Regular Dose Research Articles

Bicalutamide Elicits Renal Damage by Causing Mitochondrial Dysfunction via ROS Damage and Upregulation of HIF-1.

Combined androgen blockade using bicalutamide (Bic) is a therapeutic choice for treating prostate cancer (PCa). However, even at regular clinical dosages, Bic frequently shows adverse effects associated with cardiovascular and renal damage. Previously, we found that Bic selectively damaged mesangial cells compared to tubular cells and in an in vivo rat model, we also found renal damage caused by Bic. In the present study, a rat mesangial cell model was used to further the investigation. Results indicated that Bic enhanced lactate dehydrogenase release, reactive oxygen species (ROS) production, lysosome population and kidney injury molecule-1 and decreased N-cadherin. Bic elicited mitochondrial swelling and reduced the mitochondrial potential, resulting in severe suppression of the oxygen consumption rate (OCR), maximum respiration and ATP production. The hypoxia-inducible factor (HIF)-1α transcriptional activity and messenger RNA were significantly upregulated in dose-dependent manners. The HIF-1α protein reached a peak value at 24 h then rapidly decayed. BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 and cleaved caspase-3 were dose-dependently upregulated by Bic (60 μM) and that eventually led to cell apoptosis. It is suggested that Bic induces renal damage via ROS and modulates HIF-1α pathway and clinically, some protective agents like antioxidants are recommended for co-treatment.

Re-Evaluation of the Size Limitation in Single-Session Stereotactic Radiosurgery for Brain Arteriovenous Malformations: Detailed Analyses on the Outcomes with Focusing on Radiosurgical Doses.

Single-session stereotactic radiosurgery (SRS) for large arteriovenous malformations (AVMs) ≥10 mL remains controversial, which is considered as the current size limitation. To reconsider the size limitation of SRS for AVMs by profoundly analyzing dose-volume relationship. Data on 610 consecutive patients with AVM treated with SRS using regular (18-22 Gy) or low (<18 Gy) prescription doses were retrospectively analyzed. AVMs were classified into 4 groups: small (<5 mL), medium (≥5 and <10 mL), medium-large (≥10 and <15 mL), and large (≥15 mL). The maximum volumes were 22.5 mL (regular-dose group) and 23.5 mL (low-dose group). When treated with regular doses, the cumulative 6-yr obliteration rates for each of the 4 AVM groups were 86%, 80%, 87%, and 79%, respectively; the cumulative 10-yr significant neurological event (SNE) rates were 2.6%, 3.9%, 6.8%, and 5.3%, respectively. Regarding large AVMs, regular-dose SRS resulted in marginally better obliteration rate (6-yr cumulative rate, 79% vs 48%, P=.111) and significantly lower SNE (5-yr cumulative rate, 5% vs 31%, P=.038) and post-SRS hemorrhage rate (8-yr cumulative rate, 0% vs 54%, P=.002) compared to low-dose SRS. Multivariate analyses revealed that regular-dose SRS significantly contributed to increase in the obliteration rate and decrease in SNEs and hemorrhage. The outcomes for large AVMs were generally favorable when treated with ablative doses. Single-session SRS could be acceptable for AVMs up to ≈20 mL if treated with ablative doses.

Factor Xa inhibitors in patients with continuous-flow left ventricular assist devices.

Warfarin is standard anticoagulation therapy for patients with a continuous-flow left ventricular assist device (CF-LVAD). However, warfarin requires regular monitoring and dosage adjustments and fails for many patients, causing thromboembolic and bleeding events. Factor Xa inhibitors have been shown to be noninferior to warfarin in preventing strokes and are associated with less intracranial hemorrhage in patients with atrial fibrillation. We evaluated treatment safety and effectiveness in CF-LVAD patients who switched from warfarin to a factor Xa inhibitor (apixaban or rivaroxaban) after warfarin failure. This was a retrospective, single-center study of patients treated between 2008 and 2018. We assessed the occurrence of stroke, non-central nervous system (CNS) embolism, pump thrombosis, and major gastrointestinal bleeding and intracranial hemorrhage during therapy. We identified seven patients: five were male, the average body mass index was 30kg/m2, and average age was 56years. Preimplantation comorbidities included hypertension (all patients) and diabetes mellitus, ischemic cardiomyopathy, atrial fibrillation, and previous myocardial infarction (fourpatients each). Overall, patients received warfarin for 3968days and apixaban/rivaroxaban for 1459days. The warfarin group was within the therapeutic INR range (2.0-3.0) 30% of the time. Complication rates did not differ between warfarin and apixaban/rivaroxaban: strokes, 0.20 vs none, non-CNS embolism, 0.54 vs none; pump thrombosis, 0.27 vs none; major gastrointestinal bleeding, 0.20 vs 0.50; intracranial hemorrhage, 0.13 vs none. Factor Xa inhibitors may be viable treatment options for CF-LVAD patients for whom warfarin therapy has failed. Large prospective studies are necessary to confirm these results.

