Consensus Definition Research Articles

Dietary and lifestyle indices for hyperinsulinemia and odds of MAFLD in overweight and obese children and adolescents

Lifestyle and dietary intake play a pivotal role in development of metabolic dysfunction-associated fatty liver disease(MAFLD). We performed this cross-sectional study to evaluate the association between lifestyle and dietary insulinemic potential and odds of MAFLD in overweight and obese children and adolescents. The insulinemic potential of the diet and lifestyle was assessed by computing the scores of the empirical dietary index for hyperinsulinemia(EDIH), the empirical lifestyle index for hyperinsulinemia(ELIH), the empirical dietary index for insulin resistance(EDIR), and the empirical lifestyle index for insulin resistance(ELIR). MAFLD was diagnosed according to the consensus definitions. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. A total of 334 (49.1% boys) with mean ± SD age and BMI-for-age-Z-score of 9.3 ± 1.8 and 2.55 ± 0.69, respectively, were enrolled. After adjusting for all potential confounders, participants in the highest quartile of ELIH score had greater odds of developing MAFLD (OR:3.50;95%CI:1.49–8.22) compared with those in the lowest quartile. This association remained significant among boys and pubertal ones. However, no significant association between EDIH, EDIR, or ELIR and odds of MAFLD was found. Our study suggests that the collective insulinemic potential of dietary intake, BMI, and physical activity is associated with increased odds of MAFLD.

Protocol on a systematic review of nomenclature and outcomes in children with complex critical illness in Paediatric Critical Care: The basis for consensus definition.

Paediatric Critical Care (PCC) supports the recovery of children with severe illness. In the UK, there are 30 PCC units with a total of approximately 400 beds. There is constant demand for these beds with a mean five-day length of stay and admissions increasing at a greater rate than age-specific population growth. Prolonged stay patients account for approximately half of all PCC patient bed days. Children with complex critical illness (CCI) need input from multiple different teams alongside support for their family. CCI often become prolonged PCC-stay patients too. Internationally, there is variation in the definition of CCI, this creates service variation and tensions around what resources can be provided including discharge planning, provision, and support. Objective: The face of Paediatric Critical Care, in the UK and internationally has changed over the last ten years with a growing cohort of complex critically ill patients. This systematic review aims to look at current nomenclature, criteria, and outcome measures of priority in this undefined patient population. Inclusion criteria: All types of studies examining children with complex critical illness (age <18 years) admitted to any paediatric critical care. The review is registered on Prospero. Medline, Embase, Maternity and Infant care, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Trip database will be searched from 2014 to May 2024. The search was limited to ten years as children with complex critical illness are a relatively new concept within PCC. Therefore, the timeline was limited to increase the accuracy and applicability of the review. Search limits included all languages, excluded the setting of neonatal intensive care, and age>18 years old. The final search strategy was developed in Medline and peer-reviewed by a health research librarian not involved in the study. This was translated to other databases as appropriate. Four independent reviewers will screen citations for eligible studies and perform data extraction. A systematic review methodology has been used to develop a broad understanding of the literature which will be used to develop further work in this area. Using a rigorous and stepwise approach, the whole spectrum of scientific publications on children with complex critical illness in paediatric intensive care will be reviewed, ensuring this study is as comprehensive as possible. This includes quantitative, qualitative, theoretical, and grey literature. A limitation of this systematic review is the use of many terms to describe children with complex critical illness in the literature resulting in a high number of publications on this topic.

Call for a consensual definition of dyslipidemia in coronary angiography trials

Dyslipidemia is extensively analyzed in clinical trials investigating its role as a risk factor for coronary artery disease (CAD). However, its definition varies vastly among studies, leading to different attributions to the variable dyslipidemia. The objectives of this study are to verify the hypothesis of a lack of a consensual definition of dyslipidemia in coronary angiography studies and to propose a consensual definition of dyslipidemia, considering the influence of each serum lipid parameter on mortality. A systematic search of coronary angiography studies focusing on dyslipidemia was conducted. We listed definitions and their references in the 258 articles the research found. Out of the 258 articles retrieved in the search, 52 studies (20%) provided a definition of dyslipidemia, and 20 (8%) mentioned the source. We identified 39 different definitions. To mitigate misinterpretations of cardiovascular risk factors, we propose the use of the “lipid triad” components to define dyslipidemia: LDL-cholesterol &amp;gt;3.0 mmol/L for primary prevention and &amp;gt;2.6 mmol/L or &amp;gt;1.4 mmol/L for secondary prevention in patients over/under 75 years old, respectively; or HDL-cholesterol &amp;lt;1.3 mmol/L (women) and &amp;lt;1.0 mmol/L (men); or triglycerides &amp;gt;1.7 mmol/L.

