Hybrid resection versus conventional resection for laterally spreading lesions of the papilla.

BACKGROUND AND AIMS: Although conventional hot snare resection (CR) of laterally spreading lesions of the major papilla (LSL-Ps) is effective, it can be associated with delayed bleeding in upward of 25% of cases. Given the excellent safety profile of cold snare polypectomy in the colorectum, we investigated the efficacy and safety of a novel hybrid resection (HR) technique for LSL-P management, consisting of hot snare papillectomy plus cold snare resection of the laterally spreading component. METHODS: A prospective cohort of patients underwent HR in a tertiary referral center over 60 months until December 2022. This cohort was compared with a historical cohort of patients who underwent CR at the same institution over 120 months until August 2017. The primary outcomes were recurrence and bleeding. RESULTS: Twenty patients underwent HR (14 female; mean age 65.2 ± 12.2 years). Median lesion size was 30 mm (interquartile range, 25.0-47.5 mm). Recurrent or residual adenoma (RRA) was greater with HR (58.8% [n = 10] vs 29.8% [n = 14]; P = .034). The odds ratio for recurrence was 3.6 times (95% CI, 1.2-11.0) higher with HR (P = .027). RRA was multifocal in 4 (40%) and had a composite RRA volume >10 mm in 7 (70%). The median number of procedures required to treat RRA was higher with HR (4 vs 1, P = .002). There was no difference between CR and HR for intraprocedural bleeding (41.1% [n = 23] vs 25% [n = 5]; P = .587) or delayed bleeding (25.0% vs 10.0%, P = .211). There were no perforations. CONCLUSIONS: The novel HR technique for LSL-P management is associated with a high rate of RRA that is recalcitrant to treatment, without mitigating the risk of intraprocedural or delayed bleeding. Therefore, CR should remain the mainstay management option for treating patients with an LSL-P. (Clinical trial registration number: NCT02306603.).

A Sub-epithelial Lesion Algorithm For Endoscopic (SAFE) Resection In The Upper Gastrointestinal Tract.

INTRODUCTION: Complete excision of upper gastrointestinal sub-epithelial lesions (U-SELs) eliminates diagnostic uncertainty, obviates the need for surveillance and may be necessary for definitive diagnosis and management. Current guidelines lack precision and cohesion, and surgery is associated with significant morbidity. Herein, we describe and report on the outcomes of our SEL algorithm for endoscopic (SAFE) resection. METHODS: U-SELs were enrolled prospectively over 115 months until March 2023. All underwent axial (CT) imaging and endoscopic-ultrasonography (EUS) to exclude a large exophytic component or invasion into local structures, and assess for muscularis propria involvement. RESULTS: 106 U-SELs were resected (mean age 60.6±13.4, 51.9% male; 41 oesophageal, 65 gastric). Oesophageal U-SELs underwent ESD (n=22) or STER if MP involvement was suspected (n=19). Gastric U-SELs underwent STER (n=6 at cardia), ESD (n=47) or exposing-EFTR (n=12). Technical success was 97.6% and 92.3% respectively. Five (7.7%) were completed laparoscopically due to deep and broad full-thickness involvement. Five (7.7%) required laparoscopic gastrotomy and surgical retrieval after successful resection and closure due to a large lesion size (mean 47 mm). There was no delayed bleeding, perforation or recurrence at 13 months. CONCLUSION: U-SELs may be effectively and safely treated by endoscopic resection. The SAFE approach provides a framework that facilitates structured decision-making. Oesophageal U-SELs suspected to involve the MP should undergo STER. Gastric SELs can be best managed by ESD with a view to proceed to exposing-EFTR. A laparoscopic UGI surgeon should be available in case surgical retrieval of the specimen or laparoscopic completion is required.

When less is more: lower esophageal sphincter-preserving peroral endoscopic myotomy is effective for non-achalasia esophageal motility disorders.

