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Simultaneous spatial mapping of the activity of multiple enzymes in a living system can elucidate their functions in health and disease. However, methods based on monitoring fluorescent substrates are limited. Here, we report the development of nitrile (C≡N)-tagged enzyme activity reporters, named nitrile chameleons, for the peak shift between substrate and product. To image these reporters in real time, we developed a laser-scanning mid-infrared photothermal imaging system capable of imaging the enzymatic substrates and products at a resolution of 300 nm. We show that when combined, these tools can map the activity distribution of different enzymes and measure their relative catalytic efficiency in living systems such as cancer cells, Caenorhabditis elegans, and brain tissues, and can be used to directly visualize caspase-phosphatase interactions during apoptosis. Our method is generally applicable to a broad category of enzymes and will enable new analyses of enzymes in their native context.
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Diagnóstico por Imagem , Nitrilas , CorantesRESUMO
Biological regulation often depends on reversible reactions such as phosphorylation, acylation, methylation, and glycosylation, but rarely halogenation. A notable exception is the iodination and deiodination of thyroid hormones. Here, we report detection of bromotyrosine and its subsequent debromination during Drosophila spermatogenesis. Bromotyrosine is not evident when Drosophila express a native flavin-dependent dehalogenase that is homologous to the enzyme responsible for iodide salvage from iodotyrosine in mammals. Deletion or suppression of the dehalogenase-encoding condet (cdt) gene in Drosophila allows bromotyrosine to accumulate with no detectable chloro- or iodotyrosine. The presence of bromotyrosine in the cdt mutant males disrupts sperm individualization and results in decreased fertility. Transgenic expression of the cdt gene in late-staged germ cells rescues this defect and enhances tolerance of male flies to bromotyrosine. These results are consistent with reversible halogenation affecting Drosophila spermatogenesis in a process that had previously eluded metabolomic, proteomic, and genomic analyses.
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Proteínas de Drosophila , Fertilidade , Espermatogênese , Tirosina , Animais , Masculino , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Tirosina/metabolismo , Tirosina/análogos & derivados , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Drosophila/genética , Drosophila/metabolismo , Animais Geneticamente Modificados , Hidrolases/metabolismo , Hidrolases/genéticaRESUMO
Schelling's 1971 work on the dynamics of segregation showed that even a small degree of homophily, the desire to live among like neighbors, can lead to a starkly segregated population. One of the driving factors for this result is that the notion of homophily used is based on group identities that are exogenous and immutable. In contrast, we consider a homophily that arises from the desire to be with neighbors who are behaviorally similar, not necessarily those who have the same group identity. The distinction matters because behaviors are neither exogenous nor immutable but choices that can change as individuals adapt to their neighborhoods. We show that in such an environment, integration rather than segregation is the typical outcome. However, the tendency toward adaptation and integration can be impeded when economic frictions in the form of income inequality and housing cost are present.
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Habitação , Características de Residência , Humanos , RendaRESUMO
BACKGROUND: Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). METHODS: A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. RESULTS: The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-ß-mediated activation of Smad2/3 and downstream profibrotic gene expression. CONCLUSIONS: Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.
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Over the past few decades, there have been major developments in transition metal-catalyzed asymmetric cyclization reactions, enabling the convenient access to a wide spectrum of structurally diverse chiral carbo- and hetero-cycles, common skeletons found in fine chemicals, natural products, pharmaceuticals, agrochemicals, and materials. In particular, a plethora of enantioselective cyclization reactions have been promoted by chiral palladium catalysts owing to their outstanding features. This review aims to collect the latest advancements in enantioselective palladium-catalyzed cyclization reactions over the past eleven years, and it is organized into thirteen sections depending on the different types of transformations involved.
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Asymmetric Pd-catalyzed three-component carboamination reactions of dienes to construct chiral cyclohexenylamines, which are of great importance in many fields of chemistry, have remained largely unexplored. Here, we demonstrate a highly enantio- and regioselective Pd/Ming-Phos-catalyzed carboamination reactions of 1,3-cyclohexadiene with readily available aryl iodides and anilines for facile access to diverse valuable chiral cyclohexenylamines. The process shows excellent functional group tolerance, easy scalability, and mild conditions. Moreover, mechanistic studies suggest that this reaction has a first-order dependence on the concentration of the palladium catalyst and aniline.
