Mean Percentage Reduction Research Articles

Abstract 4134364: Predicted Low-Density Lipoprotein Cholesterol and Cardiovascular Outcomes Lowering With Inclisiran in Patients With or Without stroke: Insights from SIRIUS in silico trial.

Introduction: Inclisiran, an siRNA, targeting PCSK9 mRNA, reduces LDL-c levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower cardiovascular (CV) events in virtual patients with atherosclerotic cardiovascular disease (ASCVD). Research question: This analysis predicted the potential efficacy of inclisiran on CV outcomes in virtual patients with or without prior ischemic stroke (IS). Methods: The SIRIUS trial was conducted using a calibrated and validated knowledge-based mechanistic computational model of ASCVD applied to a virtual population with LDL-C ≥ 70 mg/dL. Each virtual patient was its own control. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statin with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal IS over 5 years in patients with or without prior IS. Occurrence of fatal and non-fatal (IS) was also individually assessed in time-to-first-event analyses. Results: Among 204,691 virtual SIRIUS ASCVD patients, 39 371 (19%) had prior IS. At 5 years, the predicted mean percentage reduction in LDL-C with inclisiran as compared to placebo was –49.17% and –49.88% in patients with or without prior IS respectively. Patients with prior IS were at higher risk of 3P-MACE than patients without IS both with placebo and inclisiran (17.01% vs 14.41% with placebo and 13.44% vs 10.83% with inclisiran). However, the predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm for both prior IS and no prior IS (HR 0.78 medium uncertainty and 0.74 low uncertainty respectively). Compared to placebo, inclisiran was also predicted to consistently reduce fatal and non-fatal IS in patients with or without prior IS (5.45% vs 7.22%; HR: 0.75 medium uncertainty and 1.87% vs 2.54%; HR: 0.73 medium uncertainty respectively). Conclusion: SIRIUS provides insights into the potential efficacy of inclisiran on CV events suggesting a substantial 3P-MACE and fatal and non-fatal IS reduction in ASCVD patients including those with prior IS, several years before the availability of results from ongoing outcomes trials (ORION-4, VICTORION-2P).

Three-Dimensional Planimetry Assessment of Dental Plaque-Covered Area Reduction after Rinsing with 0.2% Sodium Hypochlorite Solution as Part of a Guided Biofilm Therapy® Protocol-Pilot Longitudinal Study.

Background/Objectives: Less often employed as a rinsing solution for controlling oral biofilms, NaOCL was used in oral rinses at various concentrations in steps 1 and 4 of periodontal therapy. The aim of this study was to quantitatively evaluate the biofilm-disruptive properties of a 0.2% NaOCl solution in standardized oral rinses using dedicated plaque-disclosing agents and 3D scanning methods in patients undergoing the regular Guided Biofilm Therapy® protocol. Methods: Eight patients with at least 20 teeth present evenly distributed between the two arches were included. After 24 h of refraining from oral hygiene, dental arches were stained with a disclosing agent, the subjects rinsed for 20 s, clinical photographs and 3D scans were performed, subjects rinsed again for 20 s, photographs and 3D scans were performed again, and then the GBT® protocol was resumed as usual. Data representing areas covered with dental plaque were acquired using the "Medit Scan for Clinics" software and then underwent a post-processing and rendering process. The outcome variable was the percent reduction in the plaque-covered areas. Results: For the upper jaw, the estimated mean percent reduction in the biofilm-covered area was 39.65%, while for the mandible, it was 38.26%. The analysis of individual photographs revealed changes in the plaque-covered areas and reductions in the color intensity of the residual plaque-covered areas under identical lighting conditions. Conclusions: When analyzed using 3D intraoral scanning, the 0.2% NaOCl rinsing solution seems to be a clinically efficient disruptor/dissolvent of the oral biofilm, both when integrated into modern protocols of periodontal therapy like GBT® and for home self-care.

A Descriptive, PostHoc Analysis of Efficacy and Safety of Risankizumab in Diverse Racial and Ethnic Patient Populations With Moderate-to-Severe Psoriasis.

