RESUMEN
Stereotactic needle biopsy stands as a crucial method for diagnosing intracranial lesions unsuitable for surgical intervention. Nonetheless, the potential for sampling errors lead to innovative approaches to enhance diagnostic precision. This study contrasts the outcomes of patients undergoing fluorescein-assisted frameless stereotactic needle biopsy with those receiving traditional biopsies to evaluate the impact on diagnostic accuracy and safety. This study included patients with contrast-enhancing intracranial lesions, comprising a prospective group undergoing fluorescein-assisted biopsies and a retrospective group undergoing conventional biopsies at the same institution. We've collected data on demographics, procedural specifics, diagnostic outcomes, and postoperative events. A comparative analysis involved 43 patients who received fluorescein-assisted biopsies against 77 patients who underwent conventional biopsies. The average age was 60.5 years. The fluorescein group exhibited a 93% success rate in diagnosis, markedly higher than the 70.1% in the non-fluorescein group (OR = 5.67; 95%IC: 1.59-20.24; p < 0.01). The rate of complications was statistically similar across both cohorts. Despite its established value, stereotactic needle biopsy is susceptible to inaccuracies and complications. The application of fluorescence-based adjuncts like 5-ALA and fluorescein has been investigated to improve diagnostic fidelity and reduce risks. These technologies potentially minimize the necessity for multiple biopsies, decrease surgical duration, and provide immediate verification of tumor presence. Fluorescein-assisted stereotactic biopsy emerges as an effective, secure alternative to conventional methods.
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Neoplasias Encefálicas , Fluoresceína , Humanos , Persona de Mediana Edad , Femenino , Masculino , Anciano , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico , Biopsia con Aguja/métodos , Biopsia con Aguja/efectos adversos , Adulto , Estudios Retrospectivos , Técnicas Estereotáxicas , Anciano de 80 o más Años , Estudios ProspectivosRESUMEN
PURPOSE: Brain metastases (BM) often leave residual tumors despite having visible margins, which increases the risk of local tumor recurrence and can impact overall patient survival rates. Fluorescence-guided surgery (FGS) utilizing sodium fluorescein (FL) has been reported as an effective technique in recent studies. This study aimed to evaluate the efficacy of FL FGS in improving the extent of resection of brain metastases and its impact on overall survival. METHODS: We conducted a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Our primary focus was on gross total resection (GTR). Additionally, we extracted survival data and evaluated the risk of bias using a modified version of the Joanna Briggs Institute critical appraisal tool. RESULTS: The study comprised 970 patients with brain metastases through eight different studies. The study found that patients who underwent FL-guided resection had a significantly higher rate of GTR (OR: 2.02, 95% CI: 1.14-3.56, p = 0.0156, I2 = 41.5%). Additionally, the study concluded that FL-guided resection is associated with better overall survival rates (HR: 0.61, 95%CI: 0.47 0.80, p = 0.0003, I2 = 41.5%). CONCLUSION: Our research suggests that the use of FL is associated with a higher rate of GTR and improved overall patient survival. None of the studies we reviewed reported significant complications associated with the use of FL in patients.
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Neoplasias Encefálicas , Fluoresceína , Humanos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/secundario , Cirugía Asistida por Computador/métodos , Procedimientos Neuroquirúrgicos/métodos , Colorantes FluorescentesRESUMEN
Synthetic single-chain bolalipids (SSCBs) are novel excipients in drug delivery, with potential as stabilizers or solubilizers. However, their impact on skin barrier function has not been comprehensively studied. Therefore, two SSCBs (PC-C24-PC and PC-C32-PC) were studied in aqueous systems for their impact on penetration of a model permeant into porcine skin. Concentrations of 0.05 - 5 % w/w were tested; PC-C24-PC formulations were low-viscosity liquids while PC-C32-PC formed viscous dispersions to gels at room temperature. Formulations were compared for their ability to enhance sodium fluorescein penetration (SF, 0.1 % w/w) into skin via tape stripping. Using NIR-densitometry, the effect of SSCB formulations on corneocyte cohesion was evaluated. Data were compared with phospholipid mixture Lipoid S-75, sodium dodecyl sulfate (SDS), and polyethylene glycol 12-hydroxystearate (PEG-HS), and distilled water as negative control. Contrary to the hypothesis, both SSCBs failed to increase SF penetration into the stratum corneum, but rather showed a significant decrease in penetration depth compared to water. Both SSCBs exhibited a keratolytic effect at 5 % w/w, leading to substantial removal of proteins from the skin surface. Consequently, SSCBs may not enhance penetration of hydrophilic drugs into skin, but could be used as keratolytic agents.
