Dermatology Specialists

Abstract Two bispecific antibodies, glofitamab and epcoritamab, are CD20xCD3 targets approved to treat R/R DLBCL. Two antibody drug conjugates, brentuximab vedotin, with a CD30-directed monoclonal antibody, is approved for cHL and R/R DLBCL, and polatuzumab vedotin, with a CD79b directed monoclonal antibody, is approved for R/R DLBCL. Unique mechanisms of action for each agent, the path to FDA approval from preclinical stage, FIH trials and clinical trials for each agent, as well as comparisons of adverse events between the two classes of therapeutic agents are shown, as well as how these two distinct classes of agents developed mechanistically and clinically for lymphomas, hematologic cancers with generally poor prognosis. Glofitamab was evaluated and complete responses were ongoing at 12 months. The 12-month PFS was 37% (95% CI, 28 to 46). Discontinuation of glofitamab due to adverse events occurred in 9% of the patients. Glofitamab combined with tislelizumab in R/R DLBCL was also evaluated in a single-center pilot trial. In a study investigating epcoritamab, the ORR was 63.1% (95% CI, 55.0 to 70.6) and the CR rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and CR rates were similar across key prespecified subgroups. The most common TEAEs were CRS (49.7%); (grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). ICANS occurred in 6.4% of patients with one fatal event. Epcoritamab also induced potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. Brentuximab vedotin was shown to be effective in R/R DLBCL in the ECHELON-3 trial, a randomized, double-blind, placebo-controlled, multicenter, phase 3 study comparing BV + Len + R with placebo + Len + R. With a median follow-up of 16.4 months, the mOS was 13.8 months with BV + Len + R versus 8.5 months with placebo + Len + R (HR, 0.63 [95% CI, 0.45 to 0.89]). The mPFS was 4.2 months with BV + Len + R versus 2.6 months with placebo + Len + R (HR, 0.53 [95% CI, 0.38 to 0.73]). The ORR was 64% [95% CI, 55 to 73] with BV + Len + R and 42% (95% CI, 33 to 51) with placebo + Len + R; CR rates were 40% and 19%, respectively. TEAEs occurred in 97% of patients in both arms, including neutropenia, thrombocytopenia, diarrhea, and anemia. Polatuzumab vedotin was also evaluated in R/R DLBCL. Polatuzumab vedotin plus bendamustine and rituximab (pola + BR) received regulatory approvals for R/R DLBCL based on primary results from the randomized arms of the GO29365 study. Significant survival benefit with pola + BR vs BR persisted (mPFS 9.2 vs 3.7 months [HR, 0.39; 95% CI, 0.23-0.66]; mOS, ([12.4 vs 4.7 months [HR 0.42; 95% CI 0.24-0.72]). Pola + BR was shown to be an effective treatment option for patients with R/R DLBCL, with a well-characterized and manageable safety profile. Citation Format: Priya Hays. Bispecific T-cell engagers and antibody-drug conjugtes for the treatment of lymphomas [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A056.