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Cholesterol-rich membranes play a pivotal role in cancer initiation and progression, necessitating innovative approaches to target these membranes for cancer inhibition. Here we report the first case of unnatural peptide (1) assemblies capable of depleting cholesterol and inhibiting cancer cells. Peptide 1 self-assembles into micelles and is rapidly taken up by cancer cells, especially when combined with an acute cholesterol-depleting agent (MßCD). Click chemistry has confirmed that 1 depletes cell membrane cholesterol. It localizes in membrane-rich organelles, including the endoplasmic reticulum, Golgi apparatus, and lysosomes. Furthermore, 1 potently inhibits malignant cancer cells, working synergistically with cholesterol-lowering agents. Control experiments have confirmed that C-terminal capping and unnatural amino acid residues (i.e., BiP) are essential for both cholesterol depletion and potent cancer cell inhibition. This work highlights unnatural peptide assemblies as a promising platform for targeting the cell membrane in controlling cell fates.
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Colesterol , Peptídeos , Humanos , Colesterol/química , Colesterol/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacosRESUMO
Developing Janus fabrics with excellent one-way sweat transport capacity is an attractive way for providing comfort sensation and protecting the health during exercise. In this work, a 3D wetting gradient Janus fabric (3DWGJF) is first proposed to address the issue of excessive sweat accumulation in women's breasts, followed by integration with a sponge pad to form a 3D wetting gradient Janus sports bra (3DWGJSB). The 3D wetting gradient enables the prepared fabric to control the horizontal migration of sweat in one-way mode (x/y directions) and then unidirectionally penetrate downward (z direction), finally keeping the water content on the inner side of 3DWGJF (skin side) at ≈0%. In addition, the prepared 3DWGJF has good water vapor transmittance rate (WVTR: 0.0409 g cm-2 h-1) and an excellent water evaporation rate (0.4704 g h-1). Due to the high adhesion of transfer prints to the fabrics and their excellent mechanical properties, the 3DWGJF is remarkably durable and capable of withstanding over 500 laundering cycles and 400 abrasion cycles. This work may inspire the design and fabrication of next-generation moisture management fabrics with an effective sweat-removal function for women's health.
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High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.
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Hepacivirus , Hepatite C , Humanos , Hepacivirus/genética , Análise Custo-Benefício , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Fatores de Risco , RNARESUMO
Quantum dot (QD) light-emitting diodes (QLEDs) are promising for next-generation lighting and displays. Considering the optimization design of both the QD and device structure is expected to improve the QLED's performance significantly but has rarely been reported. Here, we use the thick-shell QDs combined with a dual-hole transport layer device structure to construct a high-efficiency QLED. The optimized thick-shell QDs with CdS/CdSe/CdS/ZnS seed/spherical quantum well/shell/shell geometry exhibit a high photoluminescence quantum yield of 96% at a shell thickness of 5.9â nm. The intermediate emissive CdSe layer with coherent strain ensures defect-free growth of the thick CdS and ZnS outer shells. Based on the orthogonal solvents assisted Poly-TPD&PVK dual-hole transport layer device architecture, the champion QLED achieved a maximum external quantum efficiency of 22.5% and a maximum luminance of 259955 cd m-2, which are 1.6 and 3.7 times that of thin-shell QDs based devices with single hole transport layer, respectively. Our study provides a feasible idea for further improving the performance of QLED devices.
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Ultraviolet-based optical wireless communication (OWC) is emerging as a significant technology for the next-generation secure communication, particularly within the solar-blind spectra. In this study, we have synthesized two types of green-emitting II-VI family colloidal quantum dots (QDs), specifically ZnCdSe/ZnS and CdSe/CdZnS/ZnS QDs, which are stimulated by ultraviolet (UV) and solar-blind deep-ultraviolet (DUV) light, respectively. With a transmission distance of 1.5â m, the maximum data rate of ZnCdSe/ZnS QDs reaches 40â Mb/s, which is below the forward-error-correction (FEC) limit (3.8 × 10-3) when excited by 385-nm UV light. However, both brightness and bit error rate are significantly deteriorated when excited by 280-nm DUV light. Conversely, 28 and 24â Mb/s were attained using CdSe/CdZnS/ZnS QDs under UV and DUV excitation, respectively. Our studies on light-conversion and communication capabilities of green QDs within the DUV OWC system may provide valuable insights for subsequent research in the field.
