Citations

Abstract Background Hidradenitis suppurativa (HS) is a chronic, relapsing, debilitating skin disease characterized by deep‐seated nodules, abscesses and tunnels. Objectives To investigate the efficacy of bimekizumab using International Hidradenitis Suppurativa Severity Score System (IHS4) outcomes in patients with moderate to severe HS in the pooled BE HEARD I and II Phase 3 studies. Methods Patients received (initial/maintenance) bimekizumab 320 mg every 2 weeks (Q2W)/Q2W, bimekizumab Q2W/every 4 weeks (Q4W), bimekizumab Q4W/Q4W or placebo/bimekizumab Q2W. Change from baseline (CfB) in IHS4, IHS4 severity stages and the dichotomous IHS4‐55/75/90/100 (an improvement of at least 55%/75%/90%/100% in IHS4 from baseline) are reported to Week 48. Lesion count data by lesion type are reported to Week48. Results In total, 1014 patients were enrolled across BE HEARD I and II. At baseline, mean (standard deviation [SD]) IHS4 for bimekizumab‐treated patients ranged from 33.4 (25.4) for bimekizumab Q2W/Q2W to 36.0 (34.0) for bimekizumab Q2W/Q4W versus 30.6 (21.8) for placebo. At Week16, patients receiving bimekizumab demonstrated greater reductions in mean (SD) IHS4 from baseline, ranging from −17.2 (24.8) for bimekizumab Q4W/Q4W to −17.8 (21.1) for bimekizumab Q2W/Q2W versus −6.1 (16.3) for placebo. Proportions of patients with severe HS at baseline ranged from 83.7% (bimekizumab Q2W/Q2W) to 88.4% (bimekizumab Q2W/Q4W) and decreased by ~50% to Week48 across all treatment arms, ranging from 28.6% (placebo/bimekizumab Q2W) to 34.3% (bimekizumab Q2W/Q2W). Proportions of patients with IHS4 = 0 at Week48 ranged from 23.7% (bimekizumab Q2W/Q4W) to 26.7% (placebo/bimekizumab Q2W). At Week16, IHS4‐55, IHS4‐75, IHS4‐90 and IHS4‐100 thresholds were achieved by greater proportions of patients treated with bimekizumab versus placebo, while comparable improvements were seen across treatment arms from Week16 to Week48. At Week16, lesion counts were lower for patients treated with bimekizumab versus placebo, decreasing to comparable numbers across all groups at Week48. Conclusions Bimekizumab‐treated patients showed improvements across IHS4 outcome measures.

BACKGROUND: Lipodermatosclerosis (LDS) is a type of sclerosing panniculitis that predominantly involves the lower extremities and is characterized by erythema, hemosiderin pigmentation, and sclerotic skin lesions. LDS is a common reason for specialty consultations across clinical settings, including dermatology, vascular medicine, and occasionally the emergency department or internal medicine services. METHODS: To further evaluate the prevalence of venous hypertension in patients with LDS at the authors’ institution, they retrospectively reviewed the findings of lower extremity Doppler ultrasonography with or without segmental pressure (ie, venous ultrasonography) performed for adult patients with biopsy-confirmed LDS who were treated at the Clinic from January 1, 2000, through September 30, 2022. RESULTS: A total of 430 patients were included in the study. Venous ultrasonography findings were abnormal for 327 (76.0%) patients, whereas the other 103 (23.9%) patients had normal findings. Venous hemodynamics studies, including air plethysmography and continuous-wave Doppler ultrasonography, were performed for 33 patients with normal venous ultrasonography findings. Of these patients, 7 had mild valvular incompetence, 12 had abnormal calf muscle pump function, and 2 had pulsatility (backflow in the peripheral vein with elevated right atrial pressure) evident on continuous-wave Doppler ultrasonography. CONCLUSIONS: Overall, the findings extend previous observations that venous abnormalities are commonly present in patients with LDS and may contribute to its pathogenesis. However, a few patients with LDS have normal venous hemodynamics, which suggests that other factors also contribute to LDS pathogenesis.