Encephalitozoon cuniculi Genotype III Evinces a Resistance to Albendazole Treatment in both Immunodeficient and Immunocompetent Mice.

Of four genotypes of Encephalitozoon cuniculi, E. cuniculi genotype II is considered to represent a parasite that occurs in many host species in a latent asymptomatic form, whereas E. cuniculi genotype III seems to be more aggressive, and infections caused by this strain can lead to the death of even immunocompetent hosts. Although albendazole has been considered suitable for treatment of Encephalitozoon species, its failure in control of E. cuniculi genotype III infection has been reported. This study determined the effect of a 100× recommended daily dose of albendazole on an Encephalitozoon cuniculi genotype III course of infection in immunocompetent and immunodeficient mice and compared the results with those from experiments performed with a lower dose of albendazole and E. cuniculi genotype II. The administration of the regular dose of abendazole during the acute phase of infection reduced the number of affected organs in all strains of mice and absolute counts of spores in screened organs. However, the effect on genotype III was minor. Surprisingly, no substantial effect was recorded after the use of a 100× dose of albendazole, with larger reductions seen only in the number of affected organs and absolute counts of spores in all strains of mice, implying variations in albendazole resistance between these Encephalitozoon cuniculi genotypes. These results imply that differences in the course of infection and the response to treatment depend not only on the immunological status of the host but also on the genotype causing the infection. Understanding how microsporidia survive in hosts despite targeted antimicrosporidial treatment could significantly contribute to research related to human health.

Cerebral computed tomographic angiography using third-generation reconstruction algorithm provides improved image quality with lower contrast and radiation dose.

We hypothesized that cerebral CT angiogram performed using third-generation reconstruction algorithm and lower contrast dose-low-kVp technique (LD-CTA) will provide better image quality when compared with regular contrast dose CTA at 120kVp using a sinogram-affirmed iterative reconstruction algorithm (ND-CTA). Retrospective imaging review of 100 consecutive patients (50 each in LD- and ND-CTA groups). Two readers independently assessed the subjective image quality across multiple vascular segments on a Likert-like scale. Differences in contrast dose, CT dose index (CTDI), and dose length product (DLP) were compared using Mann-Whitney U test. Fisher's exact test was used to compare subjective image quality. Similarly, contrast- and signal-to-noise ratios (CNR and SNR) were compared inthe mid-M1 MCA vessels bilaterally and the mid-basilar artery using Mann-Whitney U test. Interclass correlation coefficient (ICC) was calculated for the SNR/CNR values. Both observers showed excellent correlation in subjective image quality (mean percentage agreement of 95.2% for group 1 versus 89.2% for group 2). LD-CTA group showed better SNR and CNR (p < 0.0001) for both MCA vessels and the mid-basilar artery. Interclass correlation coefficient showed moderate correlation (0.51-0.63) between readers. LD-CTA group also used lower contrast (49cc versus 97cc in ND-CTA) and had lower radiation exposure (DLP/CTDI for both groups 268.3/80.7 vs 519.5/36.08, both < 0.0001). Next-generation reconstruction algorithm and low-kV scanning significantly improved image quality on cerebral CTA images despite lower contrast dose and, in addition, have lower radiation exposure.

Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial

Type 1 diabetes is a common autoimmune disease due to destruction of pancreatic β cells, resulting in lifelong need for insulin. Evidence suggest that maintaining residual β-cell function can improve glucose control and reduce risk of hypoglycaemia and vascular complications. Non-clinical, preclinical and some preliminary clinical data suggest that low-dose interleukin-2 (IL-2) therapy could block pancreatic β cells destruction by increasing the number of functional regulatory T cells (Tregs) that inhibit islet-specific autoreactive effector T cells (Teffs). However, there is lack of data on the effect of low-dose IL-2 in newly diagnosed children and adolescents with T1D as well as lack of specific data on its potential effect on β-cell function. The ‘ Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)’ is a phase 2, multicentre, double-blind, randomised, placebo-controlled trial in children and adolescents (6-18 years; having detectable C-peptide) initiated within 6 weeks of T1D diagnosis. A total of 45 participants will be randomised in a 2:1 ratio to receive either ultra-low dose IL-2 (aldesleukin), at a dose of 0.2 x 10 6 IU/m 2 twice-weekly, given subcutaneously, or placebo, for 6 months. The primary objective is to assess the effects of ultra-low dose aldesleukin administration on endogenous β-cell function as measured by frequent home dried blood spot (DBS) fasting and post-prandial C-peptide in children and adolescents with newly diagnosed T1D. The secondary objectives are: 1) to assess the efficacy of regular dosing of aldesleukin in increasing Treg levels; 2) to confirm the clinical safety and tolerability of ultra-low dose aldesleukin; 3) to assess changes in the immune system indicating benefit or potential risk for future gains/loss in β-cell function and immune function; 4) to assess treatment effect on glycaemic control. Trial registration: EudraCT 2017-002126-20 (06/02/2019)

The evidence-based taibuvid nutritional treatment for minimizing COVID-19 fatalities and morbidity and eradicating COVID-19 pandemic: a novel approach for better outcomes (a treatment protocol)

With the continuously expanding terrible pandemic of COVID-19 infection, globally increasing numbers of COVID-19 patients and contacts progressively jump to heavy burdens beyond capabilities. Developing and poor countries may face humanity disasters in the next few days unless urgent measures are rapidly performed. Standard anti-COVID-19 treatment should inhibit COVID-19 replication, repair virus-induced tissue damage and enhance patients' immunity. Unfortunately, such criteria are still lacking in current treatments resulting in relatively high viral infectivity, morbidity and mortality. Based on previous prophetic medicine research experience and the modern literature, we introduce TaibUVID therapy as a novel evidence-based medicinal nutritional treatment for eradicating COVID-19 pandemic. TaibUVID stands for Taibah University anti-COVID-19 treatment as a novel evidence-based approach (using natural products) for treating COVID-19 patients. A single TaibUVID dose includes: 1 small spoonful (tea spoonful) of nigella sativa oil (or 2 gram nigella sativa seeds) mixed with 1 gram of grinded anthemis hyalina mixed with 1 large spoonful of natural honey. This mixture is to be chewed in the mouth and swallowed orally for both COVID-19 contacts and patients. We adjusted dosing regimen and period of treatment into three clinical levels including contacts or prophylaxis, mild cases and severe case (with pneumonia and ventilated patients). We also introduce novel nigella sativa oil (or nigella sativa decoction) nebulization for local treatment of pneumonia or bronchopneumonia that is faced in severe COVID-19 cases. Such nebulization exerts pulmonary tissue protection and antiviral effects particularly for ventilated patients. The wonderful report by Ulasli et al. (Ulasli et al. Mol Biol Rep. 2014; 41: 1703-11) deserves a lot of interest where nigella sativa and Anthemis hyalina (chamomile) were confirmed to inhibit corona virus replication maximally. In addition, nigella sativa enhances immunity, exerts tissue protective effects and effectively treats co-morbidities. Oral honey exerts potent antiviral effects, enhances immunity and exerts tissue protective effects. TaibUVID Plus dose includes regular TaibUVID dose plus nigella sativa decoction nebulization ± (if possible Clove oil nebulization/ anthemis hyalina decoction nebulization). Clove oil nebulization is beneficial for difficult berating in some COVID-19 cases as clove is confirmed to exert potent antiviral effects. Our suggested TaibUVID and TaibUVID Plus are promising evidence-based approach to rescue lives, decrease fatalities and put a rapid end to COVID-19 pandemic. In prophetic medicine, Prophet Muhammad peace be upon him recommended treatment using both nigella sativa and oral honey saying: In the black cumin (nigella sativa), there is a cure for every disease except death and said also: Cure is in three: in shartat mihjam, gulp of honey (oral honey), and cauterization. I do not recommend my nation to cauterize.