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Excipientes , Interacciones Hidrofóbicas e Hidrofílicas , Absorción Cutánea , Piel , Porcinos , Animales , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Piel/efectos de los fármacos , Excipientes/química , Sistemas de Liberación de Medicamentos/métodos , Administración Cutánea , Fluoresceína , Viscosidad , Química Farmacéutica/métodos , PermeabilidadRESUMEN
MoO3-x NPs was rapidly synthesized at room temperature by an easy stirring method. It was interesting to find that MoO3-x NPs induce OH- to generate active free radicals (ROS), which is a highly promising property in chemiluminescence (CL). Benefiting from the abundant oxygen vacancy, MoO3-x NPs adsorbs H2O2 and turn it into ·OH. The oxidase activity of fluorescein under visible light had already been reported, which catalyzes dissolved oxygen to become O2-· and continue to convert to H2O2. By creating the synergy effect with fluorescein, MoO3-x NPs strengthen the CL intensity of K3[Fe(CN)6]-fluorescein system significantly. Utilizing the quench effect of uric acid for the CL intensity, we developed a rapid, simple, and highly sensitive CL platform for uric acid detection. The linear range was 5-80 µM and the detection limit (LOD) for uric acid was 3.11 µM (S/N = 3). This work expanded the application of MoO3-x NPs in the CL field and developed a simple and highly sensitive CL sensing system to detect UA in human saliva.
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Fluoresceína , Límite de Detección , Molibdeno , Óxidos , Saliva , Ácido Úrico , Ácido Úrico/análisis , Ácido Úrico/química , Saliva/química , Humanos , Fluoresceína/química , Óxidos/química , Molibdeno/química , Mediciones Luminiscentes/métodos , Peróxido de Hidrógeno/químicaRESUMEN
OBJECTIVE: Indocyanine green (ICG) and sodium fluorescein (Na-Fl) are two fluorophores, which are used for videoangiography purposes. This prospective study reports our experience by using surgical microscopes equipped with two special filters. We compared the imaging efficacy of Na-FL and ICG videoangiography techniques during aneurysm and arteriovenous malformations (AVM) surgeries. PATIENT AND METHODS: Fourtynine consecutive patients were operated between September 2015 and December 2022. Patients with ruptured/unruptured aneurysms or with AVMs presented with/without hemorrhage were included to the current study. RESULTS: There were a total of 48 aneurysms and 11 AVMs in 49 patients in the current study. Na-Fl enables the surgeon to manipulate vessels and aneurysms real-time. ICG provides the ability to watch the videoangiography repeatedly and understand the angioarchitecture. The use of FLOW-800 module allows the surgeon to make concrete judgements about the flow dynamics of AVMs and therefore ICG videoangiography found useful in AVM surgery. Na-Fl has been found more useful for the evalution of the low caliber perforating arteries and anatomical features of the aneursym dome in aneurysm surgery. CONCLUSION: The results of our series demonstrated the safety and efficacy of Na-Fl use in the surgery of aneurysms and AVMs. Both the ICG and Na-Fl videoangiographies are easy to perform and complimentary to each other. Combined use of these two mediums may provide better surgical results, considering the separate advantages and disadvantages of these both techniques.
