Functional Nanomedicines for Targeted Therapy of Bladder Cancer

Bladder cancer is one of most common malignant urinary tract tumor types with high incidence worldwide. In general, transurethral resection of non-muscle-invasive bladder cancer followed by intravesical instillation of chemotherapy is the standard treatment approach to minimize recurrence and delay progression of bladder cancer. However, conventional intravesical chemotherapy lacks selectivity for tumor tissues and the concentration of drug is reduced with the excretion of urine, leading to frequent administration and heavy local irritation symptoms. While nanomedicines can overcome all the above shortcomings and adhere to the surface of bladder tumors for a long time, and continuously and efficiently release drugs to bladder cancers. The rapid advances in targeted therapy have led to significant improvements in drug efficacy and precision of targeted drug delivery to eradicate tumor cells, with reduced side-effects. This review summarizes the different available nano-systems of targeted drug delivery to bladder cancer tissues. The challenges and prospects of targeted therapy for bladder cancer are additionally discussed.

Do You See What I See? Researcher-Participant Agreement on Single-Item Measures of Emotion Regulation Behaviors in Borderline Personality Disorder

Researchers use ecological momentary assessment (EMA) to study a range of behaviors related to psychopathology. However, it is unclear whether brief measures of coping behaviors accurately capture the intended responses. In this secondary analysis of a single-case experimental design, eight individuals with borderline personality disorder (Mage = 21.57, 63% female, 63% Asian American) completed daily diary entries for 12 weeks, along with hourly EMA entries on 2 days. Participants provided qualitative descriptions of their behaviors and classified them into one of five functional categories. Independent researchers also classified each qualitative description into the same categories. Overall, agreement between participants and researchers was low, Krippendorff’s α = .47, 95% confidence interval [0.43, 0.52]. The type of emotion experienced, researcher confidence, and word count of responses affected agreement. Generating items that capture the breadth of possible behaviors, are brief enough for frequent administration, and are consistently understood by participants is an important continued challenge in EMA research.

Do You See What I See?: Researcher–Participant Agreement on Single-Item Measures of Emotion Regulation Behaviors in Borderline Personality Disorder

Researchers use ecological momentary assessment (EMA) to study a range of behaviors related to psychopathology. However, it is unclear whether brief measures of coping behaviors accurately capture the intended responses. In this secondary analysis of a single-case experimental design, eight individuals with borderline personality disorder ( Mage = 21.57, 63% female, 63% Asian American) completed daily diary entries for 12 weeks, along with hourly EMA entries on 2 days. Participants provided qualitative descriptions of their behaviors and classified them into one of five functional categories. Independent researchers also classified each qualitative description into the same categories. Overall, agreement between participants and researchers was low, Krippendorff’s α = .47, 95% confidence interval [0.43, 0.52]. The type of emotion experienced, researcher confidence, and word count of responses affected agreement. Generating items that capture the breadth of possible behaviors, are brief enough for frequent administration, and are consistently understood by participants is an important continued challenge in EMA research.

P636 The natural history of COVID-19 in patients with IBD: A nationwide study by the Hellenic Society for the Study of IBD

Background COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to the frequent administration of immune-modifying treatments. Methods We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via the unbiased reporting of all cases that were registered during the first and second waves of the pandemic. Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnosis of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies were analysed against adverse outcomes (hospitalization, ICU admission, and death). Results We identified 80 patients with IBD who were diagnosed with COVID-19 during the study period (male:65%; median age=44 [IQR=26] years; CD:62.5%). Adverse outcomes were reported in 16 patients (20%), including 3 ICU admissions (3.75%) and 2 deaths (2.5%). Negative prognostic factors for adverse outcomes included age, Body Mass Index, and hypertension, as well as dyspnoea, fatigue and abdominal pain at presentation. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable course COVID-19. Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous medications. Conclusion Patients with IBD who developed COVID-19 had a benign course with adverse outcomes being scarce. Treatment with biologics had a beneficial effect, supporting the continuation of therapy during the pandemic.

Improving the Solubility, Dissolution, and Bioavailability of Metronidazole via Cocrystallization with Ethyl Gallate

Metronidazole (MTZ) is an antibacterial drug widely used for the treatment of protozoan and anaerobic infections in humans and animals. However, its low bioavailability necessitates the frequent administration of a high dose to attain an effective plasma concentration profile for therapy. To reduce the dose of MTZ, we have prepared a new cocrystal between MTZ and ethyl gallate (EG). The solid-state properties of MTZ-EG were characterized using complimentary techniques, including thermal, spectroscopic, microscopic, and X-ray crystallographic methods. The MTZ-EG cocrystal exhibits a higher solubility and faster dissolution than MTZ. The bioavailability of MTZ in rats was increased by 36% when MTZ-EG was used.

Fabrication and Characterisation of a Photo-Responsive, Injectable Nanosystem for Sustained Delivery of Macromolecules

The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of ≥80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.