MP42-01 SCATTER RADIATION EXPOSURE TO THE SURGICAL TEAM DURING SUPINE AND PRONE PERCUTANEOUS NEPHROLITHOTRIPSY

You have accessJournal of UrologyImaging/Radiology: Uroradiology II (MP42)1 Apr 2020MP42-01 SCATTER RADIATION EXPOSURE TO THE SURGICAL TEAM DURING SUPINE AND PRONE PERCUTANEOUS NEPHROLITHOTRIPSY David Chapman*, Shubha De, and Devin Demitor David Chapman*David Chapman* More articles by this author , Shubha DeShubha De More articles by this author , and Devin DemitorDevin Demitor More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000891.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radiation is central to diagnostic and therapeutic procedures in Urology. Intraoperative exposure to patients and the care team continues to be a concern. Many strategies help reduce radiation exposure during percutaneous nephrolithotomy (PCNL), however, little has been studied in the contribution of patient positioning and C-arm orientation. The aim of this study was to compare the radiation exposure to the surgical team during supine and prone positions with common C-arm configurations. METHODS: A benchtop experiment was conducted using a Siemens C-arm, anthropomorphic model (80kg human torso) and a 180cc ionization chamber (RadCal Accu Gold Touch) to directly measure radiation scatter (mR/min) to the healthcare team during different configurations of the C-arm (AP, 150 oblique, lateral) for prone and supine (Bart’s free flank 150 decubitus) PCNL. Exposure was measured using regular and high dose fluoroscopy settings, for all personnel [radiation technologist (XRT), scrub nurse (SN), urologist (URO), and anesthesiologist (ANS)] for six c-arm orientations at eye and gonad level. RESULTS: Standard radiation dose was defined as detected scatter with the patient in traditional proned position, and c-arm in AP (eyes: URO 0.59, ANS 0.00, SN 0.00, XRT 0.00 mR/min; gonads URO 1.3, ANS 0.00, SN 0.22, XRT 0.00 mR/min). With the c-arm in lateral orientation and patient in supine, the average dose increased by 6.49 to 21.13 times compared to the oblique and AP configuration, respectively (see figure 1). When dose reduction methods were employed: positioning the surgical team opposite to the image intensifier, exposure was reduced by 3.14-3.58 times, whereas rotating the C-arm over the table (into lateral position) reduced exposure by 1.49-1.46 times (as compared to standard ‘under the table’ lateral positioning). CONCLUSIONS: Radiation is of increasing concern and current guidelines do not recommend physical strategies of dose reduction. This study highlights the ability for a surgical team to drastically alter radiation exposure by considering positioning as part of the contributing factors. Knowing relative exposure increases may empower surgeons to choose alternative orientations to accomplish tasks while minimizing scatter. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e603-e603 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Chapman* More articles by this author Shubha De More articles by this author Devin Demitor More articles by this author Expand All Advertisement PDF downloadLoading ...

Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial.

Type 1 diabetes is a common autoimmune disease due to destruction of pancreatic β cells, resulting in lifelong need for insulin. Evidence suggest that maintaining residual β-cell function can improve glucose control and reduce risk of hypoglycaemia and vascular complications. Non-clinical, preclinical and some preliminary clinical data suggest that low-dose interleukin-2 (IL-2) therapy could block pancreatic β cells destruction by increasing the number of functional regulatory T cells (Tregs) that inhibit islet-specific autoreactive effector T cells (Teffs). However, there is lack of data on the effect of low-dose IL-2 in newly diagnosed children and adolescents with T1D as well as lack of specific data on its potential effect on β-cell function. The ' Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)' is a phase 2, multicentre, double-blind, randomised, placebo-controlled trial in children and adolescents (6-18 years; having detectable C-peptide) initiated within 6 weeks of T1D diagnosis. A total of 45 participants will be randomised in a 2:1 ratio to receive either ultra-low dose IL-2 (aldesleukin), at a dose of 0.2 x 10 6 IU/m 2 twice-weekly, given subcutaneously, or placebo, for 6 months. The primary objective is to assess the effects of ultra-low dose aldesleukin administration on endogenous β-cell function as measured by frequent home dried blood spot (DBS) fasting and post-prandial C-peptide in children and adolescents with newly diagnosed T1D. The secondary objectives are: 1) to assess the efficacy of regular dosing of aldesleukin in increasing Treg levels; 2) to confirm the clinical safety and tolerability of ultra-low dose aldesleukin; 3) to assess changes in the immune system indicating benefit or potential risk for future gains/loss in β-cell function and immune function; 4) to assess treatment effect on glycaemic control. Trial registration: EudraCT 2017-002126-20 (06/02/2019).

Model-Based Biomarker Selection for Dose Individualization of Tyrosine-Kinase Inhibitors.

