy. Median concentrations of BMP9 in serum were approximately 40 pg/mL at baseline. There were no meaningful differences in PK or BMP9 concentration-time profiles between patients who did and did not experience epistaxis or death. The comparative exposure-response analyses demonstrated no association between Ctrough and efficacy or safety. PK findings were consistent with prior data in healthy volunteers and were typical for a monoclonal antibody administered at doses sufficient to saturate target-mediated clearance. There were no trends that suggested patients with higher serum exposures to garetosmab were more likely to experience a reduction in heterotopic ossification or adverse events. Garetosmab is being further evaluated in the Phase 3 OPTIMA trial.
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Miosite Ossificante , Farmacologia Clínica , Humanos , Miosite Ossificante/tratamento farmacológico , Miosite Ossificante/metabolismo , Anticorpos Monoclonais/efeitos adversosRESUMO
BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) is associated with a unique disease course and distinct endoscopic features. AIMS: This study aims to provide a comprehensive description of the endoscopic and histologic features observed in a large cohort of patients with VEOIBD from a tertiary medical center. METHODS: A retrospective review of medical records from 2011 to 2021 was conducted to analyze clinical data, including disease phenotypes, endoscopic and histologic findings. Next generation sequencing was performed. RESULTS: A total of 225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 patients. Monogenic IBD patients more commonly had CD-like disease. Colonic involvement was more prevalent among those with monogenic IBD (P<0.001). Pseudo-polyps were significantly more common in the monogenic IBD group (P<0.001), while ileal edema and ulcers were significantly more prevalent in non-monogenic IBD cases. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while patients with TNFAIP3 mutations demonstrated both upper and lower gastrointestinal tract involvement. The non-monogenic IBD patients showed a higher incidence of chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration. CONCLUSIONS: Endoscopic and histologic analysis of children with VEOIBD plays a crucial role in facilitating accurate diagnosis. Various forms of monogenic IBD exhibit distinct endoscopic and pathologic changes.
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Doenças Inflamatórias Intestinais , Pólipos , Criança , Humanos , Doenças Inflamatórias Intestinais/complicações , Úlcera/patologia , Colo/patologia , Endoscopia , FenótipoRESUMO
BACKGROUND: Very early-onset inflammatory bowel disease (VEOIBD) with interleukin-10 (IL10R) signaling deficiency usually requires enterostomy in patients who are refractory to traditional treatment. This study aimed to evaluate long-term outcomes after enterostomy for VEOIBD patients with IL10R signaling deficiency. METHODS: The medical records of all patients undergoing enterostomy for signaling deficiency were retrospectively assessed during 2012.1-2022.7 in a tertiary teaching hospital, Children's Hospital of Fudan University, Shanghai, China. Data on disease history, diagnosis and details of enterostomy and stoma closure and follow-up were collected. Univariate and multivariate logistic regression analyses were used to evaluate the risk factors associated with the long-term outcome of delayed stoma closure. RESULTS: A total of 46 patients underwent an enterostomy, 19 who required emergency enterostomy and 27 with selective enterostomy. After ten years of follow-up, 35 patients underwent hematopoietic stem cell transplantation (HSCT), and 25 patients were alive after HSCT. The median timeframe between HSCT and stoma closure was 19.6 [15.9,26.2] months. Nineteen patients underwent stoma closure and had an average age of 3.9 ± 1.5 years; 6 patients were waiting for stoma closure. Based on a univariate logistic model, risk factors significantly associated with late stoma closure were age at enterostomy and age at HSCT. However, multivariate logistic regression showed no statistically significant factor associated with late stoma closure. There was no significant difference between the stoma closure group and delay closure group in the z scores of weight for age at follow up. CONCLUSIONS: This study determined the long-term outcomes after enterostomy for VEOIBD with interleukin-10 signaling deficiency. The appropriate time point of enterostomy and HSCT may improve quality of life in the long term.