Historically, patients with skin of color are underdiagnosed with psoriasis and underrepresented in clinical trials. In this study, we assess the efficacy and safety of risankizumab in patients with moderate-to-severe plaque psoriasis by race and ethnicity in the open label extension LIMMitless (NCT03047395). Patients received continuous treatment with 150mg risankizumab through their initial trial and the open label extension. Patients self-identified their race and ethnicity. Efficacy was assessed using Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety is reported by events/100 patient-years. A total of 897 patients (race: 662 White, 196 Asian, 25 Black or African American, 14 Other; ethnicity: 98 Hispanic or Latino, 799 non-Hispanic or Latino) were included in this analysis. Compared to baseline, patients had a mean percent reduction in PASI between 94.6% (Asian) and 99.3% (Black or African American) and reported mean percent improvements in DLQI ranging from 87.1% (Asian and Black or African American) to 93.7% (Hispanic or Latino) at week 100. While the data presented here comprise a small retrospective descriptive analysis and cannot detect statistical differences, efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis appears similar across the racial and ethnic groups studied and no new safety signals were detected.

Efficiency of Neoseiulus californicus (McGregor) (Acari: Phytoseiidae) for controlling three plant-feeding mites on guava trees in Egypt

ABSTRACT Tegolophus guavae (Boczek), Brevipalpus phoenicis (Geijskes), and Tetranychus urticae Koch are plant-feeding mite pests that cause severe damage to the foliage and fruits of guava trees in Egypt. The phytoseiid mite, Neoseiulus californicus (McGregor), was released at three densities (100, 200, and 300 predators/tree). The results indicated that the efficiency of N. californicus was significantly influenced by the release rate. The highest mean reduction percentage after six months of release for T. guavae, B. phoenicis, and T. urticae was, respectively, at 300 predators/tree (64.90, 81.15, and 81.11%) in 2021 and (74.89, 83.76, and 83.07%) in 2022. The mean fruit yields (kg/treatment) in the released plots were substantially greater than those in the control (ranging from 8–16%). The current result suggests that releasing N. californicus is a viable option for biological guava mite pest management.

Silencing siRNA microneedle patches versus silicone sheets in reducing post-surgical scars: a randomized single-blinded intra-individually controlled clinical trial.

A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars. We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets. This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60. At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%). There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.

Magnetic Resonance Imaging Guided Radiation Therapy for Splenomegaly: Clinical Experiences and Technical Tips

IntroductionSplenomegaly is a common manifestation in chronic lymphoid and myeloid malignancies. While splenectomy is the preferred treatment for symptomatic splenomegaly, it carries significant risks. Radiotherapy (RT) has traditionally been considered a palliative option. This study explores the use of Magnetic Resonance-Guided Radiotherapy (MRgRT) for splenic irradiation (SI) in patients with myelofibrosis (MFI) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). MethodsThis single-center retrospective analysis includes patients with MFI and MDS/MPN who underwent MRgRT SI between 2018 and 2022. Ten 1 Gy fractions were delivered to the PTV (spleen+3/5mm margin). An adaptive online/offline strategy has been used to reduce the dose to healthy organs. Dosimetric data and clinical outcomes, including pain relief, gastrointestinal symptoms, and hematological values, were assessed. ResultsTwelve patients completed SI without interruption, with supportive transfusions as needed for cytopenias. Pain and gastrointestinal symptoms relief was observed in most cases. The mean percentage reduction in spleen volume was 53.61%, with an average cranio-caudal extension reduction of 77.78%. Twenty-nine (24.2%) out of 120 fractions were online adapted and 14 (11.7%) were replanned offline. Non-hematological toxicities were not reported. At a median follow-up of 12.9 months, 6 patients died, while 9 patients underwent hematopoietic cell transplantation, with 6 of them surviving. ConclusionThis study demonstrates MRgRT SI feasibility in MFI and MDS/MPN patients, offering symptom relief and significant spleen volume reduction. Real-time setup verification and adaptive planning allowed for tailored treatment with reduced margins, minimizing healthy tissue exposure. Larger prospective studies with longer follow-up are needed to further validate its efficacy and safety.

A UK multicentre audit of the management of patients with primary hypercholesterolaemia or mixed dyslipidaemia with bempedoic acid against published lipid-lowering treatment targets.

Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, was introduced to UK practice via a pre-reimbursement access scheme for adults with primary hypercholesterolaemia or mixed dyslipidaemia who are at high risk of cardiovascular disease, in whom statins are either not tolerated or contraindicated, who have not achieved target cholesterol, despite being on ezetimibe therapy, and do not qualify for PCSK9 inhibitor treatment. This retrospective multicentre audit aimed to evaluate the achievement of lipid-lowering targets with bempedoic acid in UK patients based on recommendations in the Joint British Societies (JBS) guidelines for the prevention of cardiovascular disease. Pseudo-anonymized medical record data for 221 adults treated with bempedoic acid as part of the UK scheme were entered into a bespoke data collection tool at four UK hospitals. Patient demographics, clinical characteristics, treatment pathways and lipid assessment results (against JBS lipid-lowering targets) were collected against pre-specified criteria. Overall, 54% (99/184) of patients achieved the JBS2 audit standard (total cholesterol (TC) <5 mmol/L and low-density lipoprotein cholesterol (LDL-C) <3 mmol/L or ≥25% reduction in TC and ≥30% reduction in LDL-C) at 12 weeks post-initiation. At week 12, the mean absolute change in LDL-C was -1.0 mmol/L; the mean percentage reduction from baseline was 22.0%. Additionally, 52% (96/185) of patients had an LDL-C of <3 mmol/L and 10% (18/185) an LDL-C of <1.8 mmol/L at 12 weeks (as per JBS3). This audit highlights the role of bempedoic acid as part of combination therapy for a population with previously limited treatment options.

Neoadjuvant chemotherapy for advanced eyelid and periocular sebaceous gland carcinoma: a study of 25 cases.

To report the outcomes of platinum-based neoadjuvant chemotherapy (NACT) for eyelid and periocular sebaceous gland carcinoma (eSGC). Retrospective study of 25 patients. The mean age at presentation of eSGC was 59years. The mean tumor basal diameter was 46mm. By the 8th edition of AJCC classification, tumors belonged T2 (n = 2, 8%), T3 (n = 6, 24%), and T4 (n = 17, 68%); N1 (n = 12,48%); and M1 (n = 1, 4%). NACT with 5-fluorouracil (5-FU) and cisplatin/carboplatin was administered in 21 (84%)/4 (16%) patients, respectively. The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 2 (median, 3). The mean percentage reduction of tumor basal volume after neoadjuvant chemotherapy was 65% (median, 60%). After NACT, 12 (48%) patients underwent surgical treatment, 6 (12%) patients underwent EBRT, and 4 (8%) underwent adjuvant chemotherapy. A total of 11 (44%) patients were lost to follow-up during the course of treatment, of whom 3 died from metastatic disease. In 16 patients followed up for ≥ 3months, complete tumor control was achieved in 11 (69%) patients, local tumor control in 14 (88%), and globe salvage in 7 (44%) at a mean follow-up of 25months (median, 7months; range, 3 to 110months). No tumor recurrence was seen in any case. One (4%) serious adverse event of cardiotoxicity was noted. Platinum-based NACT is a suitable option for eSGC with advanced tumors and locoregional metastasis. Adverse events are rare and in patients compliant with treatment, NACT-based combination therapy offers globe salvage and systemic tumor control.

Dupilumab treatment in paediatric atopic dermatitis (2 to 18 years): Spanish multicentre retrospective real-life study.

Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.

A novel chlorin derivative Shengtaibufen (STBF) mediated photodynamic therapy combined with iodophor for the treatment of chronic superficial leg wounds infected with methicillin-resistant Staphylococcus aureus: A retrospective clinical study

ObjectiveChronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers. Patients and methodsThis was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm2) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded. ResultsWe found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm2 to 6.59±7.94 cm2) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm2 to 13.43±9.32 cm2) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 107±2.69 × 107 to 8.94 × 104±1.92 × 105 CFU/cm2, p<0.0001) in the STBF-PDT+iodophor group and 1.82% (from 6.61 × 107±2.13 × 107 to 6.49 × 107±2.01 × 107 CFU/cm2, p=0.029) in the control+iodophor group. The wound-QoL in STBF-PDT+iodophor group had a 51.62% decrease in overall score (from 29.65±9.33 at the initial to 14.34±5.17 at week 8, p<0.0001) compared to those receiving red light and routine wound care (from 30.73±17.16 to 29.32±15.89 at week 8, p=0.003). Moreover, patients undergoing STBF-PDT+iodophor exhibited great improvements in all domains of wound-QoL (physical, psychological and everyday-life), whereas the control+iodophor group ameliorated in only one field (everyday-life). ConclusionOur data confirmed that a novel photosensitizer, STBF-mediated PDT, when combined with iodophor, served as a potential modality for MRSA infection and a possible therapy for other drug-resistant microorganisms, and as a promising alternative for chronic cutaneous infectious diseases.

Bactericidal Effect of Different Photochemical-Based Therapy Options on Implant Surfaces-An In Vitro Study.