Septic Cardiomyopathy: Difficult Definition, Challenging Diagnosis, Unclear Treatment

Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap in critical care medicine. It is an often-underdiagnosed complication of sepsis. The only widely accepted aspect of its definition is that SCM is a transient myocardial dysfunction occurring in patients with sepsis, which cannot be attributed to ischemia or pre-existing cardiac disease. The pathogenesis of SCM appears to be multifactorial, involving inflammatory cytokines, overproduction of nitric oxide, mitochondrial dysfunction, calcium homeostasis dysregulation, autonomic imbalance, and myocardial edema. Diagnosis primarily relies on echocardiography, with advanced tools such as tissue Doppler imaging (TDI) and global longitudinal strain (GLS) providing greater sensitivity for detecting subclinical dysfunction and guiding therapeutic decisions. Traditional echocardiographic findings, such as left ventricular ejection fraction measured by 2D echocardiography, often reflect systemic vasoplegia rather than intrinsic myocardial dysfunction, complicating accurate diagnosis. Right ventricular (RV) dysfunction, identified as a critical component of SCM in many studies, has multifactorial pathophysiology. Factors including septic cardiomyopathy itself, mechanical ventilation, hypoxemia, and hypercapnia—particularly in cases complicated by acute respiratory distress syndrome (ARDS)—increase RV afterload and exacerbate RV dysfunction. The prognostic value of cardiac biomarkers, such as troponins and natriuretic peptides, remains uncertain, as these markers primarily reflect illness severity rather than being specific to SCM. Treatment focuses on the early recognition of sepsis, hemodynamic optimization, and etiological interventions, as no targeted therapies currently exist. Emerging therapies, such as levosimendan and VA-ECMO, show potential in severe SCM cases, though further validation is needed. The lack of standardized diagnostic criteria, combined with the heterogeneity of sepsis presentations, poses significant challenges to the effective management of SCM. Future research should focus on developing cluster-based classification systems for septic shock patients by integrating biomarkers, echocardiographic findings, and clinical parameters. These advancements could clarify the underlying pathophysiology and enable tailored therapeutic strategies to improve outcomes for SCM patients.

Substance-involved child-to-parent violence.

Child-to-parent violence (CPV) is associated with youth substance problems; however, CPV which is substance-involved (SU-CPV) is specifically excluded from the consensus definition of CPV and few studies have explored the familial context surrounding SU-CPV. This study utilised the I3 model to explore associations between parental monitoring, parental intrusiveness, affective reactivity, concurrent reactive CPV and SU-CPV in an Australian community sample of caregivers. A total of 119 caregivers experiencing abusive CPV (frequent and severe) completed an online survey reporting on incidence of CPV from 12 to 24-year-olds under their care, parenting behaviours, traits of the young person and their experience of SU-CPV. Poor parental monitoring was positively associated with SU-CPV, and this relationship was stronger at higher levels of affective reactivity in the young person. There were no significant three-way interactions. SU-CPV may be most likely to occur where opportunity for child substance use is high, and risk of escalation is also high. These findings should be used to inform current CPV intervention, which may otherwise neglect youth substance use.