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We demonstrate an optical fiber-based, multiple-access frequency transmission using two optical frequency combs. The experimental results using the Allan deviation analysis show that with the phase compensation technique, the frequency instabilities at the remote site are 8.7 × 10-15/1 s and 1.0 × 10-17/103 s, and at the accessing node along the fiber link, the frequency instabilities are 6.9 × 10-15/1 s and 1.1 × 10-17/103 s. Similarly, the power spectral density of phase noise was analyzed in the frequency domain. These experimental results demonstrate that the compensation scheme improved the performance by two to three orders of magnitude. Thus, the proposed frequency transmission technique has potential application for disseminating ultrastable frequency references in the optical fiber network.
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A high-performance 5-junction cascade quantum dot (QD) vertical cavity surface-emitting laser (VCSEL) with 1.3â µm wavelength was designed. The characteristics of the QD as active regions and tunnel junctions are combined to effectively increase output power. The photoelectric characteristics of single-junction, 3-junction cascade, and 5-junction cascade QD VCSELs are compared at continuous-wave conditions. Results indicate that the threshold current gradually decreases, and the output power and slope efficiency exponential increase with the increase of the number of active regions. The peak power conversion efficiency of 58.4% is achieved for the 5-junction cascade individual QD VCSEL emitter with 10â µm oxide aperture. The maximum slope efficiency of the device is 6.27â W/A, which is approximately six times than that of the single-junction QD VCSEL. The output power of the 5-junction cascade QD VCSEL reaches 188.13â mW at injection current 30â mA. High-performance multi-junction cascade 1.3-µm QD VCSEL provides data and theoretical support for the preparation of epitaxial materials.
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BACKGROUND: Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or increasing brain atrophy, respectively. METHODS: We used bidirectional two-sample Mendelian randomisation to estimate the effects between genetic liability to AD and global and regional cortical thickness, estimated total intracranial volume, volume of subcortical structures and total white matter in 37 680 participants aged 8-81 years across 5 independent cohorts (Adolescent Brain Cognitive Development, Generation R, IMAGEN, Avon Longitudinal Study of Parents and Children and UK Biobank). We also examined the effects of global and regional cortical thickness and subcortical volumes from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium on AD risk in up to 37 741 participants. RESULTS: Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. Some of the identified structures are not typically implicated in AD, such as those in the striatum (eg, thalamus), with consistent effects from childhood to late adulthood. There was little evidence to suggest brain morphology alters AD risk. CONCLUSIONS: Genetic liability to AD is likely to affect risk of AD primarily through mechanisms affecting indicators of brain morphology in later life, rather than structural brain reserve. Future studies with repeated measures are required for a better understanding and certainty of the mechanisms at play.
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Targeting immunosuppressive metastatic cancer cells is a key challenge in therapy. We recently have shown that a rigid-rod aromatic, pBP-NBD, that responds to enzymes and kill immunosuppressive metastatic osteosarcoma (mOS) and castration resistant prostate cancer (CRPC) cells in mimetic bone microenvironment. However, pBP-NBD demonstrated moderate efficacy against CRPC cells. To enhance activity, we incorporated the unnatural amino acid L- or D-4,4'-biphenylalanine (L- or D-BiP) into pBP-NBD, drastically increasing cellular uptake and CRPC inhibition. Specifically, we inserted BiP into pBP-NBD to target mOS (Saos2 and SJSA1) and CRPC (VCaP and PC3) cells with overexpressed phosphatases. Our results show that the D-peptide backbone with an aspartate methyl diester at the C-terminal offers the highest activity against these immunosuppressive mOS and CRPC cells. Importantly, imaging shows that the peptide assemblies almost instantly enter the cells and accumulate primarily within the endoplasmic reticulum of Saos2, SJSA1, and PC3 cells and at the lysosomes of VCaP cells. By using BiP to boost cellular uptake and self-assembly within cancer cells, this work illustrates an unnatural hydrophobic amino acid as a versatile and effective residue to boost endocytosis of synthetic peptides for intracellular self-assembly.