Objectives: Photochemical systems are frequently recommended as an adjuvant treatment option in peri-implantitis therapy. The aim of the present study was to evaluate the efficacy of these treatment options, as well as a novel curcumin-based option, in a biofilm model on implants. Methods: Eighty dental implants were inoculated with an artificial biofilm of periodontal pathogens and placed in peri-implant pocket models. The following groups were analyzed: I, photodynamic therapy (PDT); II, PDT dye; III, curcumin/DMSO + laser; IV, curcumin/DMSO only; V, dimethyl sulfoxide (DMSO) only; VI, photothermal therapy (PTT); VII, PTT dye; VIII, control. After treatment, remaining bacterial loads were assessed microbiologically using quantitative real-time polymerase chain reaction analysis. Results: The PDT, PTT, and DMSO treatment methods were associated with statistically significant (p < 0.05) improvements in germ reduction in comparison with the other methods and the untreated control group. The mean percentage reductions were as follows: I (PDT) 93.9%, II (PDT dye) 62.9%, III (curcumin/DMSO + laser) 74.8%, IV (curcumin/DMSO only) 67.9%, V (DMSO) 89.4%, VI (PTT) 86.8%, and VII (PTT dye) 66.3%. Conclusions: The commercially available PDT and PTT adjuvant treatment systems were associated with the largest statistically significant reduction in periopathogenic bacteria on implant surfaces. However, activation with laser light at a suitable wavelength is necessary to achieve the bactericidal effects. The use of curcumin as a photosensitizer for 445 nm laser irradiation did not lead to any improvement in antibacterial efficacy in comparison with rinsing with DMSO solution alone.

Unmasking Acne: Azithromycin Edges Out Doxycycline in Randomized Trial at Tertiary Care Centre

Background: Acne vulgaris, a prevalent global condition, often necessitates antibiotic therapy. Doxycycline has been a mainstay treatment; however, recent research suggests azithromycin might be superior. Conflicting data and a lack of local studies regarding their comparative efficacy warrant further investigation. Objectives: This study aimed to compare the efficacy of oral azithromycin with oral doxycycline in treating acne vulgaris at a tertiary care hospital in Islamabad. Methods: A randomized controlled trial was conducted. Patients aged 14-30 years (n=190) were enrolled and randomly assigned to either azithromycin or doxycycline treatment groups. Baseline and post-treatment (12 weeks) Global Acne Grading System (GAGS) scores were assessed. Percent reductions in GAGS score were categorized into four groups (&lt;25%, 25-50%, 51-75%, and &gt;75%) for intergroup comparison. Written informed consent was obtained from all participants. Results: The mean patient age was 21.30±4.93 years, with a female predominance (male:female ratio 1:1.2). Most patients had Fitz-Patrick Skin Type-V (64.7%) compared to Type-IV (35.3%). Baseline GAGS scores were comparable between groups (p=0.612). Notably, post-treatment GAGS scores were significantly lower in the azithromycin group (p&lt;0.001), demonstrated by a greater mean change (19.33±3.03 vs. 17.70±2.99; p&lt;0.001) and percent reduction (81.87±8.74 vs. 75.97±11.12%; p&lt;0.001) compared to doxycycline. Additionally, 75.3% of patients achieved an excellent reduction in GAGS score, with a significantly higher proportion observed in the azithromycin group (87.4% vs. 63.2%; p&lt;0.001). Similar significant differences were observed across subgroups based on age, gender, and skin type. Conclusion: This study suggests that azithromycin demonstrates superior efficacy to doxycycline for acne vulgaris management, regardless of patient demographics or skin type. Its established better safety profile further supports its potential as a preferred therapeutic option in future dermatological practice. Keywords: Acne Vulgaris, Azithromycin, Doxycycline, Percent Reduction in GAGS Score

Effectiveness and Safety of Upadacitinib for Adolescents with Atopic Dermatitis in a Real-World Setting.