P-1024. Fungal Pneumonia and Severe Neutropenia: Risk Factors for Increased 90 Day Mortality

Abstract Background Invasive fungal infections (IFI) carry a high mortality risk in hematologic malignancy; the majority being pulmonary infections. Diagnosis is based on consensus definitions of host factors, clinical features and mycologic evidence. In previous studies, increased mortality is associated with delays in therapy and failure of neutrophil recovery; however, use of salvage posaconazole may have improved outcomes. We sought to identify risk factors associated with higher 90-day mortality in these patients. Methods Patients at an NCI designated comprehensive cancer center from 06/2021 – 07/2023 with hematologic malignancy, severe neutropenia and a diagnosis of IFI and receiving posaconazole for treatment with verified therapeutic drug monitoring were identified. Demographic, clinical and laboratory data were evaluated to identify risk factors for increased mortality within 90 days of diagnosis of pulmonary IFI. The diagnosis was based on international consensus definitions. Results A total of 39 patients were identified. 18 (46.2%) were diagnosed with acute myeloid leukemia and 13 (33.3%) had undergone bone marrow transplantation. Median time from diagnosis to treatment initiation was 2 days and 17 (43.6%) patients received combination therapy with multiple antifungal agents. Bronchoscopy with bronchoalveolar lavage was performed in 34 (87.2%) and of those a microbiologic diagnosis found in 5 (14.7%). Day 90 mortality was 56.0% (n=14). Survivors were more likely to have initiation of antifungal therapy within 7 days (96.0% vs 64.3%, p=0.016) and received liposomal amphotericin B as part of their initial therapy (72.0% vs 42.9%, p=0.009). Patients receiving corticosteroids or who failed to have neutrophil recovery tended to have higher mortality, but this did not achieve statistical significance. Combination therapy and receipt of granulocyte or granulocyte-macrophage colony-stimulating factors were not associated with improved day 90 mortality. Conclusion Early recognition and initiation of antifungal therapy in high-risk neutropenic patients with hematologic malignancy with IFI and initial therapeutic regimens including liposomal amphotericin B may be associated with improved outcomes. Disclosures All Authors: No reported disclosures

P-2286. Invasive Fungal Infections in Patients Treated with Bruton Tyrosine Kinase Inhibitors: a Systematic Review and Meta-Analysis

Abstract Background Controversy surrounds the true incidence of invasive fungal infections (IFIs) in patients on Bruton tyrosine kinase inhibitors (BTKIs) due to incomplete epidemiological data. This systematic review and meta-analysis evaluated the prevalence and risk factors of IFIs in BTKI-treated patients.Figure 1.Forest plot for the prevalence of invasive fungal infections in patients treated with Bruton tyrosine kinase inhibitors This study was registered under PROSPERO (CRD42024523198). The prevalence was calculated using a generalized linear mixed model random-effects meta-analysis and presented as effect sizes with 95% confidence intervals (CIs). IFIs were defined according to The European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) consensus definitions. Methods Studies up to April 17, 2024, from Pubmed, Scopus, and Embase, including observational studies reporting prevalence and/or associated risk factors of IFIs with at least 30 BTKI-treated patients, were searched and analyzed. IFIs were defined