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Angiografía Cerebral , Fluoresceína , Verde de Indocianina , Aneurisma Intracraneal , Malformaciones Arteriovenosas Intracraneales , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Adulto , Malformaciones Arteriovenosas Intracraneales/cirugía , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Angiografía Cerebral/métodos , Anciano , Procedimientos Neuroquirúrgicos/métodos , Estudios Prospectivos , Colorantes , Adulto Joven , Monitoreo Intraoperatorio/métodosRESUMEN
PURPOSE: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs. METHODS: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity. RESULTS: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions. CONCLUSION: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs.
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Neoplasias Encefálicas , Fluoresceína , Humanos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Procedimientos Neuroquirúrgicos/métodos , Cirugía Asistida por Computador/métodos , Luz/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare the ocular surface disease index (OSDI) questionnaire with objective tests in dry eye disease. STUDY DESIGN: A prospective observational study. Place and Duration of the Study: Department of Ophthalmology, Nigde Omer Halisdemir University, Nigde, Turkiye, from 9th June to 31st December 2022. METHODOLOGY: All clinically diagnosed 323 eyes of patients with dry eye disease (DED) were included. The subjects were evaluated by the Oxford classification of corneal and conjunctival fluorescein staining, Schirmer I test, and fluorescein tear breakup time (TBUT). Symptoms of the patients were interpreted with OSDI and correlations of symptoms and objective markers were analysed. RESULTS: There was no significant association between any objective signs (Schirmer I, TBUT, and Oxford), and OSDI (p = 0.26, 0.52, 0.18, and respectively). Schirmer I score showed a significant positive correlation with TBUT (p <0.001, r = 0.21) and a significant negative correlation with Oxford scale (p <0.001, r = -0.19). There was a statistically negative correlation between TBUT and Oxford scale (p <0.001, r = -0.37). CONCLUSION: Except for the Schirmer test, TBUT and Oxford scale are effective tools in the diagnosis of DED. Symptom markers, such as OSDI may have lower reliability in diagnosing DED and determining its severity. Diagnostic tests are important in the detection of asymptomatic or less severe dry eye disease that can be ignored. KEY WORDS: Dry eye disease, Diagnosis, Ocular surface disease index (OSDI), Tear breakup time (TBUT), Oxford grading scale, Schirmer I test.
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Síndromes de Ojo Seco , Lágrimas , Humanos , Síndromes de Ojo Seco/diagnóstico , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Anciano , Fluoresceína , Índice de Severidad de la EnfermedadRESUMEN
Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated Protein (CRISPR-Cas) systems have evolved several mechanisms to specifically target foreign DNA. These properties have made them attractive as biosensors. The primary drawback associated with contemporary CRISPR-Cas biosensors is their weak signaling capacity, which is typically compensated for by coupling the CRISPR-Cas systems to nucleic acid amplification. An alternative strategy to improve signaling capacity is to engineer the reporter, i.e., design new signal-generating substrates for Cas proteins. Unfortunately, due to their reliance on custom synthesis, most of these engineered reporter substrates are inaccessible to many researchers. Herein, we investigate a substrate based on a fluorescein (FAM)-tetramethylrhodamine (TAMRA) Förster resonant energy-transfer (FRET) pair that functions as a seamless "drop-in" replacement for existing reporters, without the need to change any other aspect of a CRISPR-Cas12a-based assay. The reporter is readily available and employs FRET to produce two signals upon cleavage by Cas12a. The use of both signals in a ratiometric manner provides for improved assay performance and a decreased time-to-result for several CRISPR-Cas12a assays when compared to a traditional FAM-Black Hole Quencher (BHQ) quench-based reporter. We comprehensively characterize this reporter to better understand the reasons for the improved signaling capacity and benchmark it against the current standard CRISPR-Cas reporter. Finally, to showcase the real-world utility of the reporter, we employ it in a Recombinase Polymerase Amplification (RPA)-CRISPR-Cas12a DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR) assay to detect Human papillomavirus in patient-derived samples.