BACKGROUND: Non-achalasia esophageal motility disorders (NAEMDs), encompassing distal esophageal spasm (DES) and hypercontractile esophagus (HCE), are rare conditions. Peroral endoscopic myotomy (POEM) is a promising treatment option. In NAEMDs, unlike with achalasia, the lower esophageal sphincter (LES) functions normally, suggesting the potential of LES preservation during POEM. METHODS: This retrospective two-center observational study focused on patients undergoing LES-preserving POEM (LES-POEM) for NAEMD. Eckardt scores were assessed pre-POEM and at 6, 12, and 24 months post-POEM, with follow-up endoscopy at 6 months to evaluate for reflux esophagitis. Clinical success, defined as an Eckardt score ≤3, served as the primary outcome. RESULTS: 227 patients were recruited over 84 months until May 2021. Of these, 16 underwent LES-POEM for an NAEMD (9 with HCE and 7 with DES). The median pre-POEM Eckardt score was 6.0 (interquartile range [IQR] 5.0-7.0), which decreased to 1.0 (IQR 0.0-1.8; P<0.001) 6 months post-POEM. This was sustained at 24 months, with an Eckardt score of 1.0 (IQR 0.0-1.8; P<0.001). Two patients (12.5%) developed Los Angeles grade A or B esophagitis. CONCLUSIONS: LES-POEM for NAEMD demonstrates favorable clinical outcomes, with infrequent esophagitis and reintervention for LES dysfunction rarely required.

A simplified algorithm to evaluate the risk of submucosal invasive cancer in large (≥20 mm) nonpedunculated colonic polyps.

BACKGROUND: Recognition of submucosal invasive cancer (SMIC) in large (≥20 mm) nonpedunculated colonic polyps (LNPCPs) informs selection of the optimal resection strategy. LNPCP location, morphology, and size influence the risk of SMIC; however, currently no meaningful application of this information has simplified the process to make it accessible and broadly applicable. We developed a decision-making algorithm to simplify the identification of LNPCP subtypes with increased risk of potential SMIC. METHODS: Patients referred for LNPCP resection from September 2008 to November 2022 were enrolled. LNPCPs with SMIC were identified from endoscopic resection specimens, lesion biopsies, or surgical outcomes. Decision tree analysis of lesion characteristics identified in multivariable analysis was used to create a hierarchical classification of SMIC prevalence. RESULTS: 2451 LNPCPs were analyzed: 1289 (52.6%) were flat, 1043 (42.6%) nodular, and 118 (4.8%) depressed. SMIC was confirmed in 273 of the LNPCPs (11.1%). It was associated with depressed and nodular vs. flat morphology (odds ratios [ORs] 35.7 [95%CI 22.6-56.5] and 3.5 [95%CI 2.6-4.9], respectively; P<0.001); rectosigmoid vs. proximal location (OR 3.2 [95%CI 2.5-4.1]; P<0.001); nongranular vs. granular appearance (OR 2.4 [95%CI 1.9-3.1]; P<0.001); and size (OR 1.12 per 10-mm increase [95%CI 1.05-1.19]; P<0.001). Decision tree analysis targeting SMIC identified eight terminal nodes: SMIC prevalence was 62% in depressed LNPCPs, 19% in nodular rectosigmoid LNPCPs, and 20% in nodular proximal colon nongranular LNPCPs. CONCLUSIONS: This decision-making algorithm simplifies identification of LNPCPs with an increased risk of potential SMIC. When combined with surface optical evaluation, it facilitates accurate lesion characterization and resection choices.

The Surface Morphology of Large Nonpedunculated Colonic Polyps Predicts Synchronous Large Lesions.