The estimated prevalence of atopic dermatitis (AD) among adolescents (12-17years of age) is about 14.8%. AD compromises sleep quality and may be associated with poor scholastic performance, mood disruptions, low self-esteem, and difficulty in building social relationships. Upadacitinib was recently approved by the European Medicines Agency for the treatment of moderate-to-severe AD in patients aged ≥12years who are candidates for systemic treatment. The aim of this real-world study was to determine the effectiveness in disease control and safety of upadacitinib in adolescents aged 12-17yearswithmoderate-to-severe AD. This is a retrospective study in adolescents with moderate-to-severe AD treated with upadacitinib 15mg between July 2022 and February 2024 at six Italian dermatological referral centres. The primary endpoint was to analyse the evolution of the response in terms of absolute Eczema Area and Severity Index (EASI) value, as well as the percentage of patients achieving 75% and 90% improvement in EASI (EASI75 and EASI90) from baseline to weeks (W) 4, 16, 24, and 52. Secondary endpoints included the assessment of treatment efficacy in terms of Numerical Rating Scale (NRS) for pruritus (P-NRS) and sleep (S-NRS), Children's Dermatology Life Quality Index (c-DLQI), and safety. Thirty-six patients [males: 18 (50%)] were evaluated. A statistically significant improvement of EASI was observed at each timepoint, as stated by a mean percentage reduction from baseline of 72.2% at W4, 82.7% at W16, of 86.4% at W24 (n=34) and of 92.7% at W52 (n=18) (p<0.0001). At W4, 21/36 (58.3%) achieved EASI75 and 12/36 (33.3%) EASI90. At W16, 29/36 (80.5%) achieved EASI75 and 19/36 (52.8%) EASI90. At W24, 32/34 (94.1%) reached EASI75 and 24/34 (70.6%) EASI90. Finally, at W52 all the assessed patients (n=18) maintained EASI75 and 14/18 (77.7%) reached EASI90. Likewise, a statistically significant reduction of c-DLQI, P-NRS and S-NRS was observed at each timepoint. Our real-world experience seems to confirm the efficacy and safety of upadacitinib for the long-term treatment of moderate-to-severe AD in adolescents.

Effect of Brolucizumab and Aflibercept on the Maximum Thickness of Pigment Epithelial Detachments and Sub-Retinal Pigment Epithelium Fluid in HAWK and HARRIER

ObjectiveTo compare the efficacy of brolucizumab and aflibercept treatment in reducing maximum thickness of pigment epithelial detachments (PED) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration (nAMD) in the HAWK and HARRIER studies. DesignHAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies Subjects, participants, and/or controls1,775 patients across 11 countries were included in the HAWK study and 1,048 patients across 29 countries were included in the HARRIER study. Method and interventionsAfter three monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks (q12w) or q8w if disease activity (DA) was detected. Aflibercept-treated eyes received fixed q8w dosing. Main outcomes measuresMaximum thickness of PED and sub-RPE fluid across the macula were assessed at baseline through Week 96 in the brolucizumab- and aflibercept-treated patients, and in the patient subgroups with DA at Week 16 (matched in terms of injection number and treatment interval). ResultsAt Week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PED and sub-RPE fluid in brolucizumab-treated patients versus aflibercept-treated patients (PED: 19.7% [n=336] vs 11.9% [n=335] in HAWK; 29.5% [n=364] vs 18.3% [n=361] in HARRIER. Sub-RPE fluid: 75.4% vs 57.3% in HAWK; 86.0% vs 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at Week 16. ConclusionsThis analysis shows that brolucizumab achieved greater reductions in PED and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER.

Tratamiento de la hipertrigliceridemia grave mediante recambio plasmático terapéutico en pacientes con pancreatitis aguda o en riesgo de padecerla

Introduction and objectivesTPE drastically reduces serum triglyceride (sTG), but its role in the treatment of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) or at risk of developing it, is not well established. The objectives were to assess the effectiveness and safety of TPE in the treatment of severe HTG (sHTG), as well as to evaluate the severity of HTG-AP treated with TPE. Materials and methodsObservational-retrospective-single-center study, in which a descriptive analysis of sHTG treated with TPE was conducted, with the aim of treating HTG-AP or preventing its recurrence. TPE was performed if sTG≥ 1000 mg/dL after 24 hours of admission. Results42 TPE were performed to treat 35 sHTG in 23 patients: 29 HTG-AP, and 6 sHTG with previous HTG-AP. Among the patients, 37% (13/55) were women, with 37 ± 14 years-old, 74.3% had normal BMI (25/35), 34% (12/35) were drinking > 40 g/alcohol/day and 54% (19/35) were diabetics. TPE significantly reduced the baseline sTG (4425 ± 2782 mg/dL vs. 709 ± 353 mg/dL, p < 0.001) in a single session, achieving a mean percentage reduction of 79 ± 13%; 20% (7/35) of sHTG cases required two TPE sessions to reduce sTG to < 1000 mg/dL. Adverse effects were reported in 4/42 TPE sessions (9,5%). sHTG-AP was observed in 3% of cases (1/29), and there were no deaths. sTG at 24 hours of admission showed no relation with the severity of APs. ConclusionThe treatment of sHTG with TPE, with the aim of treating HTG-AP or preventing its recurrence, reduces sTG quickly and safety.

Effect of ultrasonic and Er,Cr:YSGG laser-activated irrigation protocol on dual-species root canal biofilm removal: An in vitro study.