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Sistemas CRISPR-Cas , Transferencia Resonante de Energía de Fluorescencia , Rodaminas , Transferencia Resonante de Energía de Fluorescencia/métodos , Sistemas CRISPR-Cas/genética , Humanos , Rodaminas/química , Técnicas Biosensibles/métodos , Límite de Detección , Fluoresceína/química , Proteínas Asociadas a CRISPR/genética , Colorantes Fluorescentes/química , Proteínas Bacterianas/genética , EndodesoxirribonucleasasRESUMEN
Type 2 Diabetes Mellitus (T2DM) is linked to multiple complications, including cognitive impairment, and the prevalence of memory-related neurodegenerative diseases is higher in T2DM patients. One possible theory is the alteration of the microvascular and macrovascular environment of the blood-brain barrier (BBB). In this study, we employed different approaches, including RT-PCR, functional pharmacokinetic studies using sodium fluorescein (NaFL), and confocal microscopy, to characterize the functional and molecular integrity of the BBB in a T2DM animal model, leptin receptor-deficient mutant mice (Leprdb/db mice). As a result, VCAM-1, ICAM-1, MMP-9, and S100b (BBB-related markers) dysregulation was observed in the Leprdb/db animal model compared to littermate wild-type mice. The brain concentration of sodium fluorescein (NaFL) increased significantly in Leprdb/db untreated mice compared to insulin-treated mice. Therefore, the permeability of NaFL was higher in Leprdb/db control mice than in all remaining groups. Identifying the factors that increase the BBB in Leprdb/db mice will provide a better understanding of the BBB microvasculature and present previously undescribed findings of T2DM-related brain illnesses, filling knowledge gaps in this emerging field of research.
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Barrera Hematoencefálica , Diabetes Mellitus Tipo 2 , Modelos Animales de Enfermedad , Receptores de Leptina , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Ratones , Receptores de Leptina/metabolismo , Receptores de Leptina/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Fluoresceína/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Subunidad beta de la Proteína de Unión al Calcio S100/metabolismo , Subunidad beta de la Proteína de Unión al Calcio S100/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Masculino , Diabetes Mellitus Experimental/metabolismo , Permeabilidad , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: The use of fluorescent technologies in vascular neurosurgery emerged after indocyanine green video angiography (ICG-VA) was first described in 2003. As data supporting the efficiency of ICG in preventing postoperative complications has grown substantially, it has now established itself as the standard of care. However, the predominant literature centers on ICG techniques, leaving the evaluation of cost-effective fluorescein tools pending. We report the results of a prospective study in which we demonstrated the impact of intraoperative fluorescein videoangiography (FL-VA) in aneurysm surgery. METHODS: Between December 2021 and September 2022, a total of 57 patients underwent craniotomy for intracranial aneurysm surgery. After aneurysm clipping, we administered a 0.5 mg/Kg of sodium fluorescein, and the intracranial area of interest was inspected through the microscope integrated module. The following data were collected: patient age and sex; number of clipped aneurysms; aneurysm location, size, and rupture status; Hunt Hess grade; intraoperative rupture; aneurysm calcification and thrombosed aneurysm; visualization of blood flow in perforating arteries; need for a clip adjustment after FL-VA analysis by neurosurgeon. RESULTS: For the surgical clipping of 64 aneurysms in 57 patients, 80 FL-VA studies were performed. Clip adjustments were performed following FL-VA in 13 aneurysms. FL-VA had an impact on 20 % of the clipping. In seven aneurysms, clip adjustment was due to the "presence of residual aneurysm", in three cases due to the "presence of neck", and in three cases due to "adjacent vessel stenosis". Regarding the evaluation of flow in the perforating vessels, it was possible, with a good and detailed image in all cases. CONCLUSION: The use of FL-VA has a significant impact in aneurysm surgery, enhancing effectiveness and safety. The dosage of 0.5 mg/kg administered is sufficient for assessing both aneurysm occlusion and the presence of flow in adjacent vessels.