Background: Multiple studies demonstrate that the Alvarado Score is less effective than other studies in predicting the incidence of patients with suspected acute appendicitis. It does not distinguish between ages and does not suggest a clinical stage of the disease. However, its use is still current in our unit and in most hospitals in our country. General Objective: To identify the utility of the Alvarado Score in patients with suspected acute appendicitis in relation to imaging results. Materials and Methods: Descriptive, observational, cross-sectional, retrospective study, which was carried out with 62 records of patients with suspected acute appendicitis and who were requested imaging studies at the Regional General Hospital 1 of Orizaba, Veracruz with the suspected diagnosis of Acute Appendicitis during the period from December 1, 2017 to November 30, 2022. Patients of any age group and both sexes who came to the emergency service with pain in the right iliac fossa and classified with the Alvarado scale that met the selection criteria were included. This study was conducted from March 1 to September 30, 2023. Data analysis included descriptive statistics for qualitative variables using frequencies and percentages, as well as measures of dispersion. For quantitative variables, such as mean and standard deviation, the Fisher exact test was used between variables with two categories based on the nature of the categorical variables. SPSS 23 and GraphPad Prism 8 software were used. Resources and infrastructure: those of the institution, the patients, and the researcher. Group experience: There is a master's degree in science and a radiologist with experience in ultrasound and CT interpretation. A resident physician who will carry out the activities of the research project. Results: The female sex predominated with a frequency of 40 patients (56.33%) with a mean age of 28.80 years, standard deviation +/- 19.36 (95% CI 22.61-34.99), of the male sex a frequency of 31 patients (43.66%) was observed with a mean age of 28.16 years, standard deviation +/- 17.69, the time of onset of symptoms: 35 patients (49.3%) began with symptoms at 24 hours, followed by 15 patients (21.1%) at 12 hours, 11 patients (15.5%) at 72 hours, 7 patients reported onset of symptoms at 48 hours (9.9%). The relationship between the Alvarado scale and imaging studies was identified using Fisher's exact test. The P value was 0.8791, which is considered statistically insignificant. Conclusion: The Alvarado score has proven to be a useful, simple, noninvasive, and rapid tool for guiding the diagnosis of acute appendicitis. However, due to its low specificity, the use of imaging studies is always recommended to confirm suspected diagnoses.

Purpose: Cardiovascular disease (CVD) is the leading cause of death among patients with prostate cancer (PC). Androgen deprivation therapy (ADT) remains the standard of care for advanced PC. Since 2010, the U.S. FDA has required warning labels for gonadotropin-releasing hormone agonists about increased risk for diabetes and some CVDs. This observational, retrospective, real-world study evaluated the risks of a first cardiovascular event within 3 years after initiation of ADT in patients with PC, with or without the presence of ≥ 1 of 3 cardiometabolic comorbidities: diabetes mellitus (DM), hypertension, and hyperlipidemia. Materials and Methods: Retrospective data (2010-2019) from a large administrative U.S. claims data set were analyzed to examine risk of first cardiovascular event based on the presence/absence of target comorbidities, alone or combined, using Cox regression modeling. Results: Of 10,530 patients with PC receiving ADT, 934 (8.9%) experienced a postindex cardiovascular event. Compared with patients without any of the 3 comorbidities, risk of cardiovascular events was greatest for patients with all 3 comorbidities (hazard ratio [HR], 95% confidence interval [CI], 2.15 [1.73-2.68]; P < .0001), followed by those with DM alone (HR [95% CI], 1.72 [1.28-2.31]; P = .0003). Having DM + hypertension or hypertension + hyperlipidemia also increased risk of a cardiovascular event. Conclusions: Patients with PC and comorbid DM, hypertension, and hyperlipidemia treated with ADT are at increased risk of a cardiovascular event after ADT initiation compared with patients without these comorbidities. This study provides a straightforward method to evaluate men with PC before starting ADT to identify patients at greatest risk for experiencing a cardiovascular event.