A LITERARY REVIEW ON SAPINDUS TRIFOLIATUS (GASPENELA) AND ITS MEDICINAL VALUES

Sapindus trifoliatus is a large tree used in treatment of numerous ailments. Its fruits, known as soap nuts, contain Saponin and are widely used in cosmetics. Fruits, skin of the fruit, seeds and leaves are used in medicine internally and externally. Knowledge on medicinal uses of Sapindus trifoliatus is scattered. Therefore, it was decided to gather and record this dispersed information. Data was collected from Ayurveda and Sri Lankan medical books, journals, physicians and through web search. Sapindus trifoliatus is used to conduct Vamana Karma, Virechana Karma and Nasya Karma. It is used in treatment of migraine, epilepsy, bronchial asthma, cough and burning sensation. It is also used in preparation of body shampoo, hair shampoo and detergents. Anti- ulcer, anthelmintic, anti-inflammatory, muscle relaxant, anti-acne and anti-dandruff effect of Sapindus trifoliatus is scientifically proven. Leaf extract was found to be non-toxic up to 2g/kg but frequent administration in high doses elevate in aspartate aminotransferase, alanine aminotransferase, blood urea and serum creatinine in rats. It is concluded that Sapindus trifoliatus has multifaceted medicinal values.

Evaluation of the Development of Tolerance Following Frequent Administration of Propofol in Children Requiring Successive Sedation for Separate Procedures

OBJECTIVE Propofol is frequently used for outpatient sedation for pediatric patients, some of whom require multiple rounds of sedation for separate procedures within a short period. Anecdotal experience suggests that frequent use of propofol results in escalating doses; however, clinical evidence is unconvincing. This study was designed to evaluate if tolerance develops with frequent administration of propofol for children requiring multiple successive sedations. METHODS A retrospective chart review of patients requiring multiple doses of propofol for separate procedures from 2011 through 2019 was conducted. Cumulative propofol dose and induction dose were analyzed using a mixed model for patients requiring sedation for serial procedures. RESULTS Data from 24 different patients who required 3 or more sedations during the study period were analyzed. The number of sedations ranged from 3 to 28. The mean total propofol dose rate was 0.19 ± 0.14 mg/kg/min, and the mean induction dose was 3.2 ± 0.97 mg/kg. The total doses and induction doses were not statistically significantly different at different sedations (p = 0.089 and 0.180, respectively). There was a statistically significant decrease in the total dose as the time interval between 2 sedations increased (p &lt; 0.001). CONCLUSIONS Repeated administrations of propofol at time intervals used in outpatient sedation do not lead to the development of tolerance. A small decrease per day interval may be significant when propofol is used more frequently (multiple times per day or as a continuous drip) in an ICU setting.

Abstract P556: Emergent Use of Ticagrelor and Glycoprotein IIbIIIa in Neuroendovascular Interventions

Introduction: Evidence regarding the optimal acute antiplatelet strategies in emergent endovascular therapies is scarce, and practices varies institutionally. Ticagrelor, a P2Y3B inhibitor with a lower incidence of resistance, may be effective in achieving rapid platelet inhibition. We explore the safety and efficacy of emergent Ticagrelor use in patient undergoing neurointerventions. Methods: We reviewed our database for all consecutive patients from 2016 to 2019 who received emergent administration of Ticagrelor (within 30 minutes before or after) for neuro-interventional procedures. The primary outcome measure was the incidence of major systemic hemorrhages including symptomatic intracranial hemorrhage as well as intraprocedural and post-procedural thrombotic events. Results: 81 patients were analyzed (Mean age 62±11, 70% male, 73 undergoing interventions for ischemic strokes, 8 aneurysm patients undergoing embolization). Twenty (24.7%) patients received Ticagrelor pre-puncture, 28 (35%) during and 33 (41%) after closure. Median PRU achieved in 43 patients after excluding for concomitant use of GPIIbIIIa use was 54 [36-111]. Major bleeding occurred in 7/81 patients (9.2%) - 4 gastrointestinal bleeding and 3 symptomatic ICH. Eleven (14%) patients experienced intraprocedural occlusions. Five (6.2%) cases were complicated by post-procedural occlusions while on Ticagrelor, two of which were asymptomatic. Pre-procedural Ticagrelor was associated with less frequent administration of subsequent GPIIbIIIa (OR = 0.15, 95% CI (0.03-0.64), p=0.01), as well as shorter procedure duration (Spearman’s rho 0.409, p =0.001). The use of GPIIbIIIa plus Ticagrelor was associated with increased bleeding complications (0% vs. 14%; p =0.04) than in patients receiving Ticagrelor only. Bleeding was an independently predictive risk factor for death by 3 months (OR 7.18, 95% CI (1.33-38.8, p=0.02 or 43% vs. 9.5%; p=0.04) Conclusion: Early and emergent use of Ticagrelor, prior to endovascular procedure as early as within 30 minutes, may obviate the need for administration of GPIIbIIIa. Combined use of GPIIbIIa antithrombotics with Ticagrelor was associated with hemorrhagic complications, which could contribute to increased mortality.