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Angiografía Cerebral , Fluoresceína , Aneurisma Intracraneal , Procedimientos Neuroquirúrgicos , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Adulto , Angiografía Cerebral/métodos , Procedimientos Neuroquirúrgicos/métodos , Craneotomía/métodos , Angiografía con Fluoresceína/métodosRESUMEN
Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multidrug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a six-parameter version of this model to control time-course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, found the mean estimated value for each parameter, and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.NEW & NOTEWORTHY We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile.
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Fluoresceína , Hígado , Modelos Biológicos , Daño por Reperfusión , Daño por Reperfusión/metabolismo , Hígado/metabolismo , Animales , Fluoresceína/farmacocinética , Fluoresceína/metabolismo , Perfusión , Isquemia Tibia , Bilis/metabolismo , Trasplante de Hígado , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Preservación de Órganos/métodos , Eliminación Hepatobiliar , Transportadoras de Casetes de Unión a ATPRESUMEN
To establish the correlation between thermal conditions imposed on bloodstains and visualizing effect of enhancement techniques, infrared photography and four chemical enhancement reagents were used to visualize bloodstains following thermal exposure. A black tile was selected as the substrate to intensify the visualization challenge, with a Cone Calorimeter serving as the standardized heating source to control thermal conditions. Compared with standard photography, infrared photography is proven to be a valuable complement to chemical reagents, showing significant advantages in visualizing bloodstains after thermal exposure. However, it is worth noting that infrared image fell short of standard image when bloodstains displayed raised, embossed morphology or when bloodstains almost disappeared under specific conditions. The enhancement effectiveness was found to be strongly correlated with thermal conditions imposed on bloodstains, and the morphology evolution of bloodstains during heating affected the chemical enhancement effect additionally, especially when the bulge morphology was formed, and it was observed that reagents were more effective after removing the dense shell of the bulge. Among the four selected chemical enhancement reagents, fluorescein performed exceptionally well, maintaining its effectiveness even for bloodstains heated at 641°C for 10 min. TMB demonstrated its visualizing ability for bloodstains heated at 396°C for 5 min and heated at 310°C for 20 min. BLUESTAR® followed afterwards, while luminol performed worst. The correlation between thermal conditions imposed on bloodstains and the corresponding visualizing effectiveness of enhancement techniques provides important references for detecting bloodstains at fire scenes.
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Manchas de Sangre , Calor , Fotograbar , Humanos , Rayos Infrarrojos , Luminol , Fluoresceína , Indicadores y Reactivos , Calorimetría , Colorantes Fluorescentes , Medicina Legal/métodos , Sustancias LuminiscentesRESUMEN
Controlled release of low molecular weight hydrophilic drugs, administered locally, allows maintenance of high concentrations at the target site, reduces systemic side effects, and improves patient compliance. Injectable hydrogels are commonly used as a vehicle. However, slow release of low molecular weight hydrophilic drugs is very difficult to achieve, mainly due to a rapid diffusion of the drug out of the drug delivery system. Here we present an injectable and self-healing hydrogel based entirely on the self-assembly of liposomes. Gelation of liposomes, without damaging their structural integrity, was induced by modifying the cholesterol content and surface charge. The small hydrophilic molecule, sodium fluorescein, was loaded either within the extra-liposomal space or encapsulated into the aqueous cores of the liposomes. This encapsulation strategy enabled the achievement of controlled and adjustable release profiles, dependent on the mechanical strength of the gel. The hydrogel had a high mechanical strength, minimal swelling, and slow degradation. The liposome-based hydrogel had prolonged mechanical stability in vivo with benign tissue reaction. This work presents a new class of injectable hydrogel that holds promise as a versatile drug delivery system. STATEMENT OF SIGNIFICANCE: The porous nature of hydrogels poses a challenge for delivering small hydrophilic drug, often resulting in initial burst release and shorten duration of release. This issue is particularly pronounced with physically crosslinked hydrogels, since their matrix can swell and dissipate rapidly, but even in cases where the polymers in the hydrogel are covalently cross-linked, small molecules can be rapidly released through its porous mesh. Here we present an injectable self-healing hydrogel based entirely on the self-assembly of liposomes. Small hydrophilic molecules were entrapped inside the extra-liposomal space or loaded into the aqueous cores of the liposomes, allowing controlled and tunable release profiles.