according to standard definitions. The prevalence of IFIs and odds ratio (ORs) for the risk factors associated with IFIs were reported alongside 95% confidence intervals (CIs).Figure 2.Forest plot for the prevalence of proven/probable invasive fungal infections in patients treated with Bruton tyrosine kinase inhibitors according to the World Health Organization regions Results This study included 14,679 patients across 24 studies (13,981 with hematologic malignancies and 67 with chronic graft-versus-host disease). Of these, 15 studies specifically included only proven/probable IFIs (ppIFIs) (Figure 1 and Table 1). The overall IFI prevalence was 2.23% (95% CI 1.73-2.88%), and for ppIFIs, was 2.64% (95% CI 1.87-3.70%). The median durations from BTKI initiation to ppIFI onset ranged from 24-186 days. The highest prevalence of ppIFIs was in patients with mantle cell lymphoma (7.60%, 95% CI 3.14-17.26%), followed by chronic lymphocytic leukemia (3.01%, 95% CI 1.93-4.66%), and Waldenström's macroglobulinemia (2.18%, 95% CI 0.33-12.96%). Regional ppIFI prevalence was the highest in Western Pacific (7.58%, 95% CI 3.19-16.94%), followed by Europe (2.60%, 95% CI 1.49-4.49%) and America (2.37%, 95% CI 1.59-3.52%) (Figure 2). The most common ppIFIs were invasive aspergillosis (1.78%, 95% CI 1.24-2.57%), followed by pneumocystosis (0.80%, 95% CI 0.16-3.81%), invasive candidiasis (0.40%, 95% CI 0.14-1.16%), and cryptococcosis (0.33%, 95% CI 0.19-0.56%). Corticosteroid use was significantly associated with ppIFIs (OR 5.03, 95% CI 2.31-10.92) (Figure 3).Figure 3.Forest plot for risk factors associated with proven/probable invasive fungal infections in patients treated with Bruton tyrosine kinase inhibitorsGRADE = Grading of Recommendations Assessment, Development and Evaluation certainty of evidence; OR = odds ratio. Odds ratios were directly extracted from regression analysis or manually calculated by comparing associated factors between patients with and without invasive fungal infections. Conclusion In conclusion, the prevalence of IFIs in patients treated with BTKIs (mostly ibrutinib) reaches 2%, and up to 7.6% in those with mantle cell lymphoma, indicating a significant risk. Antifungal prophylaxis should be customized based on individual underlying diseases and steroid use.Table 1.Characteristics of included studies BTKI = Bruton tyrosine kinase inhibitor; cGVHD = chronic graft-versus-host disease; CLL = chronic lymphocytic leukemia; DLBCL = diffuse large B-cell lymphoma; EORTC/MSGERC = the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium; FL = follicular lymphoma; HCL = hairy cell leukemia; HM = hematologic malignancies; LPL = lymphoplasmacytic lymphoma; MCL = mantle cell lymphoma; MZL = marginal zone lymphoma; NA = not available; NHL = non-Hodgkin’s lymphoma; PCNSL = primary central nervous system lymphoma; PLL = prolymphocytic leukemia; RS = Richter’s syndrome; SCNSL = secondary central nervous system lymphoma; SLL = small lymphocytic lymphoma; USA = United States of America; WM = Waldenström's macroglobulinemia Disclosures Shmuel Shoham, MD, F2G: Grant/Research Support Veronica Dioverti, MD, AlloVir: Grant/Research Support|Regeneron: Advisor/Consultant|Regeneron: Grant/Research Support Nitipong Permpalung, MD, MPH, CareDx: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|ClearView: Advisor/Consultant|IMMY Diagnostics: Grant/Research Support|Merck: Grant/Research Support|Pearl Diagnostics: Grant/Research Support|Pulmicide: Advisor/Consultant|Scynexis: Grant/Research Support