Tyrosine-kinase inhibitors (TKIs) demonstrate high inter-individual variability with respect to safety and efficacy and would therefore benefit from dose or schedule adjustments. This study investigated the efficacy, safety, and economical aspects of alternative dosing options for sunitinib in gastro-intestinal stromal tumors (GIST) and axitinib in metastatic renal cell carcinoma (mRCC). Dose individualization based on drug concentration, adverse effects, and sVEGFR-3 was explored using a modeling framework connecting pharmacokinetic and pharmacodynamic models, as well as overall survival. Model-based simulations were performed to investigate four different scenarios: (I) the predicted value of high-dose pulsatile schedules to improve clinical outcomes as compared to regular daily dosing, (II) the potential of biomarkers for dose individualizations, such as drug concentrations, toxicity measurements, and the biomarker sVEGFR-3, (III) the cost-effectiveness of biomarker-guided dose-individualizations, and (IV) model-based dosing approaches versus standard sample-based methods to guide dose adjustments in clinical practice. Simulations from the axitinib and sunitinib frameworks suggest that weekly or once every two weeks high-dosing result in lower overall survival in patients with mRCC and GIST, compared to continuous daily dosing. Moreover, sVEGFR-3 appears a safe and cost-effective biomarker to guide dose adjustments and improve overall survival (€36 784.- per QALY). Model-based estimations were for biomarkers in general found to correctly predict dose adjustments similar to or more accurately than single clinical measurements and might therefore guide dose adjustments. A simulation framework represents a rapid and resource saving method to explore various propositions for dose and schedule adjustments of TKIs, while accounting for complicating factors such as circulating biomarker dynamics and inter-or intra-individual variability.

Effect of electron radiation on small-signal parameters of NMOS devices at mm-wave frequencies

The effect of electron radiation on the forward-active small-signal model parameters for 0.35 μm CMOS devices is reported. Four devices with different gate widths were exposed to electron radiation using a Strontium 90 (Sr 90) radiation source at dose rates of 200 kRad (Si)/hr up to a total radiation dose of 2.7 MRad. S-parameters were measured, and small-signal models extracted, both pre-irradiation and at regular dose intervals. Relationships between small-signal model parameters and total radiation dose d were derived and used to calculate small-signal parameters. The major model variations due to total ionizing dose exposure were increases in the gate resistance (Rg), gate drain capacitance (Cgd) and gate source capacitance (Cgs), with a reduction in transconductances (gm and gds). This results in S11 and S22 becoming more resistive as d is increased, with a decrease in the unilateral gain, fT and fmax. The application of the data in predictive modelling of radiation damage is demonstrated.

Enoxaparin dosing in Noonan syndrome: a case report

AbstractBackgroundNoonan syndrome is a genetic condition that typically includes heart abnormalities and characteristic facial features. Various bleeding disorders have been associated with Noonan syndrome. Some affected individuals have excessive bruising, nosebleeds or prolonged bleeding following injury or surgery. This paper describes anti‐Factor Xa levels following excessive enoxaparin dosing in a male patient with Noonan syndrome.Clinical detailsA 24‐year‐old male (weighing 53 kg) presented under Orthopaedics for his elective three‐stage scoliosis surgery for kyphoscoliosis. The patient was usually on warfarin for a mechanical valve replacement. Bridging enoxaparin was prescribed (initially 1.5 mg/kg, SC, daily), but failure to reach therapeutic anti‐Factor Xa levels (highest level 0.44 units/mL) resulted in escalating enoxaparin doses (90 mg, SC, twice daily).OutcomesDespite a doses of up to 1.7 mg/kg enoxaparin twice daily, the patient did not reach therapeutic anti‐Factor Xa levels according to recommended reference ranges. The patient’s regular warfarin dose was restarted and the enoxaparin was ceased once his International Normalised Ratio was within the therapeutic range. The patient was transferred to a a rehabilitation facility 10 days after surgery.ConclusionMedication assay ranges may not always be an accurate point of reference, particularly when patients present with unusual comorbidities. As health care moves towards patient‐centred care, it is essential that individual patient parameters are considered when monitoring medication treatment plans.

Regular Doses of Nature: The Efficacy of Green Exercise Interventions for Mental Wellbeing.

This study investigated the efficacy of medium-term Green Exercise (GE; being physically active within a natural environment) interventions for improving wellbeing, by pooling data collected at the start and end of participants’ engagement with a range of GE interventions. Hypotheses were that (i) interventions would show good efficacy for improving wellbeing in the overall sample; (ii) compared to participants reporting ‘average to high’ wellbeing at the start of their project, participants with ‘low’ starting wellbeing would report greater improvements post-intervention; and (iii) improvements would significantly differ between age groups. The pooled dataset was categorized in line with UK norms (n = 318) and analyzed using a standardized meta-analysis approach. Effect size was large: g = 0.812 (95% CI [0.599, 1.025]), and differences in wellbeing changes associated with project duration, age or sex were not statistically significant. Compared to those reporting ‘average-high’ starting wellbeing, participants reporting ‘low’ starting wellbeing exhibited greater improvements (BCa 95% CI [−31.8, −26.5]), with 60.8% moving into the ‘average-high’ wellbeing category. GE can play an important role in facilitating wellbeing and can provide alternative pathways for health and social care practice. Public health commissioners should consider integrating such interventions for patients experiencing low wellbeing or associated comorbidities.