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Preparaciones de Acción Retardada , Hidrogeles , Interacciones Hidrofóbicas e Hidrofílicas , Liposomas , Liposomas/química , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Hidrogeles/química , Inyecciones , Animales , Fluoresceína/químicaRESUMEN
Oral ingestion of fluorescein can be done in ambulatory pediatric clinics. We show that oral ultra-widefield fluorescein angiography is a non-invasive approach to rapidly diagnose and manage a diverse set of pediatric retinal vascular diseases.
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Angiografía con Fluoresceína , Fluoresceína , Fondo de Ojo , Enfermedades de la Retina , Humanos , Angiografía con Fluoresceína/métodos , Niño , Enfermedades de la Retina/diagnóstico , Fluoresceína/administración & dosificación , Masculino , Femenino , Adolescente , Vasos Retinianos/diagnóstico por imagen , Preescolar , Instituciones de Atención Ambulatoria , Administración OralRESUMEN
Background/aim: Awake craniotomy (AC) maximizes the resection of lesions in eloquent brain areas while preserving functionality. Tumor delineation with intraoperative use of sodium fluorescein (NaFl) facilitates total resection. When used with AC, it may allow for safe resection without increasing the risk of postoperative neurologic deficits. This study investigated the efficacy and safety of the combined use of NaFl and AC for maximum safe resection in patients with brain metastases. Material and methods: Patients who underwent AC due to brain metastasis in the Department of Neurosurgery of Uludag University's Faculty of Medicine between January 1, 2018 and August 1, 2022, were retrospectively analyzed. The study comprised 2 patient groups: plain AC (pAC) and NaFl-guided AC (NaFlg-AC). Surgical outcomes related to fluorescence intensity, degree of resection, perioperative complications, and postoperative neurological factors were evaluated. Results: The pAC group included 16 patients (12 males, 4 females), and the NaFlg-AC group comprised 21 (13 males, 7 females). The mean patient ages for males and females were 61.4 years (61.4 ± 9.5 years) and 60.4 years (60.6 ± 12 years), respectively. The most common origin of the metastatic lesion was the lung in both the pAC and NaFlg-AC groups (n = 12 vs. n = 14, respectively). Gross total resection (GTR) was achieved in 85.7% of the patients in the NaFlg-AC group, whereas the GTR rate was 68.7% in the pAC group. There was no significant difference in GTR rates between the 2 groups (p = 0.254). The mean duration of the resection time was significantly shorter in the NaFlg-AC group (45.95 ± 7.00 min vs. 57.5 ± 12.51 min; p = 0.002). The patients' Karnofsky Performance Status (KPS) score did not reach statistical significance at 6-month follow-up in either group compared to their preoperative baseline scores (p = 0.374). KPS did not show a significant difference between the 2 groups at any time. Conclusion: Fluorescence-guided resection in AC for metastatic tumors in sensory, motor, and cognitive areas is a feasible, safe, and convenient technique that significantly increases GTR rates and shortens operative time compared to conventional white light surgery without fluorescence guidance. It also does not increase the incidence of postoperative complications. With the combined use of AC and NaFl, ensuring clear and visible tumor margins during surgery and controlling patients' neurological function in real-time are possible.