P-1013. Incidence and Risk Factors for Fungal Infection after CD19-targeted Chimeric Antigen Receptor T cell Therapy for Non-Hodgkin Lymphoma

Abstract Background Chimeric antigen receptor T cell therapy (CAR T) is highly effective for the treatment of non-Hodgkin lymphoma (NHL); however, recipients are at risk of infectious complications. Infections following CAR T are predominantly bacterial or viral; nevertheless, a subset of recipients develop invasive fungal disease (IFD). The limited evidence guiding antifungal prophylaxis (PPx) led us to investigate the incidence and risk factors for IFD at our center. Legend: DLBCL=diffuse large B-cell lymphoma; MCL=mantle cell lymphoma; tFL=transformed follicular lymphoma; PMBCL=primary mediastinal large B-cell lymphoma; HGBCL= high-grade B-cell lymphoma; autoHCT=autologous hematopoietic cell transplant; alloHCT=allogeneic hematopoietic cell transplant; CAR =chimeric antigen receptor; Axi-cel=axicabtagene ciloleucel; Brexu-cel=brexucabtagene autoleucel; Tisa-cel=tisagenlecleucel; CRS=cytokine release syndrome; ICANS= immune effector cell-associated neurotoxicity syndrome; IEC-HS/MAS= immune effector cell-associated HLH-like syndrome/macrophage activation syndrome; IgG=immunoglobulin G; G-CSF=granulocyte colony-stimulating factor Methods Adults with NHL who received commercial CAR T between January 2018 and February 2021 at MD Anderson Cancer Center were retrospectively identified. Demographics, oncologic history, and complications related to therapy were collected. Consensus definitions were used to define probable and proven IFD. Patients were observed for 1 year after CAR T or until death, whichever occurred first. Routine antifungal PPx was administered per institutional protocol. This database was built with funds from Merck. Legend: IFD=invasive fungal disease; PJP=Pneumocystis jirovecii pneumonia Results A total of 219 patients were identified (Table 1). Most patients had an underlying diagnosis of diffuse large B cell lymphoma (73.5%) and received axicabtagene ciloleucel (93.6%). Therapy related toxicities included: cytokine release syndrome (CRS) (88.1%), immune effector cell-associated neurotoxicity syndrome (ICANS) (58.9%) and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) (8.2%). Sixteen patients (7.3%) developed IFD, including 9 (4.1%) mold infections (Table 2). In univariate analysis (Table 3a), IEC-HS, grade 4 CRS, grade 4 ICANS, and any infection within 30 days prior to CAR T were associated with IFD. In multivariate analysis (Table 3b), grade 4 CRS, grade 4 ICANS, and any infection within 30 days prior to CAR T were independent predictors for IFD. Factors associated with mold infections in univariate analysis (Table 3c) included IEC-HS, grade 4 CRS, grade 4 ICANS, steroid use, prior hematopoietic cell transplantation (HCT), and any infection documented within 30 days prior to CAR T. Legend: IFD=invasive fungal disease; cHR= Crude hazard ratio; 95% CI= 95% Confidence interval; aHR= Adjusted hazard ratio; CAR T=Chimeric antigen receptor T cell therapy; HCT=autologous hematopoietic cell transplant; CRS=cytokine release syndrome; ICANS= immune effector cell-associated neurotoxicity syndrome; IEC-HS/MAS= immune effector cell-associated HLH-like syndrome/macrophage activation syndrome; ANC=absolute neutrophil count; ALC=absolute lymphocyte count. Note:* indicates the variable was treated as a time-dependent variable in the analysis. Multivariate analysis on mold infection was not performed due to the small number of the events. Conclusion IFD after CAR T for NHL is uncommon. Higher grade toxicities and their treatment, as well as prior HCT and prior infections, may identify those at highest risk. Additional studies are needed to individualize antifungal PPx strategies in this population. Disclosures Charles Gaulin, MBBS, ADC Therapeutics: Honoraria|DeciBio: Advisor/Consultant|Sanofi: Honoraria Roy F. Chemaly, MD/MPH, AiCuris: Advisor/Consultant|AiCuris: Grant/Research Support|Ansun Pharmaceuticals: Advisor/Consultant|Ansun Pharmaceuticals: Grant/Research Support|Astellas: Advisor/Consultant|Eurofins-Viracor: Grant/Research Support|InflaRX: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck/MSD: Advisor/Consultant|Merck/MSD: Grant/Research Support|Moderna: Advisor/Consultant|Oxford Immunotec: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Roche/Genentech: Advisor/Consultant|Roche/Genentech: Grant/Research Support|Shinogi: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Tether: Advisor/Consultant Fareed Khawaja, MBBS, Eurofins Viracor: Grant/Research Support|Symbio: Grant/Research Support

P-777. Assessment of Epidemiologic Case Definitions for Disseminated Nontuberculous Mycobacterial Disease in Patients Without AIDS