Abstract WP246: Characteristic of Ischemic Stroke Prior Taking Direct Oral Anticoagulant versus Warfarin Treatment: Results From the PASTA Registry

Background and Purpose: The characteristics of patients with stroke prior receiving direct oral anticoagulant (DOAC) have not been fully clarified. We planned to recruit patients prospectively and to investigate the characteristics and outcomes in stroke patients taking DOAC and warfarin treatment prior to the event. Methods: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke patients receiving OAC. Patient enrollment started in April 2016 at 25 tertiary centers across Japan. We compared clinical characteristics and discharge modified Rankin Scale (mRS) between DOAC-and warfarin-treatment in patients with atrial fibrillation (AF). Results: A total of 580 patients (231 women; median age 80 [quartiles 73-84] years) were analyzed (Fig. A). Of these, 365 patients (63%) received prior DOAC treatment and the remaining 215 (37%) received prior warfarin treatment (Fig. B and C). There were significant differences in clinical characteristics and outcome between DOAC-and warfarin-treatment prior to the event regarding initial NIHSS score (median [quartiles]: DOAC, 4 [2-16] vs. warfarin, 9 [3-21]; P =0.0001), rate of medium-large size of infarct (DOAC, 202/340 [59%] versus warfarin, 152/203 [75%]; P =0.0003) and the proportion of patients with favorable outcome (mRS, 0-3: DOAC 218/354 [62%] vs. warfarin 108/212 [49%]; P =0.0036). Subclassification according to DOAC dosing revealed patients with low-dose (259/365; 71%) to be older and to have a higher NIHSS score compared with regular dose (low-dose, 5 [2-17] vs. regular-dose, 3 [1-11]; P =0.0023) (Fig. D). Type of DOAC agent did not result in relevant differences in clinical characteristics or outcome (Fig. E). Conclusions: Our results showed that patients with DOAC treatment before the event showed smaller infarct size, milder initial stroke severity, and favorable outcome compared to patients with warfarin.

Abstract WP72: Low kV Computed Tomography Cerebral Angiogram Using Third-Generation Reconstruction Algorithm Provides Significantly Improved Image Quality With Lower Contrast and Radiation Exposure

Introduction/Aim: We aimed to determine if CTA imaging using third generation reconstruction algorithm and lower contrast dose-low kVp technique (LD-CTA) was comparable to regular contrast dose CTA at 120 kVp using a sinogram affirmed iterative reconstruction algorithm (ND-CTA). Methods: Retrospective imaging review of 100 consecutive patients (50 each in LD- and ND-CTA groups). Two readers independently assessed the subjective image quality across multiple vascular segments on a Likert-like scale. Contrast- and signal-to-noise ratios (CNR/ SNR) were compared for the mid-M1-MCA vessels bilaterally and the mid-basilar artery. Fisher’s exact test was used to compare subjective image quality. Interclass correlation coefficient (ICC) was calculated for the SNR/CNR values. Finally differences in contrast dose, CT-dose index (CTDI) and dose length product (DLP) were compared using Mann-Whitney U test. Results: Both observers showed excellent correlation in subjective image quality (mean percentage agreement of 95.2% (84-100%) for group-1 versus 89.2% (82%-98%) for group-2). The subjective scores were not statistically different in the anterior circulation but showed significantly better image quality for the basilar artery. LD-CTA group showed significantly better SNR and CNR (p &lt; 0.0001) for both MCA vessels and the basilar artery. ICC showed moderate correlation (0.51-0.63) between the observers. Student paired t-test did not show any significant difference between the observers. LD-CTA group also used lower contrast (49 cc versus 103 cc in ND-CTA) and had lower radiation exposure (DLP/ CTDI for both groups 268.3/12.42 vs 519.5/ 25.15, both &lt; 0.0001). Conclusion: Next-generation reconstruction algorithm and low-Kv scanning significantly improved image quality on cerebral CTA images despite lower contrast dose, and in addition, have lower radiation exposure.