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Neoplasias Encefálicas , Craneotomía , Fluoresceína , Humanos , Femenino , Masculino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/secundario , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Craneotomía/métodos , Vigilia , Colorantes FluorescentesRESUMEN
PURPOSE: The vital function of eloquent and deep brain areas necessitates precise treatment for tumors located in these regions. Fluorescein-guided surgery (FGS) has been widely used for high-grade gliomas (HGGs) resection. Nevertheless, the safety and efficacy of utilizing this technique for resecting brain tumors located in eloquent and deep-seated areas remain uncertain. This study aims to assess the safety and extent of resection of HGGs in these challenging tumors with fluorescein and explore its impact on patient survival. METHODS: A retrospective analysis was conducted on the clinical and radiological data of 67 consecutive patients with eloquent or deep-seated HGGs who underwent surgery between January 2020 and June 2023. Lacroix functional location grade was used to determine the eloquence of the tumors. The comparison between the fluorescence-guided surgery group (FGS, n = 32) and the conventional white-light microscopic surgery group (non-FGS, n = 35) included assessments of extent of resection (EOR), rates of gross total resection (GTR, 100%) and near-total resection (NTR, 99 to 98%), postoperative Neurologic Assessment in Neuro-Oncology (NANO) scores, overall survival (OS), and progression-free survival (PFS), to evaluate the safety and efficacy of fluorescein-guided technology in tumor resection at these specific locations. RESULTS: Baseline of demographics, lesion location, and pathology showed no significant difference between the two groups. GTR of the FGS group was higher than the non-FGS group (84.4% vs. 60.0%, OR 3.60, 95% CI 1.18-10.28, p < 0.05). The FGS group also showed higher GTR + NTR (EOR ≥ 98%) than the non-FGS group (93.8% vs. 65.7%, OR 7.83, 95% CI 1.86-36.85, p < 0.01). 87.0% of eloquent tumors (Lacroix grade III) in the FGS group achieved GTR + NTR, compared to 52.2% of control group (OR 6.11, 95% CI 1.50-22.78, p < 0.05). For deep-seated tumors, the rate of GTR + NTR in the two groups were 91.7% and 53.3%, respectively (OR 9.62, 95% CI 1.05-116.50, p < 0.05). No significant difference of the preoperative NANO score of the two groups was found. The postoperative NANO score of the FGS group was significantly lower than the non-FGS group (2.56 ± 1.29 vs. 3.43 ± 1.63, p < 0.05). Median OS of the FGS group was 4.2 months longer than the non-FGS group despite no statistical difference (18.2 months vs. 14.0 months, HR 0.63, 95% CI 0.36-1.11, p = 0.112), while PSF was found significantly longer in FGS patients than those of the non-FGS group (11.2 months vs. 7.7 months, HR 0.59, 95% CI 0.35-0.99, p < 0.05). CONCLUSION: Sodium fluorescein-guided surgery for high-grade gliomas in eloquent and deep-seated brain regions enables more extensive resection while preserving neurologic function and improve patient survival.
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Neoplasias Encefálicas , Fluoresceína , Glioma , Humanos , Femenino , Masculino , Glioma/cirugía , Glioma/patología , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Adulto , Anciano , Cirugía Asistida por Computador/métodos , Procedimientos Neuroquirúrgicos/métodos , Adulto Joven , Clasificación del TumorRESUMEN
The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.