Abstract Background Disseminated Mycobacterium avium complex (MAC) infection rates have declined in persons with HIV; some studies report increasing numbers of disseminated nontuberculous mycobacteria (NTM) infections in other groups of immunocompromised persons. However, no consensus definition exists for disseminated NTM in these populations. We compared characteristics of disseminated NTM in persons without AIDS using different epidemiologic definitions.Table 1.Disseminated nontuberculous mycobacteria definitions.. Methods CDC’s Emerging Infections Program conducted active, laboratory- and population-based NTM surveillance in 4 states (11 counties) during 2021–2022 to identify patients with NTM in clinical specimens, excluding stool or rectal swabs. Clinical and laboratory data were collected via medical record review. Disseminated NTM definitions are shown in Table 1. We determined the numbers of patients without AIDS who met each definition. Among those meeting each definition we calculated the percentages of patients with: 1) selected immunocompromising conditions; 2) MAC infection; and 3) documented clinical diagnosis of any NTM infection (i.e., NTM not likely to represent contamination or colonization).Figure 1.Number of patients meeting each disseminated nontuberculous mycobacteria definition, Emerging Infection Program, 2021–2022 (N=59). Results Among 877 patients with NTM and without AIDS, 15 patients (1.7%) had a documented disseminated NTM clinical diagnosis (definition 1); 59 (6.7%) met ≥1 of the 3 definitions. Although more patients met definition 2 (31, 3.5%) or definition 3 (53, 6.0%) than definition 1, definition 2 only captured 10/15 (66.7%) patients with a documented disseminated NTM clinical diagnosis; definition 3 captured only 9/15 (60.0%) (Figure 1). The proportion of patients with malignancy, immunosuppressive medication, or transplant differed by definition as did the proportion infected with MAC. Seven of 31 patients meeting definition 2 (22.6%) and 14/53 (26.4%) patients meeting definition 3 did not have a clinician documented diagnosis of any NTM infection in the medical record (Figure 2).Figure 2.Proportion of patients with malignancy(a), immunosuppressive medication(b), transplant(c), isolation of M. avium complex, or clinical diagnosis of any type of nontuberculous mycobacteria infection(d), stratified by disseminated NTM definition, Emerging Infections Program, 2021–2022. Conclusion Each disseminated NTM definition identified a different group of patients, limiting their usefulness and comparability. Development of a standard epidemiologic definition for disseminated NTM in persons without AIDS will enable better understanding of disease impact in susceptible populations. Disclosures Kevin L. Winthrop, MD, MPH, AN2: Advisor/Consultant|AN2: Grant/Research Support|Insmed: Advisor/Consultant|Insmed: Grant/Research Support|Mannkind: Advisor/Consultant|Mannkind: Grant/Research Support|Paratek: Advisor/Consultant|Paratek: Grant/Research Support|Renovion: Advisor/Consultant|Renovion: Grant/Research Support|Spero: Advisor/Consultant|Spero: Grant/Research Support

P-21. Comparison of Three RSV Vaccine Lower Respiratory Tract Disease Primary Endpoint Definitions for Adult Vaccine

Abstract Background Despite their public health importance, a consensus definition for lower respiratory tract disease (LRTD), or illness (LRTI) is lacking. Clinical trials of three respiratory syncytial virus (RSV) vaccines for older adults used different LRTI/LRTD definitions for vaccine efficacy (VE). We hypothesize differences between definitions could bias product comparisons.Table 1.Variation of signs or symptoms included in criteria to meet case definition of LRTI or LRTD in three RSV vaccine clinical trials Methods We reviewed case definitions for LRTI/LRTD in RSV vaccine clinical trials conducted in older adults.Table 2.Specified values for symptoms/signs included in LRTI/LRTD criteria definitions for three RSV vaccine clinical trials Results Two of three published RSV vaccine clinical trials from Pfizer and Moderna used two outcomes (LRTI/LRTD with ≥2 signs/symptoms or ≥3 signs/symptoms) to measure VE, while the third trial from GlaxoSmithKline (GSK) used one (combining ≥2 and ≥3 signs/symptoms) (Table 1). The Pfizer trial included 5 signs/symptoms as components of LRTI; three of these (tachypnea, wheezing, shortness of breath) suggest lower airway involvement and two (cough and self-reported sputum production) could also result from upper airway infection. At interim analysis, 29 of 45 cases had only 2 symptoms (64.4%). Of these 29, 25 had only cough and sputum production (86.2%). The GSK trial, by contrast, required all LRTD cases to include at least one sign, all of which indicated lower airway involvement (Table 2). The Moderna trial included 10 signs/symptoms, including the potential for subjects to have only cough and sputum production. Even within signs/symptoms, definitions differed (e.g., tachypnea cutoff ranged from 20 to 25 breaths per minute; Table 2). When using comparable definitions, full season 1 VEs for Pfizer and GSK products were similar while the point estimate for the Pfizer product was higher during season 2 (Table 3).Table 3.Vaccine efficacy for three RSV vaccine clinical trials using study LRTI/LRTD definitions Conclusion Lack of standard case definitions limit ability to compare results across trials. Some ≥2 LRTI events for Pfizer and Moderna may not have involved the lower respiratory tract but rather the upper respiratory tract only. The most comparable case definitions likely are ≥3 signs/symptoms LRTI in the Pfizer and Moderna trials, and LRTD in the GSK trial. Disclosures Sarah E. Williams, MD, MPH, Pfizer, Inc: Salary|Pfizer, Inc: Stocks/Bonds (Private Company) Elizabeth Begier, MD, M.P.H., Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds (Private Company) Kumar Ilangovan, MD, MSPH, MMCi, Pfizer, Inc.: salary|Pfizer, Inc.: Stocks/Bonds (Public Company) Cassandra Hall-Murray, PharmD, Pfizer, Inc.: employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Bradford D. Gessner, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)

Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infections in Immunocompromised Patients: Literature Review and Proposed Definitions for Use in Clinical Trials.

Herpes simplex virus (HSV) infection is one of the most prevalent viral infections worldwide. In general, host immunity is sufficient to clear viral shedding and recurrences, although it is insufficient to prevent subsequent virologic reactivations. In immunocompromised patients, prolonged and difficult-to-treat HSV infections may develop. The diagnosis of refractory HSV infection is based on the lack of clinical response to nucleoside analogs. Antiviral resistance is confirmed via genotypic and/or phenotypic testing. To provide consensus definitions of refractory and/or resistant (R/R) HSV mucocutaneous infections for clinical trial use, the HSV Resistance Working Group of the Transplant Associated Viral Infections Forum, which includes international clinicians, scientists, industry representatives, and regulatory officials, conducted a literature review of previously published data related to R/R HSV infections in immunocompromised patients. We propose definitions of R/R HSV mucocutaneous infections, which will be subject to re-evaluation and revision based on forthcoming data and future studies.

A Comparison of Established Diagnostic Criteria for Cachexia and Their Impacts on Prognostication in Patients with Oesophagogastric Cancer

Background: Cachexia is common in patients with oesophagogastric cancer. The syndrome is characterised by tissue wasting (muscle and fat), anorexia, and reduced physical function, which result from complex interactions between the tumour and its host. Heterogeneity in the diagnostic criteria used for cachexia has hindered their clinical utilisation. This study aimed to compare the two established cachexia definitions (Fearon’s consensus definition and the Global Leadership Initiative on Malnutrition [GLIM] criteria) and their relationships with survival in patients with oesophagogastric cancer. Methods: Consecutive patients newly diagnosed with oesophagogastric cancer (January 2019 to December 2020) were identified from a prospective regional database. Involuntary weight loss, BMI, CT body composition analyses, and neutrophil–lymphocyte ratios were recorded at clinical staging. These data were used to assess patients for cachexia according to Fearon and GLIM diagnostic criteria. The primary outcome of interest was overall survival. Results: Overall, 465 patients (66.9% male, median 71 years) were diagnosed with oesophagogastric cancer during the 2-year study period. Cachectic proportions differed between definitions (Fearon: 59.1% vs. GLIM: 44.1%), and only 49.1% of the 322 patients who met one set of diagnostic criteria were cachectic according to both. Patients who met the GLIM criteria were significantly more comorbid and had a poorer performance status; however, no such difference was evident when using the Fearon definition. Those patients who met either set of diagnostic criteria had shorter survival than those who met neither (p &lt; 0.001). Following adjustment for confounders, GLIM-defined cachexia was more strongly associated with reduced survival (aHR: 1.57 [95% CI: 1.25–1.96], p &lt; 0.001) than Fearon-defined cachexia (aHR: 1.41 [95% CI: 1.13–1.76], p = 0.002). Patients who only met the Fearon diagnostic criteria had prolonged survival (median: 363 days) when compared to those who met only GLIM (median: 158 days) or both definitions (median: 120 days). A secondary analysis of those patients who met the GLIM diagnostic criteria (n = 205) compared the three potential phenotypical criteria used in this definition. Only reduced muscle mass, and not low BMI or weight loss, was associated with poorer survival (aHR: 1.88 [95% CI: 1.15–3.07], p = 0.012) in this group. Conclusions: Cancer cachexia is strongly associated with shortened survival in patients with oesophagogastric cancer. Classification using the GLIM criteria provides more effective prognostication and this definition should be utilised in multidisciplinary patient care.