The aim of the study was to investigate the disinfecting efficacy of a standardized irrigating solution activated by ultrasonics or laser irradiation on mature dual-species biofilms at different root levels in vitro. Conventional access cavity preparations were done on 160 single-rooted mandibular premolar teeth with single canals. Freshly extracted oral microbial strains of Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, and Candida albicans after biochemical confirmation were used to generate two discrete dual-species microbial inoculums. The sterilized tooth samples were randomly segregated into two groups (n = 80) and inoculated with a mixed inoculum of S. aureus + E. faecalis strains (Group 1) and S. mutans + C. albicans strains (Group 2), respectively. Following the 21-day incubation period under aerobic conditions, the infected specimens in each group were divided into four subgroups (n = 20) and subjected to experimental treatment protocols. This included a positive control (no treatment of biofilms), syringe irrigation alone with TruNatomy needle, passive ultrasonically activated irrigation with 20# Irrisafe tip, and laser agitation of irrigant with Er,Cr:YSGG laser using RFT 2 laser tip. Root canals of experimental specimens (except the control samples) are instrumented with TruNatomy rotary file system using 1:1 mixture of 3% NaOCl and 18% etidronic acid as irrigants. The quantitative assessment of reduction in viable biofilm microbes after treatment was done using colony-forming unit counts and confocal laser scanning microscopy image analysis. The obtained data were analyzed statistically with a significant level set at 0.05. Laser-assisted irrigation has shown a considerably higher mean percentage reduction of microbes compared to ultrasonic agitation and the syringe irrigation showed the least microbial reduction (P = 0.001). No significant difference was noted between the three root regions of ultrasonic and laser groups (P > 0.05), whereas in the syringe groups, apical portions showed higher microbial counts compared to cervical and mid-root regions (P = 0.001). Erbium laser-assisted irrigation has performed superior to ultrasonic agitation against both the experimental dual-species biofilms, while the syringe irrigation showed the least microbial reduction specifically at apical root portions.

#636 A phase 4, open label, multicenter prospective study of the safety and efficacy of agalsidase beta in Chinese patients with Fabry disease

Abstract Background and Aims Fabry disease (FD) is a rare inherited lysosomal storage disease caused by pathogenic GLA gene variants which result in a deficiency of the enzymatic activity of α-galactosidase A. Enzyme replacement therapy (ERT) is the mainstay of FD-specific treatment, but there are currently no reported clinical trials of ERT for FD in the Chinese population. This is the first phase 4 study to evaluate the safety and efficacy of ERT for FD in China since the approval of agalsidase beta in China in 2019. Method A 54-week, phase 4, open label, single arm, prospective, post-marketing surveillance (PMS) study of agalsidase beta (NCT05054387) was performed at 6 sites in China. Twenty-two Chinese ERT-naïve FD participants (≥8 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 were enrolled and received infusions of agalsidase beta (Fabrazyme®, Sanofi) at a dose of 1.0 mg/kg every 2 weeks for up to 48 weeks. The primary endpoint was safety and tolerability of agalsidase beta. The endpoints of clinical efficacy included the changes of plasma globotriaosylceramide (GL-3), globotriaosylsphingosine (Lyso-GL-3), FD symptoms (including angiokeratoma, hypohidrosis, anhidrosis, abdominal pain, headache, tinnitus, heat tolerance, and activity tolerance), and eGFR from baseline to week 48. A post-hoc subgroup analysis was conducted to explore the differences in ERT efficacy between two subgroups of different ages (&amp;lt;30 years and ≥30 years). Results All 22 patients completed the study intervention. There were 18 males (81.8%) and the mean age of ERT initiation was 29.0 ± 13.5 years. Treatment-related adverse events (AEs) and infusion-associated reactions (IARs) were reported in 8 participants (36.4%), which was less than ∼60% as previously reported for IARs. Most AEs were mild or moderate and no AE caused permanent treatment discontinuation or death. The mean plasma GL-3 and Lyso-GL-3 levels decreased remarkably at week 6 and remained stable throughout the trial, with the mean percentage reduction from baseline to week 6 through week 48 ranged from −34.6% ± 27.4% to ­41.9% ± 14.9% and −58.8% ± 20.2% to ­64.9% ± 12.7%, respectively (Fig. 1a and b). The reduction was more remarkable for the classic male patients (n = 18; GL-3: 7.99 ± 2.19 ug/mL at baseline and 4.31 ± 1.71 ug/mL at week 48, −46.0% ± 18.4%; Lyso-GL-3: 83.11 ± 25.69 ng/mL at baseline and 25.89 ± 13.43 ng/mL at week 48, −67.8% ± 17.6%). Thirteen (59.1%) participants experienced improved FD symptoms at week 48, with no cases of worsening symptoms. The mean eGFR was 115.6 ± 37.3 mL/min/1.73 m2 at baseline and 118.4 ± 42.9 mL/min/1.73 m2 at week 48, with a change of 0.0 ± 12.4 mL/min/1.73 m2 from baseline to week 48 (Fig. 1c). In the subgroup analysis, participants were divided into the younger group with age &amp;lt;30 years (n = 11) and the older group with age ≥30 years (n = 11) according to their age of ERT initiation. At week 48, the reduction of mean plasma GL-3 (−47.1% ± 23.6% vs −22.0% ± 26.0%) and Lyso-GL-3 levels (−72.4 ± 17.3% vs −48.2% ± 19.8%), the stabilization of renal function (the mean change of eGFR from baseline to week 48: 5.2 ± 7.9 mL/min/1.73 m2 vs −5.2 ± 14.1 mL/min/1.73 m2) and the percentage of symptom improvement (81.8% vs. 36.4%) were generally more remarkable in the younger group than in the older group (Table 1). Conclusion This first phase 4 study of ERT for Fabry disease in China demonstrates that agalsidase beta is safe and well tolerated with a relatively low IAR rate, and effective in reducing plasma GL-3 and Lyso-GL-3, improving symptoms, and stabilizing renal function in Chinese patients with FD. Furthermore, the present study implies that patients who initiate ERT at a younger age benefit more from the therapy. Funding: Commercial support - Sanofi Pharmaceuticals.