BACKGROUND & AIMS: Large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) may have synchronous LNPCPs in up to 18% of cases. The nature of this relationship has not been investigated. We aimed to examine the relationship between individual LNPCP characteristics and synchronous colonic LNPCPs. METHODS: Consecutive patients referred for resection of LNPCPs over 130 months until March 2022 were enrolled. Serrated lesions and mixed granularity LNPCPs were excluded from analysis. Patients with multiple LNPCPs resected were identified, and the largest was labelled as dominant. The primary outcome was the identification of individual lesion characteristics associated with the presence of synchronous LNPCPs. RESULTS: There were 3149 of 3381 patients (93.1%) who had a single LNPCP. In 232 (6.9%) a synchronous lesion was detected. Solitary lesions had a median size of 35 mm with a predominant Paris 0-IIa morphology (42.9%) and right colon location (59.5%). In patients with ≥2 LNPCPs, the dominant lesion had a median size of 40 mm, Paris 0-IIa (47.6%) morphology, and right colon location (65.9%). In this group, 35.8% of dominant LNPCPs were non-granular compared with 18.7% in the solitary LNPCP cohort. Non-granular (NG)-LNPCPs were more likely to demonstrate synchronous disease, with left colon NG-LNPCPs demonstrating greater risk (odds ratio, 4.78; 95% confidence interval, 2.95-7.73) than right colon NG-LNPCPs (odds ratio, 1.99; 95% confidence interval, 1.39-2.86). CONCLUSIONS: We found that 6.9% of LNPCPs have synchronous disease, with NG-LNPCPs demonstrating a greater than 4-fold increased risk. With post-colonoscopy interval cancers exceeding 5%, endoscopists must be cognizant of an individual's LNPCP phenotype when examining the colon at both index procedure and surveillance. CLINICALTRIALS: gov, NCT01368289; NCT02000141; NCT02198729.

Glutathione-capped gold nanoclusters as near-infrared-emitting efficient contrast agents for confocal fluorescence imaging of tissue-mimicking phantoms.

An innovative research has been conducted focused on demonstrating the ability of novel dual-emissive glutathione-stabilized gold nanoclusters (GSH-AuNCs) to perform bright near-infrared (NIR)-emitting contrast agents inside tissue-mimicking agarose-phantoms via two complementary confocal fluorescence imaging techniques. First, using a new and fast microwave-assisted approach, we synthesized photostable dual-emitting GSH-AuNCs with an average size of 3.2 ± 0.4 nm and NIR emission quantum yield of 9.9%. Steady-state fluorescence measurements coupled with fluorescence lifetime imaging microscopy (FLIM) assays performed on lyophilized GSH-AuNCs revealed that the obtained GSH-AuNCs exhibit PL emissions at 610 nm (red PL) and, respectively, 800 nm (NIR PL) in both solution and powder solid-state. Time-resolved fluorescence measurements showed that the two PL components are characterized by average lifetimes of 407 ns (red PL) and 1821 ns (NIR PL), respectively. Additionally, due to a partial overlap between the red PL and the absorption of the NIR PL, an energy transfer between the two coexisting emissive centers was discovered and confirmed via steady-state and time-resolved fluorescence measurements. Furthermore, the FLIM analysis performed on powder GSH-AuNCs under 640 nm, an excitation more suitable for bioimaging applications, revealed a homogeneous and photostable NIR PL signal from GSH-AuNCs. Finally, the ability of GSH-AuNCs to operate as reliable NIR-emitting contrast agents inside tissue-mimicking agarose-phantoms was demonstrated here for the first time via complementary FLIM and re-scan confocal fluorescence imaging techniques. In consequence, GSH-AuNCs show great promise for future in vivo imaging applications via confocal fluorescence microscopy.

Cardiac Troponin Biosensor Designs: Current Developments and Remaining Challenges.

Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on electrocardiography (ECG), which has been proven to be insufficient. In this context, the efficient detection of cardiac biomarkers was proposed to overcome the limitations of ECG. In particular, the measurement of troponins, specifically cardiac troponin I (cTnI) and cardiac troponin T (cTnT), has proven to be superior in terms of sensitivity and specificity in the diagnosis of myocardial damage. As one of the most life-threatening conditions, specific and sensitive investigation methods that are fast, universally available, and cost-efficient to allow for early initiation of evidence-based, living-saving treatment are desired. In this review, we aim to present and discuss the major breakthroughs made in the development of cTnI and cTnT specific biosensor designs and analytical tools, highlighting the achieved progress as well as the remaining challenges to reach the technological goal of simple, specific, cheap, and portable testing chips for the rapid and efficient on-site detection of cardiac cTnI/cTnT biomarkers in order to diagnose and treat cardiovascular diseases at an incipient stage.