Patients with moderate-to-severe atopic dermatitis (AD) who discontinue dupilumab need additional therapeutic options. Lebrikizumab's distinct mechanism of action may provide that alternative treatment. We evaluated efficacy and safety of lebrikizumab in adults and adolescents with moderate-to-severe AD previously treated with dupilumab. In the open-label ADapt trial, patients who discontinued dupilumab due to inadequate response, adverse events (AEs)/intolerance, or other reasons received lebrikizumab 250-mg every 2weeks (Q2W) following 500-mg loading dose at baseline/week2, through week16, with optional topical therapy. From weeks16-24, responders (≥ 75% improvement in Eczema Area and Severity Index [EASI75] or Investigator's Global Assessment score 0/1 with ≥ 2-point improvement from baseline) received lebrikizumab every 4weeks; inadequate responders continued lebrikizumab Q2W. The primary endpoint was EASI75 at week16 in the intent-to-treat population; EASI75 was also analyzed by reason for dupilumab discontinuation. Secondary and exploratory efficacy endpoints were assessed throughout. Among the 86 patients enrolled, primary reasons for stopping dupilumab were inadequate response (n = 48, 55.8%), AEs/intolerance (n = 14, 16.3%), and other reasons (n = 24, 27.9%). Fifty-nine patients (68.6%) completed week16; 52 patients (60.5%) completed week24. At weeks16 and 24, respectively, response rates were 57.4% (35/61) and 60.0% (33/55) for EASI75; 53.2% (25/47) and 61.5% (24/39) for Pruritus Numeric Rating Scale ≥ 4-point improvement; and 83.0% (44/53) and 83.0% (39/47) for Dermatology Life Quality Index ≥ 4-point improvement. Most treatment-emergent AEs were mild/moderate. Serious AEs and discontinuations due to AEs were reported by 2 (2.3%) and 5 (5.8%) patients, respectively. Of the 10 patients who discontinued dupilumab due to eye-related events, facial dermatitis, or inflammatory arthritis, none reported similar events with lebrikizumab. Results suggest that lebrikizumab provides meaningful improvements in skin clearance, itch, and quality of life in dupilumab-experienced patients with moderate-to-severe AD, with a safety profile consistent with other lebrikizumab phase3 trials. ClinicalTrials.gov identifier, NCT05369403.

BackgroundGepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial that selectively inhibits bacterial replication through a distinct binding site, unique mechanism of action and, for most target pathogens, well-balanced inhibition of two Type II topoisomerase enzymes (DNA gyrase and topoisomerase IV). Gepotidacin was recently approved by the FDA for the treatment of uncomplicated urinary tract infections (uUTI). This study evaluated the effects of several antimicrobial susceptibility testing (AST) variables on standardized (i.e., CLSI, EUCAST) testing methods for key uUTI uropathogens.Variables shown to significantly impact gepotidacin BMD MICs and/or DD zone for EnterobacteralesMethodsThe in vitro activity of gepotidacin and levofloxacin was evaluated using 4 CLSI AST methods: broth microdilution (BMD), broth macrodilution (MD), agar dilution (AD) and disk diffusion (DD). 85 clinical isolates were included for MIC testing and 90 isolates for DD, including E. faecalis (EF), S. saprophyticus (SS), and several Enterobacterales species known to be implicated in uUTI. Variables (BMD and DD only) including but not limited to inoculum concentration, temperature, atmospheric conditions, pH, and urine were tested.ResultsGepotidacin mean reference BMD MICs varied no more than 1 dilution over multiple days, for all species tested. MICs were comparable between the 3 MIC testing methods with MICs for 84 of 85 isolates within ± 1 dilution. Reference gepotidacin mean disk results varied by approximately 1-2 mm over multiple testing days. Mueller Hinton agar data was similar for DD with the exception of SS and Remel in which the majority of results were > 3mm larger. Variables shown to significantly impact gepotidacin BMD MICs and/or DD zone for Enterobacterales are shown in the table below.Results were similar for SS and EF with the exception of EF and SS DD zones being more impacted by inoculum variation and no impact of temperature on EF and SS MICs and DD zones.ConclusionWhen performing susceptibility testing with gepotidacin it is important to control the following variables, which were shown in this study to have the most impact on results: high inoculum concentration, high temperature (for Enterobacterales only), pH, incubation in 5% CO2 (for DD only) and testing of BMD MICs in urine.DisclosuresNicole E. Scangarella-Oman, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Josh West, BS, GSK: Employee|GSK: Stocks/Bonds (Public Company)

Abstract This study investigates the technical feasibility of achieving carbon neutrality in campus heating through integration of on-site PV or solar thermal and thermal storage systems. Using a simulation case study based on a real, federally owned campus in Ontario, Canada, various scenarios were explored to assess their potential to meet Canadian 2050 net-zero emission targets while minimizing electrical demand. Results indicate that multiple scenarios employing a combination of PV, solar thermal, BTES, and PTES on a district energy system can achieve carbon neutrality. However, variations in annual consumption, peak demand, and land use highlight the trade-offs that exist in evaluating the feasibility of net-zero emission campuses.