Abstract Background Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with rising incidence and significant morbidity. Despite its growing burden, long-term data on clinical characteristics, management trends, and outcomes remain limited. Methods We conducted a 26-year multicenter retrospective cohort study of adults (≥18 years) diagnosed with NVO at Mayo Clinic sites between 1999 and 2024. Demographic, microbiologic, treatment, and outcome data were analyzed across five time periods. Predictors of treatment failure were assessed using a multivariable competing risk model. Results Among 1255 patients (median age 67; 66% male), lumbosacral involvement was most common (65%), and 21% had multilevel involvement. Pathogens were identified in 77%, most commonly Staphylococcus aureus (49%; Methicillin-susceptible S. aureus 37%, methicillin-resistant S. aureus 13%). Over time from 1999–2004 to 2020–2024, Gram-negative bacilli increased from 6% to 14% (P = .048). Comorbidities including chronic kidney disease (10% to 21%), active chemotherapy (6% to 11%), and immunosuppression (8% to 17%) increased significantly. Additionally, 1-year treatment failure declined (16% to 10%). In multivariable analysis, diabetes mellitus (subdistribution hazard ratio [sHR] 1.92, 95% CI 1.18–3.13) and multilevel involvement (sHR 1.67, 95% CI 1.17–2.38) were associated with increased incidence of treatment failure, while concurrent infections (sHR 0.57, 95% CI 0.37–0.87) and higher Charlson Comorbidity Index (sHR 0.62, 95% CI 0.43–0.90) were associated with lower failure. Conclusions This large multicenter cohort highlights increasing host complexity, shifting microbiology, and predictors of failure, emphasizing the importance of early risk stratification and tailored strategies, such as multidisciplinary evaluation and close follow-up of high-risk patients to improve outcomes.

Abstract Background A unified definition of prosthetic joint infection outcomes (PJI) is crucial for consistent data, study comparisons, and better care. This study systematically reviews how PJIs outcomes are defined, building on our prior research on native vertebral osteomyelitis and postoperative spinal infection.Figure 1Network plot illustrating the co-occurrence of outcome criteria in prosthetic joint infection studies. Edge thickness reflects the frequency of the co-occurrence of each criterion. Each plot highlights one criterion, namely (1) clinical signs, (2) imaging, (3) microbiology, (4) histopathology, (5) antibiotics-related, (6) surgical-related, (7) mortality. Methods We conducted a comprehensive search of the Cochrane, Embase, Medline, and Scopus databases for studies published after 2005 that clearly defined outcomes for PJI. Eligible studies included randomized controlled trials and cohort studies with a minimum of 10 patients diagnosed with PJI. Our methodology adhered closely to the PRISMA guidelines. Using a saturation approach, we extracted and grouped explicit definitions of PJI outcomes into thematic criteria. A network plot (Figure 1) was used to visualize how frequently these criteria appeared and how they co-occurred across the included studies. Results Out of 7,584 screened studies, 552 (7.3%) met the inclusion criteria. This pilot analysis included 49 randomly selected studies (8,162 patients), mostly retrospective (48/49, 98%), focusing on mixed joint replacements (25/49, 51%), two-stage exchanges (15/49, 31%), or mixed surgeries (24/49, 49%). Only 6/49 (12.2%) applied a society-endorsed definition, and 13/49 (26.5%) cited a reference for their outcome definitions. Overall, 32/49 (65.3%) explicitly defined "success," 35/49 (71.4%) defined "failure," and 16/49 (32.7%) defined both. Most studies (25/49, 51%) had follow-up periods over two years, and 14/49 (28.6%) included patient-reported outcomes, identifying 14 unique PROMs (most commonly UCLA, HHS, and KSS scores). Functional outcomes were assessed in 13/49 (26.5%) studies. We identified 16 distinct outcome criteria across seven categories: clinical signs, microbiology, imaging, histopathology, antibiotics-related, surgical-related, and mortality. Network analysis revealed strong links among clinical signs, microbiology, surgical factors, mortality, and imaging. Conclusion Our pilot study found major variation in PJI outcome definitions, with few standardized criteria. A consensus-driven approach is needed to strengthen evidence synthesis and advance patient care in PJI. Disclosures All Authors: No reported disclosures