Photoluminescent Histidine-Stabilized Gold Nanoclusters as Efficient Sensors for Fast and Easy Visual Detection of Fe Ions in Water Using Paper-Based Portable Platform.

Herein is presented a novel and efficient portable paper-based sensing platform using paper-incorporated histidine stabilized gold nanoclusters (His-AuNCs), for the sensitive and selective detection of Fe ions from low-volume real water samples based on photoluminescence (PL) quenching. Highly photoluminescent colloidal His-AuNCs are obtained via a novel microwave-assisted method. The His-AuNCs-based sensor reveals a limit of detection (LOD) as low as 0.2 µM and a good selectivity towards Fe ions, in solution. Further, the fabricated portable sensing device based on paper impregnated with His-AuNCs proves to be suitable for the easy detection of hazardous Fe levels from real water samples, under UV light exposure, through evaluating the level of PL quenching on paper. Photographic images are thereafter captured with a smartphone camera and the average blue intensity ratio (I/I0) of the His-AuNCs-paper spots is plotted against [Fe2+] revealing a LOD of 3.2 µM. Moreover, selectivity and competitivity assays performed on paper-based sensor prove that the proposed platform presents high selectivity and accuracy for the detection of Fe ions from water samples. To validate the platform, sensing assays are performed on real water samples from local sources, spiked with 35 µM Fe ions (i.e., Fe2+). The obtained recoveries prove the high sensitivity and accuracy of the proposed His-AuNCs-paper-based sensor pointing towards its applicability as an easy-to-use, fast, quantitative and qualitative sensor suitable for on-site detection of toxic levels of Fe ions in low-volume real water samples.

Gold nanoclusters performing as contrast agents for non-invasive imaging of tissue-like phantoms via two-photon excited fluorescence lifetime imaging.

Recently, gold nanoclusters (AuNCs) have received considerable scientific interest due to their ability to generate intrinsic photoluminescence (PL), making them suitable for a wide range of applications, such as sensing, biolabeling and bioimaging. Fluorescence lifetime imaging microscopy (FLIM) is an extremely promising technique when it comes to tissue imaging, especially once combined with near-infrared two-photon excitation (TPE) due to deep tissue penetration and improved spatial resolution. In this paper, we carried out an innovative study on the ability of bovine serum albumin stabilized gold nanoclusters (BSA-AuNCs) to perform as reliable label-free contrast agents for the visualization of tissue-like agarose phantoms via TPE-FLIM. We prove that BSA-AuNCs exhibit uniform and reproducible TPE PL in the first biological window, when embedded in phantoms, under 820 nm excitation provided by a Ti:Sapphire pulsed laser. The two-photon origin of the emission signal inside the phantom is demonstrated by the quadratic dependence of the PL intensity on the excitation power. Moreover, we focused on the evaluation of BSA-AuNCs' potential as contrast agents at different concentrations inside phantoms, simulating an ex vivo environment, at three NIR excitation wavelengths, in view of defining the optimal experimental conditions for future real-tissue imaging assays. The present study aims at translating our previous results on the successful performance of BSA-AuNCs as contrast agents for in vitro FLIM imaging, using visible light, towards non-invasive ex vivo NIR imaging applications. Besides the advantageous use of the combined techniques TPE-FLIM, the novelty of our work consists of demonstrating for the first time the capacity of BSA-AuNCs to perform as bright contrast agents inside cancer-tissue mimicking phantoms. We prove that BSA-AuNCs show great promise as fluorescent contrast agents for TPE-FLIM towards image-assisted tumor surgery.

Novel (Phenothiazinyl)Vinyl-Pyridinium Dyes and Their Potential Applications as Cellular Staining Agents.