Contribution of Regional anaesthesia on health economics: cost effectiveness of preemptive TAP block in Laparoscopic cholecystectomy

Objective: Regional anaesthesia can play a vital role as a supplement of general anaesthesia inlaparoscopic cholecystectomy surgery. In this study we postulated that preemptive bilateral dualtransversus abdominis plane (BD - TAP) block has the potential to reduce the requirement of volatileanaesthetic, muscle relaxant, postoperative opioid demand and shortening of hospital stay in laparoscopiccholecystectomy surgery, ultimately total cost. Method: Total 40 patients ASA I - II undergoing laparoscopic cholecystectomy surgery were randomlyassigned into two equal groups of 20 patients each. All patients received preemptive IV Paracetamol (15mg/kg), IV Diclofenac (1 mg/kg) and BD - TAP block. Block was performed with bilateral Subcostal(medial to linea semilunaris) and lateral TAP injection with total 70 ml drug volume. Group A receiveda drug solution containing plain Bupivacaine 15 ml (0.1%), Lidocaine 35ml (1%), Dexamethasone 10mg. Group B received a total 70 ml normal saline injection. Maintenance of anaesthesia was accomplishedwith low flow anaesthesia (0.5 - 1.0 L/min) accompanied by BIS monitoring, maintaining BIS index 45- 55. All patients received Sevoflurane with N2O 60%. Muscle relaxation was guided by TOF monitoringand supplemental dose was adjusted by the TOF counting. Postoperative analgesia was maintainedwith IM pethidine in p.r.n dose and oral paracetamol in regular doses. Total opioid requirement, musclerelaxant and volatile anaesthetic used and duration of postoperative hospital stay were recorded. Result: BD - TAP block reduced the Sevoflurane requirement, group A 5.5 (± 0.05) ml/ hr and group B6.8 (± 0.9) ml/ hr (p &lt; 0.05). It also reduced the requirement of Rocuronium in comparison to controlgroup, group A 49.5 (± 2.85) mg and in group B 58 (± 4.21) mg (p &lt; 0.05). Postoperative pethidinerequirement, group A 135 (± 22.9) mg and group B 375 (± 46) mg (p &lt; 0.05). It also facilitated rapidhospital discharge, group A 1.16 (± 0.5) days and group B 2.03 (± 0.5) days (p &lt; 0.05). Conclusion: In this study it is demonstrated that preemptive (BD - TAP) block in laparoscopiccholecystectomy surgery is associated with reduced requirement of volatile anaesthetic, muscle relaxantand postoperative opioid consumption. It seems that regional anaesthesia has a big contribution inmodern health economics and national health policy should consider this issue. JBSA 2020; 33(1): 3-9

P823 DNA methylation profiles accurately predict vedolizumab response and remain stable during induction and maintenance treatment in Crohn’s disease

Abstract Background While the use of biologicals has revolutionised the treatment of Crohn’s disease (CD) in recent decades, many patients fail to respond or lose response over time. Predictors for treatment selection and/or success are lacking. Vedolizumab (VDZ) induces corticosteroid-free clinical remission in 29% and endoscopic remission in 36% of patients after 6 months. Accumulating evidence suggests that the epigenome, mainly DNA-methylation, is associated with certain CD phenotypes. Here, we investigated whether the DNA methylome of peripheral blood (PB) obtained from CD patients treated with VDZ was associated with clinical and endoscopic response or non-response to treatment. Methods We prospectively recruited CD patients scheduled to start VDZ treatment at regular dosage and who underwent baseline endoscopy. PB was collected prior to treatment (T1) and at a median of 14 weeks (T2) into treatment. Additionally, a third PB sample was collected after a median of 79 weeks (T3) into treatment for 10 CD patients. DNA methylation was measured using the Illumina Infinium Methylation EPIC BeadChip. After a median 27 weeks of treatment, patients were characterised as responders (R) or non-responders (NR) based on endoscopic changes (R= ≥50% reduction in SES-CD score) combined with either steroid-free clinical remission (≥3 point drop in HBI, no systemic steroids) and/or biochemical response (≥50% reduction in C-reactive protein and faecal calprotectin). Results We analysed data of 16 R and 14 NR patients, 53% of which were female with a median age of 37. No significant differences in age, sex or smoking were observed between R and NR. All patients had measurable serum VDZ concentration at the second endoscopy. To identify response-associated biomarkers, we performed elastic net regression through repeated cross-validation. We identified 38 differentially methylated probes (DMPs) associated with response (Figure a), 7 of which were located in gene promoters. Performance-wise the DMPs displayed a sensitivity of 0.86 and a specificity of 0.8 in predicting response (Figure b). Notably, the degree of methylation for the response-associated DMPs did not change after 14 weeks of treatment (n = 30), or even after 79 weeks (n = 10). Conclusion Here, we show that the DNA methylome in peripheral blood is associated with response to VDZ. As the difference in methylation remained stable during induction and maintenance treatment with VDZ, inflammation did not appear to affect the response-associated DMPs. Our observations provide evidence towards the establishment of epigenetic marks with predictive biomarker capabilities, paving the road towards personalised treatment selection in CD.