Abstract Background The increased frequency of spinal surgeries has led to a rise in postoperative spine infections (PSIs), now recognized as the third most common surgical complication. Currently, there is no standardized definition of PSI, complicating clinical management and research. This meta-epidemiological study aimed to develop clear diagnostic criteria to assist clinicians and researchers in identifying and reporting PSIs consistently. 2020 PRISMA flow diagram Sankey diagram showing the distribution of combination of criteria or definitions used by the authors. This refers to 21 articles that used a definition derived by the authors. Methods Following PRISMA guidelines, a comprehensive literature search was conducted by a medical librarian using Ovid MEDLINE (March 14, 2024). Studies were included if they reported on at least ten adult patients diagnosed with PSI and provided clear diagnostic definitions. The primary objective was to evaluate existing PSI diagnostic criteria and categorize them into thematic clusters. We constructed standardized diagnostic combinations using 13 predefined criteria derived from clinical practice guidelines and prior research (Table 1).Characteristics of the included studies*Total can be more than 100% since some variables can be present in multiple categories.This refers to 21 articles that used a definition derived by the authors. For articles #411 and #630 categorization was not possible as the definition provided only information about the depth of infection and not the criteria for diagnosis. Article #1148 was included as, defining “presumed aspetic” cases meant, by definition, also defining infectious cases.Abbreviations. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), Centers for Disease Control and Prevention (CDC), The National Healthcare Safety Network (NHSN), Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA), Magnetic Resonance Imaging (MRI) Results From an initial 1,466 studies screened, 101 were included (Figure 1). Most studies were retrospective (91/101, 92.1%), and a majority (77/101, 76.2%) relied on established criteria such as those from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) or the CDC. Seven studies combined predefined criteria with additional detailed explanations. Among the remaining studies using independent definitions, clinical signs and symptoms were the most common criteria (13/24, 54.2%) (Table 1). Criteria were grouped into clinical, microbiological, and radiological categories, with most studies primarily using clinical criteria alone or in combination with microbiological or imaging findings (Figure 2). Conclusion There was no clear consensus in the literature on what defines a PSI. Our findings emphasize the necessity of establishing a standardized PSI definition that integrates clinical, microbiological, and radiological criteria. Implementing such a unified framework could enhance diagnostic accuracy, address existing limitations associated with hardware complications, wound drainage interpretations, and imaging ambiguities, and improve upon the current shortcomings of surveillance systems. Disclosures Jeremy D. Shaw, MD, Globus: Grant/Research Support|Purgo Scientific: Advisor/Consultant|Purgo Scientific: Stocks/Bonds (Private Company)

Abstract Background Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with considerable clinical burden. Although increasing literature has described its features and associated treatment failure, large-scale cohorts with long-term follow-up remain limited. Herein, we evaluated a large cohort of patients with NVO to characterize the clinical manifestations, management, and long-term outcomes, and to further explore factors associated with treatment failure.Table 1.Baseline characteristics of patients with native vertebral osteomyelitisTable 2.Treatment, failure rates, and mortality in patients with native vertebral osteomyelitis Methods We conducted a retrospective multicenter cohort study of adults (≥18 years) with NVO across Mayo Clinic sites between 1999 and 2024. Data on demographics, clinical manifestations, antimicrobial therapy, and surgical intervention were collected. Cumulative incidence of treatment failure was estimated as a function of follow-up accounting for the competing risk of death. Independent predictors of treatment failure were evaluated in a multivariable Cox regression model with time-dependent covariates.Table 3.Multivariable predictors of treatment failure in patients with native vertebral osteomyelitisFigure 1.Cumulative incidence of death and treatment failure following diagnosis of native vertebral osteomyelitis(A) Short-term (12-month) cumulative incidence of death and treatment failure (magnified view of the first year from panel B).(B) Long-term (up to 7 years) cumulative incidence of death (dotted orange line) and treatment failure (solid blue line). Results Among 1,255 patients included (median age 67 years; 66% male), lumbosacral involvement was most common (65%), with multilevel vertebral involvement ( >2 levels) in 21%. Epidural abscesses were present in 43%, paravertebral abscesses in 42%, and psoas abscesses in 20%. Pathogens were identified in 77%, most commonly S. aureus (50%; MSSA 37%, MRSA 13%), followed by Streptococcus species (22%), and Gram-negative bacilli (11%) (Table 1). The median total antibiotic duration was 59 days (IQR, 42–132). Surgical intervention was performed in 13% after a median of 2 days (IQR, 1-5). Treatment failure occurred in 162 patients during a median follow-up of 2.8 years (6-month and 5-year cumulative incidence were 11% and 14%, respectively), with the median time to failure of 3.1 months. Cumulative mortality was 12% at 6 months and 33% at 5 years (Table 2, Figure 1). Diabetes (HR 1.90, 95% CI 1.16–3.12), multilevel vertebral involvement (HR 1.75, 95% CI 1.22–2.51), and MRSA infection (HR 2.11, 95% CI 1.06–4.18) were independently associated with increased risk of treatment failure (Table 3). Conclusion This 25-year study highlights the persistent burden of treatment failure in NVO and associated risk factors, underscoring the importance of early recognition of high-risk features to optimize outcomes. Disclosures All Authors: No reported disclosures