We report here the synthesis and structural characterization of novel cationic (phenothiazinyl)vinyl-pyridinium (PVP) dyes, together with optical (absorption/emission) properties and their potential applicability as fluorescent labels. Convective heating, ultrasound irradiation and mechanochemical synthesis were considered as alternative synthetic methodologies proficient for overcoming drawbacks such as long reaction time, nonsatisfactory yields or solvent requirements in the synthesis of novel dye (E)-1-(3-chloropropyl)-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium bromide 3d and its N-alkyl-2-methylpyridinium precursor 1c. The trans geometry of the newly synthesized (E)-4-(2-(7-bromo-10-ethyl-10H-phenothiazin-3-yl)vinyl)-1-methylpyridin-1-ium iodide 3b and (E)-1-methyl-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium tetrafluoroborate 3a' was confirmed by single crystal X-ray diffraction. A negative solvatochromism of the dyes in polar solvents was highlighted by UV-Vis spectroscopy and explanatory insights were supported by molecular modeling which suggested a better stabilization of the lowest unoccupied molecular orbitals (LUMO). The photostability of the dye 3b was investigated by irradiation at 365 nm in different solvents, while the steady-state and time-resolved fluorescence properties of dye 3b and 3a' in solid state were evaluated under one-photon excitation at 485 nm. The in vitro cytotoxicity of the new PVP dyes on B16-F10 melanoma cells was evaluated by WST-1 assay, while their intracellular localization was assessed by epi-fluorescence conventional microscopy imaging as well as one- and two-photon excited confocal fluorescence lifetime imaging microscopy (FLIM). PVP dyes displayed low cytotoxicity, good internalization inside melanoma cells and intense fluorescence emission inside the B16-F10 murine melanoma cells, making them suitable staining agents for imaging applications.

Microfluidic platform for integrated plasmonic detection in laminal flow.

In this work, we propose a novel approach to design robust microfluidic devices with integrated plasmonic transducers allowing portability, reduced analysis time through dynamic measurements and high sensitivity. Specifically, the strategy we apply involves two steps: (i) the controlled deposition of gold bipyramidal nanoparticles (AuBPs) onto a functionalized solid glass substrate and (ii) the integration of the as-fabricated plasmonic substrate into a polydimethylsiloxane (PDMS) microfluidic circuit. The localized surface plasmon resonance (LSPR) sensitivity of the plasmonic-microfluidic device was evaluated by monitoring the optical responses at refractive index changes, proving a bulk sensitivity of 243 nm RIU-1 for the longitudinal LSPR band of isolated AuBPs and 150 nm RIU-1 for the band assigned to end-to-end linked nanoparticles. A strong electric field generated in the gaps between AuBPs-due to the generation of the so-called extrinsic 'hot-spots'-was subsequently proved by the volumetric surface enhanced Raman scattering (SERS) detection of molecules in continuous flow conditions by loading the analyte into the microfluidic channel via a syringe pump. In conclusion, our miniaturized portable microfluidic system aims to detect and identify, in real-time with high accuracy, analyte molecules in laminal flow, thus providing a groundwork for further complex biosensing applications.

Surface-enhanced fluorescence imaging on linear arrays of plasmonic half-shells.

Here, we perform a Surface-Enhanced Fluorescence (SEF) intensity and lifetime imaging study on linear arrays of silver half-shells (LASHSs), a class of polarization-sensitive hybrid colloidal photonic-plasmonic crystal unexplored previously in SEF. By combining fluorescence lifetime imaging microscopy, scanning confocal fluorescence imaging, Rayleigh scattering imaging, optical microscopy, and finite difference time domain simulations, we identify with high accuracy the spatial locations where SEF effects (intensity increase and lifetime decrease) take place. These locations are the junctions/crevices between adjacent half-shells in the LASHS and locations of high electromagnetic field enhancement and strong emitter-plasmon interactions, as confirmed also by simulated field maps. Such detailed knowledge of the distributed SEF enhancements and lifetime modification distribution, with respect to topography, should prove useful for improved future evaluations of SEF enhancement factors and a more rational design of efficiency-optimized SEF substrates. These linear arrays of metal-coated microspheres expand the family of hybrid colloidal photonic-plasmonic crystals, platforms with potential for applications in optoelectronic devices, fluorescence-based (bio)chemical sensing, or medical assays. In particular, due to the polarized optical response of these LASHSs, specific applications such as hidden tags for anti-counterfeiting or plasmon-enhanced photodetection can be foreseen.

Assessment of the photothermal conversion efficiencies of tunable gold bipyramids under irradiation by two laser lines in a NIR biological window.

In this work, we present a thorough study on the evaluation of the photothermal conversion efficiencies of gold nanobipyramids (AuBPs) under irradiation by two phototherapeutic laser lines at 785 and 808 nm. Due to fine tunability of the longitudinal localized surface plasmon resonance (LSPR) of AuBPs along the entire biological window, AuBPs have great potential to be applied as efficient photothermal agents in specific hyperthermia applications. Aiming to identify the most suitable AuBPs for each laser line, here we synthetized AuBPs of six different aspect ratios with longitudinal LSPR ranging from 662 to 929 nm and compared their intrinsic photothermal properties in colloidal solutions under laser irradiation at various experimental parameters such as sample volume, optical density and laser power. In addition, the experimental plasmonic resonances of the as-prepared AuBPs were perfectly simulated and their theoretical extinction and absorption cross-sections provided by finite-difference time-domain technique. Finally, we found photothermal conversion efficiencies ranging from 40% to 97% for all AuBPs systems under both NIR irradiation laser lines concluding that for the 785 nm excitation wavelength the AuBPs with longitudinal LSPR at 802 nm are most efficient, whereas in the case of the 808 nm laser line the AuBPs with optical response at 812 nm exhibit the best thermal performance. These studies are crucial for designing AuBPs as effective phototherapy agents acting alone or in combination with other plasmon-based or plasmon-assisted therapies.

Gold NanoBipyramids Performing as Highly Sensitive Dual-Modal Optical Immunosensors.

In this work, we demonstrate the feasibility of gold bipyramidal-shaped nanoparticles (AuBPs) to be used as active plasmonic nanoplatforms for the detection of the biotin-streptavidin interaction in aqueous solution via both Localized Surface Plasmon Resonance and Surface Enhanced Raman Scattering (LSPR/SERS). Our proof of concept exploits the precise attachment of the recognition element at the tips of AuBPs, where the electromagnetic field is stronger, which is beneficial to the surface sensitivity of longitudinal LSPR on the local refractive index and to the electromagnetic enhancement of SERS activity, too. Indeed, successive red shifts of the longitudinal LSPR associated with increased local refractive index reveal the attachment of para-aminothiophenol (p-ATP) chemically labeled Biotin to the Au surface and the specific capture of the target protein by biotin-functionalized AuBPs. Finite-Difference Time-Domain simulations based on the reconstructed index of refraction confirm LSPR measurements. However, the molecular identification of the biotin-streptavidin interaction remains elusive by LSPR investigation alone. Remarkably, we succeeded to complement the LSPR detection with reliable SERS measurements which permitted to (a) certify the molecular identification of biotin-streptavidin interaction and (b) extend the limit of detection of streptavidin in solution toward 10-12 M. Finally, to further probe the possibility to implement the AuBPs as dual LSPR-SERS based immunoassays in solution for real clinical diagnostics, we additionally investigated the AuBP's performance to transduce the specific antihuman IgG- human IgG binding event, providing thus a reference design for building unique plasmonic immunoassays for dual-optical detection of target proteins in aqueous solution.

Designing Efficient Low-Cost Paper-Based Sensing Plasmonic Nanoplatforms.

Paper-based platforms can be a promising choice as portable sensors due to their low-cost and facile fabrication, ease of use, high sensitivity, specificity and flexibility. By combining the qualities of these 3D platforms with the optical properties of gold nanoparticles, it is possible to create efficient nanodevices with desired biosensing functionalities. In this work, we propose a new plasmonic paper-based dual localized surface plasmon resonance⁻surface-enhanced Raman scattering (LSPR-SERS) nanoplatform with improved detection abilities in terms of high sensitivity, uniformity and reproducibility. Specifically, colloidal gold nanorods (GNRs) with a well-controlled plasmonic response were firstly synthesized and validated as efficient dual LSPR-SERS nanosensors in solution using the p-aminothiophenol (p-ATP) analyte. GNRs were then efficiently immobilized onto the paper via the immersion approach, thus obtaining plasmonic nanoplatforms with a modulated LSPR response. The successful deposition of the nanoparticles onto the cellulose fibers was confirmed by LSPR measurements, which demonstrate the preserved plasmonic response after immobilization, as well as by dark-field microscopy and scanning electron microscopy investigations, which confirm their uniform distribution. Finally, a limit of detection for p-ATP as low as 10-12 M has been achieved by our developed SERS-based paper nanoplatform, proving that our optimized plasmonic paper-based biosensing design could be further considered as an excellent candidate for miniaturized biomedical applications.

Influence of COVID-19 on Patients with Esophageal Varices under Prophylactic Endoscopic Band Ligation Therapy.

Background and Objectives: Endoscopic band ligation (EBL) plays a critical role in patients with clinically significant portal hypertension, as variceal eradication (VE) is essential to prevent further variceal upper gastrointestinal bleeding (GI). The emergence of COVID-19 has led to a dramatic reduction in endoscopic activity. Our study aimed to evaluate the effect of COVID-19 on VE, GI, and 6-month mortality of patients treated with prophylactic EBL therapy. In addition, our goal was to identify the risk factors for our proposed outcomes. Methods: A single-center retrospective cohort study included patients with esophageal varices treated with prophylactic EBL therapy between 2017 and 2021. To demonstrate the impact of COVID-19 on two independent groups on prophylactic EBL therapy with 1 year of follow-up, March 2019 was selected as the cut-off date. Clinical, laboratory, and endoscopic data were recovered from electronic reports. Results: Ninety-seven patients underwent 398 prophylactic EBL sessions, 75 men (77.3%) with mean age 59 ± 12 years. Most achieved VE (60.8%), 14.4% had GI bleeding post-therapy, and 15.5% died at 6 months. The rate of variceal obliteration was significantly lower in the pandemic group (40.9% vs. 77.4% in the pre-pandemic group, p = 0.001). Mean number of EBL sessions and pandemic group were independently associated with incomplete VE, while MELD-Na, portal vein thrombosis and failed VE were identified as risk factors associated with mortality at 6 months. Conclusions: Almost 60% of patients in the pandemic group failed to eradicate esophageal varices. Failure to achieve this result conferred a higher risk of GI bleeding and death at 6 months, the latter also significantly associated with the MELD-Na score and portal vein thrombosis. Our study is among the first to demonstrate the impact of COVID-19 in patients receiving prophylactic EBL therapy.

Introdução e objetivos: A laqueação elástica endoscópica (LEE) é crucial nos doentes com hipertensão portal clinicamente significativa, uma vez que permite a erradicação das varizes esofágicas (EVE) que, por sua vez, previne a hemorragia digestiva varicosa. Com o início da pandemia COVID-19, a atividade endoscópica foi drasticamente reduzida. Com este estudo pretendemos avaliar a influência da COVID-19 na EVE, hemorragia gastrointestinal (GI) e mortalidade aos 6 meses dos doentes sob LEE profilática, assim como identificar os seus fatores de risco. Métodos: Estudo de coorte monocêntrico e retrospetivo que incluiu doentes com varizes esofágicas sob LEE profilática entre 2017 e 2021. Para demonstrar o impacto da pandemia COVID-19 em dois grupos independentes sob LEE profilática durante um ano de follow-up, a escolha da data-limite foi Março de 2019. Os dados clínicos, laboratoriais e endoscópicos foram obtidos a partir dos relatórios eletrónicos. Resultados: Noventa e sete doentes cumpriram 398 sessões de LEE, 75 homens (77,3%), com idade média de 59 ± 12 anos. A maioria dos doentes obteve EVE (60,8%), 14,4% desenvolveu hemorragia GI e 15,5% faleceu nos primeiros 6 meses pós-terapêutica. A taxa de EVE foi significativamente inferior no grupo pandémico (40,9% vs. 77,4% no grupo pré-pandémico, p = 0.001). O número médio de sessões de LEE e o grupo pandémico foram independentemente associados à EVE incompleta; enquanto MELD-NA, trombose da veia porta e falha na EVE foram identificados como fatores de risco associados à mortalidade aos 6 meses. Conclusão: Cerca de 60% dos doentes no grupo pandémico não conseguiu erradicar as varizes esofágicas. A EVE incompleta aumenta o risco de hemorragia GI e mortalidade aos 6 meses, esta última também associada de forma significativa ao score MELD-Na e TVP. O nosso estudo foi pioneiro na demonstração do impacto da pandemia COVID-19 nos doentes sob LEE profilática.

Sonochemical synthesis, optical properties and DFT studies on novel (N-arylamino)phenothiazinium dyes suitable for fluorescence cells imaging.

Novel (N-arylamino)phenothiazinium dyes containing meta-substituted-arylamine auxochrome units were successfully obtained by applying a sonochemical protocol designed for a more efficient energy usage in the preparation of methylene blue (MB) analogues. Single crystal X-ray diffraction analysis revealed the spatial arrangement in aggregated crystalline state of (N-(meta-bromoaryl)amino)phenothiazinium dye with minor variances induced by the nature of the halogenide counterion (iodide or chloride). The optical UV-vis properties of the novel (N-arylamino)phenothiazinium dyes were comparable to those of the parent MB, with the longest wavelength absorption maxima situated in the visible range (640-680 nm), large molar extinction coefficients (log ε = 4.5-5.1) and weak solvatochromism in polar solvents. Their fluorescence emission in solid state was evidenced by One Photon Excited Fluorescence Lifetime Imaging (OPE-FLIM) and Two Photon Excited Fluorescence Lifetime Imaging (TPE-FLIM) experiments. Theoretical calculations based on Time Dependent-Density Functional Theory (TD-DFT) at B3PW91 and CAM-B3LYP/def2-SV(P) level of theory predicted absorption and fluorescence emission wavelength maxima in reasonable agreement with experimental data. Computational results suggest that the electronic excitations imply a departure from the planar molecular ground state towards geometrically rearranged excited states disfavoring the vibronic couplings due to a high degree of flexibility induced by the conformational motion of the N-arylamino auxochromes. Preliminary studies regarding the dyes' relevance in biological environment indicated lipophilicity (log P octanol/water 0.5-2.3), no aggregation tendency in diluted solutions in the concentration range 10-50 microM and ability for cytoplasmatic staining of D407 human retinal pigment epithelial cells.

Innovative, Flexible, and Miniaturized Microfluidic Paper-Based Plasmonic Chip for Efficient Near-Infrared Metal Enhanced Fluorescence Biosensing and Imaging.

The implementation of metal enhanced fluorescence (MEF) as an efficient detection tool, especially in the near-infrared region of the electromagnetic spectrum, is a rather new direction for diagnostic analytical technologies. In this context, we propose a novel microfluidic plasmonic design based on paper for efficient MEF detection of the "proof-of-concept" biotin-streptavidin recognition interaction. Our design made use of the benefits of gold nanobipyramids (AuBPs), considering the strong enhanced electromagnetic field present at their sharp tips, and filter paper to operate as a natural microfluidic channel due to excellent wicking abilities. The calligraphed plasmonic paper, obtained using a commercial pen filled with AuBPs, was integrated in a robust sandwich optically transparent polydimethylsiloxane chip, exhibiting portability and flexibility while preserving the chip's properties. To place the Alexa 680 fluorophore at an optimal distance from the nanobipyramid substrate, the human IgG-anti-IgG-conjugated biotin sandwich reaction was employed. Thus, upon the capture of Alexa 680-conjugated streptavidin by the biotinylated system, a 1.3-fold average enhancement of the fluorophore's emission was determined by bulk fluorescence measurements. However, the local enhancement factor was considerably higher with values spanning from 5 to 6.3, as proven by mapping the fluorescence emission under both re-scan microscopy and fluorescence lifetime imaging, endorsing the proposed chip's feasibility for bulk MEF biosensing as well as high-resolution MEF bioimaging. Finally, the versatility of our chip was demonstrated by adapting the biosensing protocol for cardiac troponin I biomarker detection, validated using 10 plasma samples collected from pediatric patients and corroborated with a conventional ELISA assay.