#367 PROTECT and NefIgArd two-year proteinuria and eGFR outcomes in adults with IgA nephropathy: matching-adjusted indirect comparison

Abstract Background and Aims Immunoglobulin A (IgA) nephropathy is a rare kidney disorder characterized by deposition of IgA in the glomeruli causing progressive loss of kidney function and increased risk of kidney failure. In the absence of a head-to-head trial, this study used unanchored matching-adjusted indirect comparison (MAIC) of clinical trial data to compare two-year efficacy outcomes between Sparsentan in PROTECT and targeted-release formulation (TRF) budesonide plus real-world optimized and stable renin-angiotensin system inhibition (RASi) standard-of-care (SoC) in NefIgArd. Method We conducted an unanchored MAIC using individual patient level data from the PROTECT trial and aggregate data from the NefIgArd trial. Patients in the sparsentan arm of PROTECT were weighted to match key baseline characteristics of patients in the targeted-release formulation (TRF) budesonide + RASi SoC arm of NefIgArd based on publicly accessible, clinically pertinent baseline characteristics and prognostic factors using the method of moments. After weighting, percentage reduction of urine protein-creatinine ratio (UPCR) relative to baseline and two-year eGFR total slope (based on available data, chronic slope estimates are currently not available from NefIgArd) were estimated. A mixed model for repeated measures (MMRM) was used for UPCR relative percentage reduction and a random effect coefficient model for eGFR total slope. A two-tailed z-test with a pooled standard error was conducted for the indirect comparison. Results After assessing PROTECT and NefIgArd cross-trial characteristics on key outcome definitions, inclusion and exclusion criteria, and patient population, the two trials were considered sufficiently similar for unanchored MAIC. After weighting individual patient data from PROTECT, all matched baseline patient characteristics were well-balanced between arms of the two trials. Comparative results showed patients treated with sparsentan in PROTECT (−43.2% relative reduction in UPCR) exhibited a greater mean percentage reduction in proteinuria at two-years compared to TRF budesonide + RASi SoC (−30.7% relative reduction in UPCR), a relative percentage reduction of 18.1% (p = 0.03; Fig. 1A). For eGFR total slope, patients treated with sparsentan exhibited a slower decline in kidney function compared to TRF budesonide + RASi SoC, a difference of 0.54 ml/min/1.73 m2 per year; however, this difference was not statistically significant (p = 0.35; Fig. 1B). Conclusion Aligned to an earlier analysis of percentage reduction in proteinuria at 9-months (−37%, p &amp;lt; 0.0001 favoring sparsentan), our MAIC results show that sparsentan in PROTECT was associated with a greater relative percentage reduction in proteinuria at two-years compared to TRF budesonide plus real-world optimized and stable RASi SoC in NefIgArd. eGFR total slope for sparsentan in PROTECT was comparable to that reported for TRF budesonide plus real-world optimized and stable RASi SoC in NefIgArd. Results comparing chronic slope may provide a better indication of the long-term nephroprotective value of both therapies.