Abstract Introduction Elevated levels of fetal hemoglobin (HbF) ameliorate sickle cell disease (SCD) manifestations. BEAM-101 is an investigational cell therapy comprising ex vivo base-edited autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) that directly target the HBG1/2 promoters to disrupt BCL11A binding, switching production from sickle (HbS) to majority anti-sickling HbF. We present ongoing data from the BEACON study (NCT05456880), a Phase 1/2, single-arm, open-label study evaluating a single dose of BEAM-101 in individuals with SCD and severe vaso-occlusive crises (sVOCs). Methods Eligible patients were aged 12–35 years with SCD and ≥4 sVOCs in the 2-year period prior to informed consent. After mobilization with weight-based or tiered fixed-dose plerixafor, autologous CD34+ HSPCs were collected by leukapheresis and genetically modified with an adenine base editor. Following conditioning with pharmacokinetically adjusted myeloablative busulfan (target cumulative AUC 80 hr*mg/L), patients received a single dose of BEAM-101 (≥3.0×106 viable CD34+ cells/kg). Patients were then monitored for neutrophil and platelet engraftment, adverse events (AEs), total Hb, Hb fractions, % F-cells, hemolysis markers, sVOCs, and additional protocol endpoints for up to 24 months. Results As of June 16, 2025, enrollment has been completed and 46 patients have initiated mobilization. Of the 26 patients who have received BEAM-101, mean duration of follow-up was 6.2 (range 1.0–18.7) months. Baseline demographics were: age 18–34 years, 24 βS/βS genotype, 21 self-reported Black/African American, and 11 female. One patient, who successfully engrafted and obtained stable HbF levels >60%, withdrew consent 5 months post-infusion. For the 26 treated patients, the median number of stem cell collection cycles was 1 (range 1–4); 18 (69.2%) required a single cycle, 4 required 2 cycles, and 4 required >2 cycles. Target cell dose was achieved with a median of 3 (1–12) collection days. Patients received a mean BEAM-101 dose of 8.4 (range 3.2–23.4) ×106 viable CD34+ cells/kg. By the data cut, patients achieved neutrophil (n=26) and platelet (n=24) engraftment at a median of 18 (12–30) days and 19 (11–50) days, respectively, with a median duration of 7 (4–17) days of neutropenia. Of the 24 evaluable patients, 9 (37.5%) achieved platelet engraftment without requiring platelet transfusion through the transplant process. No patients had ≥Grade 3 AEs or serious AEs related to BEAM-101. One patient died due to respiratory failure, assessed as likely related to busulfan conditioning, 4 months post-infusion as previously reported. Mean total Hb increased to 12.1 (range 9.0–14.7) g/dL by Month (M) 1 (n=24), 15.6 (11.9–18.6) g/dL by M6 (n=11), and was sustained through follow-up. Four patients had total Hb levels above the normal range beyond M6 without any associated clinical manifestations or need for therapeutic intervention. Erythropoietin levels trended towards normal in all patients, including those with elevated total Hb. Mean endogenous HbF (HbF/[HbF+HbS]) was >60% and HbS was <40% by M1, which was sustained through last follow-up. At M6, mean % F-cells were 99.2% (97.0–99.9; n=10) and mean HbF/F-cell was 20.8 (18.0–23.9; n=9) pg, exceeding the protective threshold of 10 pg against sickling. Peripheral blood editing was at a mean of 68.5% by M3 (n=16), 69.6% by M6 (n=10), and 72.8% by M12 (n=5). Hemolysis markers and sickling parameters normalized or improved for all patients. No patients experienced any investigator-reported sVOCs post-engraftment. Conclusions The BEAM-101 treatment process is characterized by a low number of mobilization and collection cycles and high editing efficiency, resulting in rapid neutrophil and platelet engraftment and robust pancellular HbF expression, with durability observed up to 18 months. Additionally, there is a corresponding reduction in HbS levels to <40%, and improvements or resolution of hemolysis parameters and anemia, along with resolution of investigator-reported sVOCs post-engraftment. The safety profile of the BEAM-101 treatment regimen is consistent with busulfan conditioning, autologous HSCT, and underlying SCD. These results demonstrate the potential for base editing of the HBG1/2 promoters as a safe and effective therapeutic modality for the treatment of SCD that also has the potential to minimize hospitalization and treatment process burden for patients, families, and sites.

ABSTRACT Background Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis highly associated with systemic comorbidities. Accurate diagnosis and treatment remain challenging due to its rarity and clinical mimickers. Objectives To evaluate demographic, clinical features and treatment outcomes in patients referred with suspected PG at a tertiary wound care centre. Methods A prospective observational study was conducted of patients referred for suspected PG between April 2021 and June 2023. Demographic, clinical and laboratory data, including biopsies and tissue cultures, were collected. Patients were categorised as having PG vs alternative diagnoses based on diagnostic criteria from Su, Maverakis and the PARACELSUS score. Results Of 60 patients (female, 51.7%; mean [SD] age 52.9 [14.0] years), 44 (73.3%) met at least one published diagnostic criterion for PG. The most common comorbidity was IBD (63.6%), followed by inflammatory arthritis (25.0%) and monoclonal gammopathy of undetermined significance (MGUS) (4.5%). Systemic corticosteroids were used by 40.9% of patients before referral, but steroid‐sparing agents and biologics were the primary treatments after consultation. Biologics and steroid‐sparing agents were associated with significant improvement in disease activity using the PGA score (average score decreased from 2.3 to 1.5, p < 0.005), with 40.9% achieving complete remission. Elevated serum inflammatory markers and faecal calprotectin were observed in PG patients but absent in non‐PG cases. Conclusions These prospective data support previously published rates of association between PG and systemic comorbidities. Steroid‐sparing anti‐neutrophilic and targeted therapies are effective steroid‐sparing strategies in managing PG. Small sample size and referral bias may limit generalisability.

Importance Accurate classification and reliability in assessment for lesions of hidradenitis suppurativa (HS) by investigators is critical to the determination of responder status and to overall data quality in clinical trials. Objective To establish consensus-based morphological definitions of HS lesions and guidance statements that standardize investigator lesion assessments for implementation in clinical trials. Evidence Review Health professionals (primarily dermatologists) with expertise in the measurement of HS disease activity as well as novice raters completed a preliminary questionnaire in which participants were asked to assess images of HS lesions and provide qualitative feedback on their decision making. Based on this feedback, detailed morphologic definitions for lesions and guidance statements that standardize lesion assessments were formulated and presented for consensus voting in 2 electronic Delphi surveys. A virtual group discussion after round 1 supported participants in round 2 voting. Findings Response rates were 84.7% (50 of 59), 86.0% (43 of 50), and 90.9% (40 of 44) in the preliminary, electronic Delphi round 1, and electronic Delphi round 2 surveys, respectively. Morphological definitions for 11 lesion types achieved the prespecified 70% consensus threshold, with 9 definitions reaching at least 90% agreement. After 2 electronic Delphi rounds, 16 of 18 guidance statements achieved the prespecified consensus threshold, with 13 statements receiving endorsement from more than 80% of participants. Two guidance statements related to assessment of tunneled plaques with multiple openings and assessment of scalp lesions failed to reach consensus. Conclusions and Relevance Common morphologic definitions and guidance that standardize assessment of HS lesions can be implemented in clinical trial protocols and investigator trainings with the goals of improving accuracy and reliability of investigator ratings.