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Antibacterianos , Pseudomonas aeruginosa , Sideróforos , Sideróforos/química , Sideróforos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/metabolismo , Bacterias Gramnegativas/efectos de los fármacos , Colorantes Fluorescentes/química , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Piridonas/farmacología , Piridonas/química , Piridinas/química , Piridinas/farmacología , Animales , Fluoresceína/química , Transporte Biológico , Pruebas de Sensibilidad MicrobianaRESUMEN
Analysis of exosomes provides important information for rapid and non-invasive screening of tumors. However, sensitive and convenient detection of exosomes remains technically challenging to date. Herein, a colorimetric aptasensor based on the light-stimulated oxidase-mimicking activity of FITC was constructed for detecting ovarian cancer (OC) exosomes. The aptasensor contained an EpCAM aptamer to capture OC exosomes. Cholesterol and fluorescein (FITC) were used to modify either end of the DNA (DNA anchor). The DNA anchor could combine with exosomes through a hydrophobic reaction between cholesterol and the lipid membrane. FITC oxidized 3,3',5,5'-tetramethylbenzidine (TMB) under a 365 nm LED light source in a temporally controllable manner under mild conditions, causing the solution to change from colorless to blue, and the corresponding UV-vis absorbance increased. Based on this principle, the exosomes were qualitatively analyzed by observing the color change with the naked eye. In parallel, the exosome concentration was also detected using UV-vis spectrophotometry. The linear range was from 2 × 105 to 100 × 105 particles per mL with a limit of detection of 1.77 × 105 particles per mL. The developed aptasensor also exhibited favorable selectivity and could discriminate the exosomes from OC cells and normal cells. Besides, the receiver operating characteristic (ROC) curve demonstrates that it is possible to distinguish between patients with OC and healthy donors (HDs) using exosomes as the biomarker. Our technology may expand the applications of DNA-based detection method-enabled OC diagnostic tools.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Colorimetría , Exosomas , Exosomas/química , Exosomas/metabolismo , Humanos , Colorimetría/métodos , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Femenino , Neoplasias Ováricas , Oxidorreductasas/química , Oxidorreductasas/metabolismo , Luz , Límite de Detección , Fluoresceína/química , Bencidinas/química , Línea Celular TumoralRESUMEN
PURPOSE: The intraoperative detection of cerebrospinal fluid (CSF) leaks during endoscopic skull base surgery is critical to ensure watertight sealed defects. Intrathecal fluorescein (ITF) is a valuable adjunct to intraoperative investigation. Hence, our aim is to summarize the evidence of the efficacy of ITF as an accurate diagnostic modality and reconstruction guide for non-congenital skull base defects. METHODS: Using the Cochrane Central, MEDLINE, and Embase databases, we identified studies involving the use of ITF in non-congenital CSF leaks which were published until November 2023. The STATA 18 software was used for meta-analysis. RESULTS: Fourteen studies met the inclusion criteria, in which seven studies were included in the meta-analysis. ITF was used in 1898 (90.3%) of patients, with a detection rate of 88.1%. The overall detection rate of non-congenital CSF leaks among ITF concentrations of 5% and 10% had a statistically significant pooled effect size of 2.6 (95% CI = 2.25, 2.95), while when comparing the ITF to other alternative radiological tests, it was not statistically significant with a mean difference of 0.88 (95% CI = - 0.4, 2.16). Moreover, the pooled prevalence was statistically significant in regards of the complications associated with ITF with an effect size of 0.6 (95% CI = 0.39, 0.82), indicating that 60% of patients who underwent ITF would experience at least one of the measured complications. CONCLUSION: ITF is considered as an efficient tool in localizing skull base defects. However, there was no significant results when comparing the ITF to other alternative radiological tests. Accordingly, if the ITF intervention is indicated, patients should be carefully selected based on their clinical need.
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Pérdida de Líquido Cefalorraquídeo , Fluoresceína , Inyecciones Espinales , Base del Cráneo , Humanos , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/anomalías , Base del Cráneo/cirugía , Pérdida de Líquido Cefalorraquídeo/etiología , Colorantes Fluorescentes/administración & dosificación , Endoscopía/métodosRESUMEN
BACKGROUND: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer. OBJECTIVES: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy. METHODS: Eligibility criteria: Studies where SLNB was performed using FS. INFORMATION SOURCES: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool. SYNTHESIS OF RESULTS: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model. RESULTS: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07). CONCLUSION: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis.