Gold Probes Research Articles

Visual simultaneous detection of single nucleotide polymorphism of tumor susceptibility gene and marker alpha-fetoprotein based on double-labeled colloidal gold probe with lateral flow strip biosensor

Liver cancer is one of the most common cancers in the world. The gene CYP1A1 is closely related to the occurrence of cancer, and the tumor marker alpha-fetoprotein (AFP) is also one of the important indicators for liver cancer screening. Therefore, detection of these two substances is of great significance. In this paper, a test strip biosensor capable of simultaneously detecting cancer susceptibility gene CYP1A1 and AFP has been established. There were two detection lines in the strip biosensor, one was used for qualitative detection of susceptible gene by base complementary pairing, and the other was used for semi-quantitative detection of AFP by antigen-antibody reaction. Finally, signal amplification was achieved by horseradish peroxidase catalyzing substrate 3-amino-9-ethylcarbazole. Results showed that under the optimized conditions, the strip biosensor had a good linear relationship (R2 = 0.987) when AFP concentration was in the range of 20–250 ng/mL, and the other hundred times of proteins had no obvious interference to the detection, indicating that the method presented good selectivity. The detection of susceptibility gene CYP1A1 and AFP in real blood samples by the strip was in accordance the standard method, which showed that the method had good accuracy and could be used for qualitative judgment of SNP locus base type of susceptibility gene and semi-quantitative detection of tumor marker in real sample, so it had a good application potential.

Gold nanocluster-based fluorescence turn-off probe for sensing of doxorubicin by photoinduced electron transfer

Doxorubicin (DOX), an anthraquinone-based anticancer drug, is effective for the treatment of a variety of human tumors. However, due to its narrow therapeutic window, serum levels need to be closely monitored. Herein, we report the development of a novel fluorescence probe based on gold nanoclusters co-modified with dithiothreitol (DTT) and carboxylated chitosan (CC) (CC/DTT-AuNCs) for the determination of DOX. The emission from the CC/DTT-AuNCs is significantly suppressed by DOX. The fluorescence-quenching mechanism involving DOX was systematically explored, and photoinduced electron transfer was identified to play a dominant role. DOX readily binds to the CC/DTT-AuNC surface through electrostatic attraction, after which it accepts the electron from the photoexcited CC/DTT-AuNC and quenches its fluorescence. We found that other anthraquinone structures (e.g., alizarin and emodin) devoid of –NH2 groups exhibited almost no CC/DTT-AuNCs fluorescence-quenching effect due to weak electrostatic interactions between these anthraquinones and the NCs. A linear relationship between photoluminescence suppression and the concentration of DOX was observed in the 0.05–2 μM range under the optimal experimental conditions, with a detection limit as low as 5 nM. This new sensing approach was also used to successfully measure DOX in human serum samples with satisfactory results obtained.

Gold nanoparticle-based plasmonic probe for selective recognition of adenosine

Adenosine, as an endogenous molecule in organisms, plays an essential role in biological processes. Here, a plasmonic probe, creatinine-Ag+/gold nanoparticle (AuNPs), is assembled for adenosine detection based on synergistic coordination on AuNPs. The A650 nm/520 nm values of AuNPs system change linearly with adenosine concentration over a range of 1.0–5.0 μM and the detection limits reached 45 nM. The adenosine detection is realized within 4 min. Furthermore, the quantitative detection of adenosine is realized by eyedropper (a function in Microsoft’s PowerPoint) for analyzing RGB value changes of colorimetric assay. Therefore, this sensor can provide accurate and rapid assay of adenosine in patients’ serum sample without complicated instrumentations.

Gold nanoflower-based surface-enhanced Raman probes for pH mapping of tumor cell microenviroment.

ObjectivesEarly diagnosis of tumour cells is critically important for cancer treatment. Given that the tumour environment is slightly acidic, the pH value of the cell environment can be used as a criterion for tumour diagnosis. However, mapping pH in the cell environment with high resolution, high sensitivity and accuracy remains challenging.Materials and MethodsBased on gold nanoflower as surface‐enhanced Raman scattering (SERS) substrate loading with p‐mercaptobenzoic acid (MPA) as pH‐responsive Raman reporter, a new SERS nanoprobe for pH mapping was developed.ResultsThis probe showed a characteristic Raman spectrum signal in response to the different pH in solutions or cells. The signal intensity is positively correlated to the pH value. Moreover, this probe is self‐correctable, which can help eliminate the influence of probe concentration on the accuracy of pH measuring.ConclusionsWe demonstrate the pH mapping of cell environment using the probe, which can be used to distinguish normal cells and tumour cells. This method may provide a new imaging tool for early diagnosis of cancer.

Integrated immunochromatographic assay for qualitative and quantitative detection of clenbuterol

In this study, colloidal gold (CG) and time-resolved fluorescent nanobead (TRFN) probes were used to establish an integrated immunochromatographic assay (ICA) to qualitatively and quantitatively detect clenbuterol (CLE). The best experimental conditions for the two probes in separate ICAs were obtained by optimizing the antibody labeling concentration, the amount of antigen, and the concentration of probe. When the CG and TRFN probes co-existed in the ICA, the latter had no effect on the sensitivity of qualitative detection of the CG probe-based ICA. However, the CG probe optimized the linear range of quantitative detection in the TRFN probe-based ICA. The integrated test strip can be used for qualitative and quantitative detection of CLE in one step. When the amount of antigen reached 0.4 mg/mL, the CG probe concentration reached 1.2 μg/mL, and the TRFN probe concentration reached 0.68 μg/mL. The qualitative sensitivity of the integrated ICA was 0.5 ng/mL and its quantitative limit of detection was 0.04 ng/mL with a detection range of 0.1–2.7 ng/mL. This developed method is of great significance for large-scale samples screening and positive monitoring in the field of food safety testing.

High-Speed Observations of the Unbinding/Binding Motions of the Leading Head of Kinesin-1 From/To Microtubule Provide Kinetic Evidence for the Front-Head Gating Mechanism

Kinesin-1 is a motor protein that moves processively along microtubule by alternately moving two motor domains (“heads”). To move in the hand-over-hand manner, ATP hydrolysis cycles of the two heads should be coordinated such that the trailing head hydrolyses ATP and detaches from the microtubule before the leading head does. To explain such coordination, the front-head gating model has been proposed that ATP binding or hydrolysis in the leading head is prohibited due to the backward tension posed through the neck linker. However, it has been technically difficult to directly measure the detachment rate of the leading head. Here, we utilized a heterodimer composed of the wild-type head and a E236A mutant head that hydrolyses ATP very slowly. Single molecule FRET observations between dyes attached to two heads showed that the wild-type head spent majority of time in the leading position under saturating ATP condition. Then we attached a 40 nm-ϕ gold particle specifically to the wild-type head and observed its motion using total internal reflection-based dark-field microscopy at 50 μs temporal resolution. At this resolution, we could clearly distinguish microtubule-bound and -unbound states by the difference in the magnitude of fluctuation of the gold probe. The dwell time of the leading head in the microtubule-bound state was 160 ms on average at 1 mM ATP condition, which was significantly larger than the dwell time of a head of wild-type homodimer in the bound state at trailing position (10 ms; Isojima et al. Nat. Chem. Biol. 2016). These results provide kinetic evidence for the front-head gating model.

Photoelectrochemical biosensor for microRNA detection based on a MoS2/g-C3N4/black TiO2 heterojunction with Histostar@AuNPs for signal amplification

Herein, a novel photoelectrochemical (PEC) biosensor was developed for the ultrasensitive detection of microRNA-396a based on a MoS2/g-C3N4/black TiO2 heterojunction as the photoactive material and gold nanoparticles carrying Histostar antibodies (Histostar@AuNPs) for signal amplification. Briefly, MoS2/g-C3N4/black TiO2 was deposited on an indium tin oxide (ITO) electrode surface, after which gold nanoparticles (AuNPs) and probe DNA were assembled on the modified electrode. Hybridization with miRNA-396a resulted in a rigid DNA: RNA hybrid being formed, which was recognized by the S9.6 antibody. The captured antibody can further conjugate with the secondary IgG antibodies of Histostar@AuNPs, thereby leading to the immobilization of horse radish peroxidase (HRP). In the presence of HRP, the oxidation of 4-chloro-1-naphthol (4-CN) by H2O2 was accelerated, producing the insoluble product benzo-4-chlorohexadienone on the electrode surface and causing a significant decrease in the photocurrent. The developed biosensor could detect miRNA-396a at concentrations from 0.5 fM to 5000 fM, with a detection limit of 0.13 fM. Further, the proposed method can also be used to investigate the effect of heavy metal ions on the expression level of miRNAs. Results suggest that the biosensor developed herein offers a promising platform for the ultrasensitive detection of miRNA.

Endoscopic Management of Biliary Stent Occlusion With Bipolar Electrocautery

Persistent biliary obstruction due to stent occlusion is a major cause of morbidity and mortality in patients with malignant obstruction of the bile duct. The standard of care for endoscopic management of these occlusions involves mechanical cleaning with a balloon or additional stent insertion. We present the case of a patient with biliary metal stent occlusion that was successfully treated with the aid of endoscopic bipolar electrocautery. A 73-year-old man with history of metastatic gastrinoma complicated by malignant biliary obstruction presented to the hospital with sepsis and was admitted to the MICU. During his workup, he was found to have rising total bilirubin levels, despite previously having four stent-in-stents placed to maintain patency of the CBD. Imaging was concerning for worsening CBD and intrahepatic biliary duct dilation. During ERCP, the stents were found to be occluded by sludge and debris. After attempted manual debridement with endoscopic forceps, a catheter could not be advanced through the stent occlusion. A bipolar electrocautery probe was then used to tunnel through the occlusion using soft coagulation. After tunneling, a balloon was passed through the inner stent for manual debridement. Occlusion cholangiogram after cleaning demonstrated patency of the duct with good drainage. Self-expanding metal stent placement is the standard therapy for endoscopic treatment of malignant biliary obstruction. Unfortunately, ensuring patency of these stents is difficult. Simple stent occlusions can be treated with a stent-in-stent approach or with mechanical cleaning with a balloon catheter. However, problems can arise that make this approach technically infeasible. With significant tumor ingrowth into the lumen of the stent, or with densely packed debris, a guidewire cannot be passed through the stent. Several studies have highlighted the use of radiofrequency ablation to tunnel through the occlusion. An alternative that has not been studied is the use of bipolar electrocautery to deliver thermal energy directly within the occluded stent. Our case demonstrated that an electrocautery probe can be used in a controlled manner to debride biliary duct occlusions, after which a balloon can be passed for more thorough cleaning. The wide availability of the gold probe catheter, ease of use, and minimal cost, make this a compelling alternative to radiofrequency ablation. Further study is warranted to assess the efficacy and safety of this approach.1414_A.tif Figure 1: Fully occluded uncovered SEMS seen protruding from the ampulla of Vater1414_B.tif Figure 2: Gold Probe catheter was used to burrow through the debris within the stent1414_C.tif Figure 3: After debridement, bile was visualized flowing freely through the stent

An Unexpected Outcome After Coil Embolization for Recurrent Upper Gastrointestinal Bleed

Non-variceal bleeding can have significant morbidity and mortality if not adequately controlled. Endoscopy is the first-line treatment, but 5% to 10% of the time these bleeds require alternate intervention. The role of early elective surgery or angiographic embolization in selected high-risk patients to prevent rebleeding remains controversial. Even after embolization, complications and further bleeding can occur. We report a case of coil migration leading to recurrent bleeding requiring surgical intervention. 45-year-old male with a past medical history of perforated duodenal ulcer post laparoscopic repair with a Graham patch secondary to NSAID and alcohol use presented to Akron City Hospital for hematemesis. Initial EGD showed a large cratered duodenal ulcer with a visible vessel in the duodenal bulb. The visible vessel was spurting blood and therefore epinephrine was injected in four quadrants followed by bipolar gold probe therapy, but the bleeding resolved only after two hemoclips were placed. The bleeding returned and interventional radiology performed a coil embolization of the gastroduodenal artery. About two weeks later, he presented back to the ER with hematemesis and melena with a hemoglobin of 5.9 g/dL [14-18 g/dL]. Repeat EGD showed a large duodenal ulcer with adherent clot and previously placed embolization coil erupting through the mucosa from a branch of the gastroduodenal artery. Bleeding continued from this site as noted by dark red blood from a nasogastric tube and decreasing hemoglobin despite multiple blood transfusions. General surgery was consulted and the concern was that the coil migration was allowing continued bleeding, so they performed a laproscopic vagotomy, antrectomy, with billroth 2 reconstruction. Complication with CBD injury occurred requiring extra surgical intervention. Bleeding finally was controlled with the completion of this surgery. Embolization of the gastroduodenal artery is a safe and effective technique for a bleeding duodenal ulcer however it is important to remember complications occur. The endoscopic view of arterial embolization coils is a rare but known complication. In our case, the migrated coil provided a nidus for continued UGIB and required a complicated surgery to correct. The prognostic value of viewing an embolization coil with regard to re-bleeding incidence remains unclear. Close follow up is needed as re-bleeding can occur warranting further therapies and even surgical interventions.

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl4, FeCl2), whereas Na2SeO3 supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.

Investigation of Coatings for Langmuir Probes in an Oxygen‐Rich Space Environment

AbstractUse of Langmuir probes in the atmospheres of planets is complicated by oxidation of the probe surface when high‐density oxygen atoms/molecules and/or ions are present. Oxidation of most materials creates an electrically resistive layer on the probe surface that reduces the current collected at a given bias voltage, changing the probe's current‐voltage (I‐V) curves and consequently the measured plasma parameters. TiN (Titanium Nitride), DAG (a graphite coating), or Gold are currently used Langmuir probe coatings, yet they all have issues when exposed to oxygen‐rich environments. Iridium and Rhenium are selected as new coating candidates because of the high conductivity of their oxidized forms and high hardness. Here we present the oxidation effect on the measurements of probes made of current coating materials (DAG, Gold, and TiN) and new coating materials (Iridium and Rhenium) against controls (Copper and Nickel) in the laboratory. The oxidation process is performed by bombarding oxygen ions on the probe surface with energies of 1.5–10 eV. The probe's I‐V curves taken in an argon plasma are compared before and after oxidation. Our results show that the TiN, Gold, and DAG probes show significant to small changes in their I‐V curves, while Iridium outperforms all the other testing materials with almost unchanged I‐V curves after the oxidation process. Additionally, this new coating can be applied for other plasma instruments in which surface oxidation may pose an issue. However, for the application of Iridium to electric field probes, future work must be carried out to determine photoemission characteristics.

Gold nanocluster-based ratiometric fluorescent probes for hydrogen peroxide and enzymatic sensing of uric acid

A method is described for ratiometric fluorometric assays of H2O2by using two probes that have distinct response profiles. Under the catalytic action of ferrous ion, the 615nm emission of protein-stabilized gold nanoclusters (under 365nm photoexcitation) is quenched by H2O2, while an increased signal is generated with a peak at 450nm by oxidizing coumarin with the H2O2/Fe(II) system to form a blue emitting fluorophore. These decrease/increase responses give a ratiometric signal. The ratio of the fluorescences at the two peaks are linearly related to the concentration of H2O2 in the range from 0.05 to 10μM, with a 7.7nM limit of detection. The detection scheme was further coupled to the urate oxidase catalyzed oxidation of uric acid which proceeds under the formation of H2O2. This method provides an simple and effective means for the construction of ratiometric fluorometric (enzymatic) assays that involve the detection of H2O2. Graphical abstract Under catalysis byferrous ion, hydrogen peroxide quenches the luminescence of gold nanoclusters (AuNCs) and oxidizes coumarin into a fluorescent derivative, which rendered fluorescence ON and OFF at two distinct wavelengths for ratiometric measurements.

Multispectral Photoacoustic Imaging of Tumor Protease Activity with a Gold Nanocage-Based Activatable Probe.

Tumor proteases have been recognized as significant regulators in the tumor microenvironment, but the current strategies for in vivo protease imaging have tended to focus on the development of a probe design rather than the investigation of a novel imaging strategy by leveraging the imaging technique and probe. Herein, it is the first report to investigate the ability of multispectral photoacoustic imaging (PAI) to estimate the distribution of protease cleavage sites inside living tumor tissue by using an activatable photoacoustic (PA) probe. The protease MMP-2 is selected as the target. In this probe, gold nanocages (GNCs) with an absorption peak at ~ 800nm and fluorescent dye molecules with an absorption peak at ~ 680nm are conjugated via a specific enzymatic peptide substrate. Upon enzymatic activation by MMP-2, the peptide substrate is cleaved and the chromophores are released. Due to the different retention speeds of large GNCs and small dye molecules, the probe alters its intrinsic absorption profile and produces a distinct change in the PA signal. A multispectral PAI technique that can distinguish different chromophores based on intrinsic PA spectral signatures is applied to estimate the signal composition changes and indicate the cleavage interaction sites. Finally, the multispectral PAI technique with the activatable probe is tested in solution, cultured cells, and a subcutaneous tumor model in vivo. Our experiment in solution with enzyme ± inhibitor, cell culture ± inhibitor, and in vivo tumor model with administration of the developed probe ± inhibitor demonstrated the probe was cleaved by the targeted enzyme. Particularly, the in vivo estimation of the cleavage site distribution was validated with the result of ex vivo immunohistochemistry analysis. This novel synergy of the multispectral PAI technique and the activatable probe is a potential strategy for the distribution estimation of tumor protease activity in vivo.

A novel sandwich enzyme-linked immunosorbent assay with covalently bound monoclonal antibody and gold probe for sensitive and rapid detection of bovine β-lactoglobulin.

Bovine milk is a recognized allergenic food source with β-lactoglobulin (BLG) as its major allergen. Reliable detection of BLG epitopes can, therefore, be a useful marker for the presence of milk in processed food products, and for potential allergenicity. At the present, enzyme-linked immunosorbent assays (ELISA) for the detection of BLG are time-consuming and generally not specific to BLG IgE epitopes. In this study, the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-activated anti-BLG IgE epitope monoclonal antibody (mAb 1G9) was covalently bound onto the KOH-treated microtiter plate surface. Using this mAb-bound plate in sandwich combination with biotinylated anti-BLG polyclonal antibody-labeled gold nanoparticles, a linear dynamic range between 31.25 and 64 × 103ngmL-1 with a limit of detection for BLG of 0.49ngmL-1 was obtained, which is 32 times wider and 16 times more sensitive than conventional sandwich ELISA (sELISA). Total recovery of BLG in spiked food samples was found, without matrix effects. Also in partially hydrolyzed infant formulas, the allergenic BLG residues were detected quantitatively. Compared with conventional and commercial BLG detection sELISAs, our sELISA is reliable, highly BLG epitope-specific, user-friendly, and time-saving and allows accurate detection of potentially allergenic residues in different types of processed foods. This improved sELISA protocol can be easily extended to detect other well-identified and characterized food allergens. Graphical abstract IgE epitope mAb-bound plate in sandwich combination with gold probe for sensitive and rapid detection of bovine β-lactoglobulin and its potentially allergenic residues.

Conductive scanning probe microscopy of the semicontinuous gold film and its SERS enhancement toward two-step photo-induced charge transfer and effect of the supportive layer

The semicontinuous gold film, enabling various electronic applications including development of surface-enhanced Raman scattering (SERS) substrate, is investigated using conductive atomic force microscopy (CAFM) and Kelvin probe force microscopy (KPFM) to reveal and investigate local electronic characteristics potentially associated with SERS generation of the film material. Although the gold film fully covers the underlying silicon surface, CAFM results reveal that local conductivity of the film is not continuous with insulating nanoislands appearing throughout the surface due to incomplete film percolation. Our analysis also suggests the two-step photo-induced charge transfer (CT) play the dominant role in the enhancement of SERS intensity with strong contribution from free electrons of the silicon support. Silicon-to-gold charge transport is illustrated by KPFM results showing that Fermi level of the gold film is slightly inhomogeneous and far below the silicon conduction band. We propose that inhomogeneity of the film workfunction affecting chemical charge transfer between gold and Raman probe molecule is associated with the SERS intensity varying across the surface. These findings provide deeper understanding of charge transfer mechanism for SERS which can help in design and development of the semicontinuous gold film-based SERS substrate and other electronic applications.

Semiquantitative dot-blot immunogold assay for specific detection of white spot syndrome virus.

A dot-blot immunogold assay (DBIA) was developed to detect white spot syndrome virus (WSSV) using the polyclonal antibody VP26 (anti-VP26). The anti-VP26 was immobilized on gold nanoparticles (Ab-AuNPs), and a nitrocellulose membrane was used as a detection pad. When the target WSSV bound to the Ab-AuNPs a reddish dot appeared on the surface of the membrane used within 2-5 Min, which could be seen with the naked eye. The test was able to detect WSSV at concentrations as low as 105 copies μL-1 of WSSV. The DBIA developed had good specificity, and the colloidal gold probe can be applied within 2-3 days when stored at 4°C. For real sample analysis, the DBIA was applied to samples of seawater used for shrimp cultivation without sample preparation. The results indicate that sample 1 showed a positive result, whereas samples 2 and 3 produced negative results. Then, samples 2 and 3 were spiked with WSSV for method validation. To confirm the performance of the DBIA developed, polymerase chain reaction (PCR) was conducted and the PCR results were the same as those found by the DBIA. Therefore, the DBIA developed could be applied for WSSV detection in real water samples.

Gold nanostar-enhanced chemiluminescence probe for highly sensitive detection of Cu(II) ions

Gold nanostars have interesting and unique surface plasmonic properties originating from their multi-branched shape with sharp tips. We demonstrate here the first use of gold nanostars in chemiluminescence (CL) field by studying their effect on H2O2-IO4− reaction. Nanostars, prepared by seed-mediated growth in poly(vinylpyrrolidone) solution in DMF, remarkably enhance the CL intensity of this reaction. On the basis of some evidence- we show that the enhancing effect of gold nanostars is most probably due to the coupling of CL emission to surface plasmons of nanostar tips. We applied the gold nanostar-based CL system as an ultrasensitive and selective probe for detection of nM levels of Cu(II) ions. The probe has a linear calibration range from 2.0nM to 9.0μM with a detection limit of 0.9nM. The developed CL method was validated by analysis of a certified reference material and applied for real environmental and biological samples.

A Rare Cause of Acquired Von Willebrand Syndrome Resulting in Gastrointestinal Bleeding

Von willebrand disease (vWD) is the most common congenital bleeding disorder but acquired von willebrand syndrome (AVWS) is rare. Pathogenesis of AWVS is complex and not fully understood. We report the case of a patient with chronic gastrointestinal bleeding and AVWS from a myeloproliferative neoplasm. A 59-year-old female with a two year history of gastrointestinal bleeding, angioectasia and recurrent hospitalizations for transfusion-dependent anemia presented with a 3 day history of melena. Two weeks prior to presentation, she had an extended upper endoscopy which revealed angioectasias in the jejunum that were cauterized with gold probe. Medications included omeprazole daily and ferrous sulfate three times daily. On arrival, vital signs were stable. Physical exam was remarkable for heart murmur and melena. Abnormal labs included hemoglobin 6.4g/dL and partial prothrombin time 38 seconds. Deep enteroscopy showed a single actively bleeding angioectasia in the proximal jejunum treated successfully with argon plasma coagulation (Fig 1). Heart murmur prompted a von willebrand factor (vWF) panel and echocardiogram. Echocardiogram was normal but ristocetin cofactor, vWF activity, vWF antigen, and factor 8 levels were low. vWF multimers were barely detectable. Further workup included a bone marrow aspiration that confirmed prefibrotic myelofibrosis myeloproliferative neoplasm, AVWS was diagnosed. She was discharged home in stable condition and has been closely monitored by hematology for her myeloproliferative neoplasm. She has not required any further blood transfusions. AVWS is due to a deficiency in the quality or quantity of vWF. The true incidence is unknown since many patients are asymptomatic and therefore undiagnosed. AVWS is characterized by a negative personal and family history of previous bleeding. It is typically seen in the elderly. Angioectasias have been reported in 2-4% of patients with vWD. Management relies on therapy of the underlying process. This case highlights an interesting presentation of a patient with recurrent gastrointestinal bleeding from AVWS secondary to a myeloproliferative neoplasm. Gastroenterologists should be cognizant of this phenomenon as early diagnosis is crucial for appropriate management.Figure: Actively bleeding angiodysplastic lesion in the proximal jejunum.

Endoscopic Treatment of Hyperplastic Gastric Polyp Presenting as Acute Gastrointestinal Bleed

Hyperplastic polyps are seen in approximately 1% of upper gastrointestinal endoscopies. Rarely, they have been implicated in cases of severe gastrointestinal bleeding. We present a case of acute upper gastrointestinal bleed from hyperplastic polyps in a patient taking rivaroxaban and aspirin. An 83-year-old male with a past medical history of atrial fibrillation, on rivaroxaban and aspirin, presents after several episodes of melanotic stool and hematemesis. The patient reported progressive weakness and fatigue over a two week period. The patient had no history of proton pump inhibitor use or H. pylori infection. Admission hemoglobin and platelets were 6.6 g/dL and 87,000. Antiplatelet and anticoagulation therapy was held and the patient was transfused three units of red blood cells and one set of platelets. Intravenous proton pump inhibitors were initiated. Upper endoscopy revealed bright red blood throughout the gastric cavity with active bleeding from a 1.5 cm pedunculated gastric polyp located in the greater curvature of the stomach. Heater probe coagulation with a 7-French gold probe catheter was applied to the site. The site continued to seep and two endoclips were placed at the base of the polyp with control of bleeding (Figure 1). The patient continued to require blood transfusions over the next two days. On hospital day four, a second endoscopy was performed and two additional 0.5 cm hemorrhagic polyps were found and treated with hot snare polypectomy and endoclips (Figure 2). Pathology report revealed hyperplastic polyps (Figure 3). Upon discussion and assessment of the patient's risks, benefits and preferences, the decision was made to resume rivaroxaban and aspirin. At three month follow-up, the patient reported no further episodes of bleeding. The combination of (1) advanced age, (2) presence of polyps and (3) use of oral anticoagulation and/or antiplatelet agents expectedly increases a patient's risk for gastrointestinal bleeding. Case studies involving bleeding due to hyperplastic polyps with an attributed cause linked to oral anticoagulants appear to be positively correlated with survival. In this patient's case, no reversal agent was yet available. However, cessation of medications and endoscopic intervention appeared adequate in providing symptom resolution. Ongoing studies are investigating the benefits of direct Xa inhibitor reversal. Data from these studies may further optimize the treatment of acute gastrointestinal bleeding.FigureFigureFigure

Dieulafoyʼs Lesion in the Esophagus: A Rare Cause of Upper Gastrointestinal Bleed

Dieulafoy's lesions account for about 1.5% of acute upper gastrointestinal (GI) bleeding and have a propensity to cause massive hemorrhage with a high mortality rate of about 80%. A Dieulafoy's lesion is a dilated, aberrant, submucosal artery eroding the overlying mucosa with no underlying ulcer, aneurysm, or intrinsic mural abnormality. The lesion is most commonly located in lesser curvature of the stomach, with rare occurrences in the esophagus. There have been about 280 published case reports in literature, but only 2 of these reports describe Dieulafoy's lesions in the esophagus. A 55-year-old male presented to the emergency department with a three-day history of melena and a near-syncopal episode. Upon presentation, he had a large amount of hematemesis followed by a syncopal episode. The patient required two units of packed red blood cells (PRBC) and aggressive intravenous fluid resuscitation. He was subsequently transferred to the intensive care unit (ICU) for close monitoring. Emergent endoscopy was performed at the bedside which revealed a visible submucosal vessel in distal esophagus suggestive of a Dieulafoy's lesion. It was sclerosed using an injection of epinephrine and complete obliteration of the vessel was achieved using gold probe cautery. Patient's symptoms of GI bleeding resolved and was discharged home. He was recommended to follow up outpatient for subsequent endoscopy in 8 weeks. Dieulafoy's lesions were first reported by Gallard in 1884, and were more precisely reviewed by Georges Dieulafoy. These lesions are commonly called caliber-persistent arteries. They are most commonly found in the stomach (prevalence 75-90%), but are exceedingly rare in the esophagus (prevalence 8%). Patients most commonly present with hematemesis and melena. Endoscopy has become the mainstay of diagnosis and treatment. The endoscopist may choose to use clipping, thermocoagulation, or to inject epinephrine into the lesion like in our case. Endoscopy has a 70% sensitivity, and if it fails to diagnose the lesion, angiography may be employed and the lesion may be embolized. If minimally invasive approaches fail, surgery is reserved as a last resort. Although Dieulafoy's lesions are exceedingly rare in the esophagus, the high mortality associated with it goes undiscovered and its amenability to life-saving endoscopic therapy prompts us to keep this as a possible differential diagnosis for an upper GI bleed.