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Aminoácidos , Humanos , Linhagem Celular Tumoral , Aminoácidos/química , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/química , Endocitose/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologiaRESUMO
BACKGROUND: The roles of Lenalidomide (Len) and Daratumumab (Dara) in multiple myeloma treatment are well-established, yet their influences on hematopoietic stem cell harvesting and reconstitution remain disputed. METHODS: We conducted a systematic database review to identify cohort studies or RCTs evaluating the effect of the use of Len or Dara on hematopoietic stem cell collection and peripheral blood count recovery in multiple myeloma patients. Effects on hematopoietic collection or reconstitution were estimated by comparing standardized mean differences (SMD) and mean differences (MD), or median differences. RESULTS: Eighteen relevant studies were identified, summarizing mobilization results. For Len, data from 13 studies were summarized, including total CD34+ cell yield, collection failure rate, and time to neutrophil and platelet engraftment. Results indicated that Len exposure led to decreased stem cell collection [SMD=-0.23, 95% CI (-0.34, -0.12)]. However, collection failure (<2×106) could be mitigated by plerixafor [OR=2.14, 95% CI (0.96, 4.77)]. For Dara, two RCTs and three cohort studies were included, showing that Dara exposure resulted in a reduction in total stem cells even with optimized plerixafor mobilization [SMD=-0.75, 95% CI (-1.26, -0.23)], and delayed platelet engraftment recovery [MD=1.20, 95% CI (0.73, 1.66)]. CONCLUSIONS: Our meta-analysis offers a comprehensive view of Len and Dara's impacts on hematopoietic stem cell collection and reconstitution in multiple myeloma. Len usage could lead to reduced stem cell collection, counteracted by plerixafor mobilization. Dara usage could result in diminished stem cell collection and delayed platelet engraftment.
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Although the formation of peptide assemblies catalyzed by alkaline phosphatase (ALP) has received increasing attention in inhibiting cancer cells, the detailed enzyme kinetics of the dephosphorylation of the corresponding phosphopeptide assemblies have yet to be determined. We recently discovered that assemblies from a phosphopentapeptide can form intracellular nanoribbons that kill induced pluripotent stem cells or osteosarcoma cells, but the kinetics of enzymatic dephosphorylation remain unknown. Thus, we chose to examine the enzyme kinetics of the dephosphorylation of the phosphopentapeptide [NBD-LLLLpY (1)] from concentrations below to above its critical micelle concentration (CMC). Our results show that the phosphopeptide exhibits a CMC of 75 µM in phosphate saline buffer, and the apparent Vmax and Km values of alkaline phosphatase catalyzed dephosphorylation are approximately 0.24 µM/s and 5.67 mM, respectively. Despite dephosphorylation remaining incomplete at 60 min in all the concentrations tested, dephosphorylation of the phosphopeptide at concentrations of 200 µM or above mainly results in nanoribbons, dephosphorylation at concentrations of CMC largely produces nanofibers, and dephosphorylation below the CMC largely generates nanoparticles. Moreover, the formation of nanoribbons correlates with the intranuclear accumulation of the pentapeptide. By providing the first examination of the enzymatic kinetics of phosphopeptide assemblies, this work further supports the notion that the assemblies of phosphopentapeptides can act as a new functional entity for controlling cell fates.
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Nanotubos de Carbono , Fosfopeptídeos , Fosfatase Alcalina/metabolismo , CinéticaRESUMO
The uncontrolled bacterial infection-induced cytokine storm and sequential immunosuppression are commonly observed in septic patients, which indicates that the activation of phagocytic cells and the efficient and timely elimination of bacteria are crucial for combating bacterial infections. However, the role of dysregulated immune cells and their disrupted function in sepsis remains unclear. Here, we found that macrophages exhibited the impaired endocytosis capabilities in sepsis by Single-cell RNA sequencing and bulk RNA sequencing. Caveolae protein Caveolin-1 (Cav-1) of macrophages was inactivated by SHP2 rapidly during Escherichia coli (E.coli) infection. Allosteric inhibitor of SHP2 effectively maintains Cav-1 phosphorylation to enhance macrophage to endocytose and eliminate bacteria. Additionally, TLR4 endocytosis of macrophage was also enhanced upon E.coli infection by SHP099, inducing an increased and rapidly resolved inflammatory response. In vivo, pretreatment or posttreatment with inhibitor of SHP2 significantly reduced the bacterial burden in organs and mortality of mice subjected E.coli infection or CLP-induced sepsis. The cotreatment of inhibitor of SHP2 with an antibiotic conferred complete protection against mortality in mice. Our findings suggest that Cav-1-mediated endocytosis and bacterial elimination may play a critical role in the pathogenesis of sepsis, highlighting inhibitor of SHP2 as a potential therapeutic agent for sepsis.