Impaired sleep-dependent memory consolidation predicted by reduced sleep spindles in Rolandic epilepsy.

Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in Rolandic epilepsy and related sleep-activated epileptic encephalopathies. We investigate the relationship between sleep spindle deficits and deficient sleep dependent memory consolidation in children with Rolandic epilepsy. In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using a validated automated detector. Twenty-three children with Rolandic epilepsy (14 with resolved disease), and 19 age- and sex-matched controls were enrolled. Children with active Rolandic epilepsy had decreased memory consolidation compared to control children (p=0.001, mean percentage reduction: 25.7%, 95% CI [10.3, 41.2]%) and compared to children with resolved Rolandic epilepsy (p=0.007, mean percentage reduction: 21.9%, 95% CI [6.2, 37.6]%). Children with active Rolandic epilepsy had decreased sleep spindle rates in the centrotemporal region compared to controls (p=0.008, mean decrease 2.5 spindles/min, 95% CI [0.7, 4.4] spindles/min). Spindle rate positively predicted sleep-dependent memory consolidation (p=0.004, mean MST improvement of 3.9%, 95% CI [1.3, 6.4]%, for each unit increase in spindles per minute). Children with Rolandic epilepsy have a sleep spindle deficit during the active period of disease which predicts deficits in sleep dependent memory consolidation. This finding provides a mechanism and noninvasive biomarker to aid diagnosis and therapeutic discovery for cognitive dysfunction in Rolandic epilepsy and related sleep activated epilepsy syndromes.

Abstract PO4-17-06: Real World Data: A single institute experience with neoadjuvant endocrine therapy for ER+ breast cancer — clinical response rates, clinical predictors of response and long-term outcomes following breast conserving surgery

Abstract Background: Neoadjuvant endocrine therapy (NET) in postmenopausal women (PMW) with large or locally advanced oestrogen receptor (ER)-rich breast cancer allows more women to be treated by breast-conserving surgery (BCS). A comprehensive analysis of the factors affecting clinical response to NET and the long-term safety of this strategy has been studied. Patients: A retrospective cohort was studied of 435 PMW (median age: 77 years; range: 50-98) with ER-positive breast cancer treated with NET (aromatase inhibition) (median duration: 6.8 months; range 3-43 months), between 2001-15. Clinical response was monitored throughout NET treatment with periodic 3D ultrasound measurements of the primary tumour. All patients went on to have surgery, 55% had adjuvant radiotherapy and all had adjuvant ET for at least 5 years. All patients had routine follow-up (median follow-up 12.3 years). To-date, this represents the largest cohort of patients treated with &amp;gt;3 months NET. Results: Clinical response to NET was excellent, with only 3.2% of tumours progressing on-treatment based on RECIST 1.1 criteria. Mean percentage reduction in tumour on NET was 71%. Response rate (partial/complete response) was 59% and response continued until 12 months and then levelled off. Following NET, over 92% of patients were suitable for BCS and 61% achieved clinical TNM down-staging. Multivariate analysis revealed that only ER level (response highest in patients with Allred scores 7 and 8), and percentage change in tumour volume by 6 weeks were significant predictors of overall clinical response to NET. Clinical response to NET was not associated with node status or tumour grade. BCS following NET had a local disease control rate of 89% (95%CI±0.06) at 10 years, but actuarial local recurrence at 10 years was only 7% in those having radiotherapy compared with 30% in the group who did not receive radiotherapy (P&amp;lt; 0.0001). In addition, the overall recurrence rate (P=0.028) was improved by radiotherapy irrespective of nodal status. Radiotherapy did not improve overall breast cancer-specific survival (BCSS). Systemic recurrence and BCSS was higher with greater nodal involvement. Most patients in this study died of other causes (14-year crude all-cause mortality was 71%). Conclusion: NET followed by BCS is an effective strategy in PMW with ER-rich breast cancer. Excellent clinical response rates are seen even in women with node-positive or high-grade disease. Less than 5% showed evidence of progression. Early response to NET predicts for long-term tumour volume reduction and NET can achieve continued tumour shrinkage for up to 1 year. NET followed by BCS appears a safe treatment approach and offers good long-term outcomes when BCS is followed by adjuvant radiotherapy. Citation Format: Arran K Turnbull, Carlos Martinez-Perez, Charlene Kay, Rebecca Swan, Lorna Renshaw, J Michael Dixon. Real World Data: A single institute experience with neoadjuvant endocrine therapy for ER+ breast cancer — clinical response rates, clinical predictors of response and long-term outcomes following breast conserving surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-06.