Case report: Successful induction of buprenorphine/naloxone using a microdosing schedule and assertive outreach

BackgroundThe requirement for moderate withdrawal prior to initiation can be a barrier to buprenorphine/naloxone induction.Case presentationWe aimed to use a microdosing regimen to initiate regular dosing of buprenorphine/naloxone in a high-risk patient with a history of failed initiations due, in part, to withdrawal symptoms. Using an assertive outreach model and a buprenorphine/naloxone microdosing schedule, we initiated treatment of an individual’s opioid use disorder. There was a successful buprenorphine/naloxone microdosing induction as the team reached a therapeutic dose of buprenorphine/naloxone. Including the induction period, the medication was used consistently for 4 weeks.ConclusionsA microdosing schedule can be used to induce a patient onto buprenorphine/naloxone with no apparent withdrawal; gradually reducing illicit substance use. This case report builds on previous literature, highlighting ways to minimize barriers to induction of buprenorphine/naloxone, using a microdosing schedule and assertive outreach. Given the safety profile of buprenorphine and its potential to be a lifesaving intervention, a larger study of microdosing is indicated.

The Minimal Clinically Relevant Change of the FOG Score.

Freezing of gait is a highly disabling symptom in persons with Parkinson's disease (PwP). Despite its episodic character, freezing can be reliably evaluated using the FOG score. The description of the minimal clinically relevant change is a requirement for a meaningful interpretation of its results. To determine the minimal clinically relevant change of the FOG score. We evaluated video recordings of a standardized freezing-evoking gait parkour, i.e., the FOG score just before and 30 minutes after the intake of a regular levodopa dose in a randomized blinded fashion. The minimal clinically relevant response was considered a value of one or more on a 7-step Likert-type response scale [-3; +3] that served as the anchor. The minimal clinically relevant change was determined by ROC analysis. 37 PwP (Hoehn & Yahr stages 2.5-4, 27 male, 10 female) were aged 68.2 years on average (range 45-80). Mean disease duration was 12.9 years (2-29 years). Minimum FOG score was 0 and Maximum FOG score was 29. Mean FOG scores before medication were 10.6, and 11.1 after medication intake, with changes ranging from -14.7 to +16.7. The minimal clinically relevant change (MCRC) for improvement based on expert clinician rating was three scale points with a sensitivity of 0.67 and a specificity of 0.96. The FOG score is recognized as a useful clinical instrument for the evaluation of freezing in the clinical setting. Knowledge of the MCRC should help to define responses to interventions that are discernible and meaningful to the expert physician and to the patient.

An observational case-control study comparing the recovery profile in patients receiving additional dose of anticonvulsant vs. regular dose during supratentorial craniotomy.

Background and Aims:Anticonvulsants are used routinely for seizure prophylaxis in patients with supratentorial tumour who present with/without seizures. Excessive use of prophylactic anticonvulsant may delay the recovery from anaesthesia. We have studied the recovery profiles of patients who received an additional dose of anticonvulsant in comparison with those who received only the regular dose.Methods:In this prospective observational study, patients were anaesthetised using standard anaesthesia protocol. An additional dose of anticonvulsant was administered in one group, while the other group received only the regular dose. Time taken for extubation, eye opening, obeying commands and orientation were compared between the two groups. Haemodynamics, depth of anaesthesia, the plasma anticonvulsant levels and the incidence of seizures were compared between the two groups.Results:A total of 36 patients were studied, of which 19 received regular dose and 17 received an additional dose. There was no significant difference in recovery time between the two groups. Subgroup analysis was performed for phenytoin and sodium valproate. There was a clinically significant delay in recovery in patients who received an additional phenytoin compared to those who received regular dose (time to obey commands >15 min and orientation time >1hour) but, it was not statistically significant. Administration of an additional dose of valproate did not prolong the recovery time.Conclusion:An additional dose of sodium valproate did not cause a delay in recovery both, clinically and statistically. However, the administration of an additional dose of phenytoin caused a clinically significant delay in recovery but was not statistically significant.