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Cavéolas , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Sepse , Animais , Humanos , Camundongos , Bactérias , Cavéolas/metabolismo , Endocitose , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/metabolismo , Macrófagos , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Sepse/tratamento farmacológico , Sepse/metabolismoRESUMO
INTRODUCTION: The approval of novel biologic agents and small molecules for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) is dependent on phase 3 randomized controlled trials (RCTs). However, these trials sometimes fail to achieve the expected efficacy outcomes observed in phase 2 trials. METHODS: We conducted a systematic review of RCTs that evaluated biologic agents and small molecules using paired regimens in both phase 2 and phase 3. We searched Medline, EMBASE, and Cochrane databases up until February 13, 2024. The revised Cochrane tool was utilized to assess the risk of bias. A generalized linear mixed-effects model (GLMM) was employed to estimate the odds ratios (ORs) for efficacy outcomes in phase 2 trials compared to phase 3. RESULTS: We identified a total of 23 trials with 10 paired regimens for CD and 30 trials with 11 paired regimens for UC. The GLMM analysis revealed that phase 2 CD trials had higher outcomes measured by the Crohn's Disease Activity Index (CDAI) by 9-13% without statistical significance: CDAI-150: OR, 1.12 (95% CI 0.83-1.51, p = 0.41); CDAI-100: OR, 1.09 (95% CI 0.88-1.35, p = 0.40); or CDAI-70: OR, 1.13 (95% CI 0.61-2.08, p = 0.66). For UC, two efficacy outcomes were estimated to be equally reported in phase 2/phase 3 pairs: clinical remission: OR, 1.00 (95% CI 0.83-1.20, p = 0.96); endoscopic improvement: OR, 0.98 (95% CI 0.83-1.15, p = 0.79). However, the rate of clinical response was underestimated in phase 2 by 19%: OR, 0.81 (95% CI 0.70-0.95, p = 0.03). The inclusion criterion for the type of Mayo score for UC had a significant interaction with the study phase to influence the difference in clinical response (p = 0.002). CONCLUSIONS: Our findings suggest that the main efficacy outcomes for CD and UC remain consistent between phase 2 and phase 3 trials, except for UC response rates. The efficacy data obtained from phase 2 trials can be considered reliable for the design of subsequent phase 3 trials. REGISTRATION: PROSPERO (CRD42023407947).
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Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Colite Ulcerativa , Doença de Crohn , Doença de Crohn/tratamento farmacológico , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/terapia , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , AdultoRESUMO
INTRODUCTION: Endovascular aneurysm repair using iodinated contrast agents risks contrast-induced nephropathy, especially in high-risk patients. This technical note describes a contrast-free endovascular aneurysm repair (EVAR) protocol using preoperative imaging measurement and fibrin sealant (FS) filling. TECHNIQUE: Preoperative imaging measurement and intraoperative guidewire manipulation facilitated anatomical identification without contrast. After endograft deployment, the aneurysm sac was filled with FS if endoleak was indicated by pressure fluctuations. RESULT: Between 2017 and 2020, 6 high-risk patients underwent contrast-free EVAR with FS filling. Complete exclusion was achieved in all cases. Over follow-up, no endoleaks, deterioration in renal function, or other complications were observed. CONCLUSION: Contrast-free EVAR with FS filling shows early feasibility as an alternative technique for contrast-induced nephropathy (CIN) high-risk patients, while larger studies with long-term monitoring are imperative to validate outcomes. CLINICAL IMPACT: This study showcases a contrast-free EVAR technique with fibrin sealant filling for high-risk CIN patients. It offers a safer approach for those with renal challenges, reducing CIN risk. The technique's feasibility in a small cohort suggests its utility in treating AAA without iodinated contrast, crucial for patients with specific health risks. For clinicians, it introduces a method that decreases nephrotoxic risks, potentially changing practice for vulnerable patients.