Developing Teacher‐Leaders for Multilingual Students on the Mexico–United States Border

ABSTRACTThis brief describes how three school districts, one charter school system, a county office of education, and one institution of higher education collaborated to develop the leadership, equity, and access for languages (LEAL) professional development certificate for teacher‐leaders committed to serving multilingual learners on the Mexico–United States border. LEAL was designed and implemented using knowledge, dispositions, and skills for critically conscious pedagogy as the guiding framework to create consensus definitions of teacher‐leaders of multilingual students. Researchers reviewed and interpreted weekly meeting agendas, email correspondence, and the evaluation plan to define and use criteria for the selection of LEAL participants. Researchers implemented an innovative collaborative process of surveys, meetings, and goal‐setting with school district and charter school system administrators to identify current in‐service teachers that would exemplify commitment to serving multilingual learners in their schools and communities. This brief highlights the importance of interinstitutional partnerships for calibrating consistent definitions of teacher‐leaders as well as the value of creating customized seminars and conferences for collegial collaboration across local education agencies (LEAs).

P0378 Normalization or reduction of at least 50% in faecal calprotectin levels after 3 months of treatment predicts clinical and endoscopic remission at 1 year in patients with ulcerative colitis: results of the prospective MIROIR study

Abstract Background The STRIDE-2 consensus considers the improvement of faecal calprotectin (Fcal) (biochemical response) as an intermediate goal in ulcerative colitis (UC). However, no consensual definition of biochemical response is currently available. MIROIR study evaluated the performance of Fcal levels three months after initiating treatment to predict clinical and endoscopic remission at 12 months in UC. Methods In this prospective longitudinal prediction study, any adult UC patient with partial Mayo score (&amp;gt;2) and endoscopic Mayo score (MES) ≥2, requiring starting therapy for UC was included. Patients with acute severe colitis or prior colectomy were excluded. Clinical and biological data, including Fcal levels, were collected, at baseline, month 3 (M3), M6, M9, and M12. Endoscopic and histological (Nancy index) evaluations were performed at inclusion, 3 months, and 12 months. Physicians were blinded from Fcal levels. The primary endpoint was Fcal level at 3 months, while the primary dependent variable was therapeutic success defined as clinical remission (total Mayo score ≤ 2 with endoscopic Mayo score (MES) = 0 or 1) at M12, without dose escalation or treatment discontinuation due to failure. Results Among 62 included patients, the mean age at inclusion was 43.9 ± 14.4 years, with 55.5% being male. UC extent was proctitis (E1) in 13.7%, left-sided colitis (E2) in 39.2%, and pancolitis (E3) in 47.1%. At baseline, endoscopic activity was Mayo 2 and Mayo 3 in 46.3% and 53.7%, respectively. and median ffcal level was 665 µg/g [296-1800]. Initiated therapies were 5-ASA (13.0%), corticosteroids (13.0%), immunosuppressants (5.5%), anti-TNF agents (26.4%), vedolizumab (22.6%), ustekinumab (35.8%), and tofacitinib (3.7%). At M3, 10 patients (18.5%) achieved endoscopic remission (MES 0), 23 (42.6%) showed endoscopic improvement (MES 0 or 1), while 10 (18.5%) and 13 (24.1%) still had endoscopic activity, MES 2 or 3, respectively. The median Fcal level at M3 correlated with MES at M3: 27 [14-142], 115 [20-460], 665 [135-1830], 755 [472-1340] (p = 0.0006) for MES 0, 1, 2 and 3, respectively, and with endoscopic activity (MES ≥2) at M3 (90 [18-192] vs. 679 [428-1830], p = 0.0001) with a substantial effect size (1.32 [0.72-1.91]). Fcal level &amp;lt;150 µg/g at M3 was the best threshold to predict therapeutic success at M12. A decrease of at least 50% in Fcal level at M3 was the best threshold for predicting therapeutic success at M12, with high negative predictive value: 92.3%[74.9% - 99.1%]. Conclusion Our study demonstrates that normalization or reduction of at least 50% in Fcal level after 3 months of treatment predicts therapeutic success at 1 year in ulcerative colitis. This could therefore be proposed as a definition of biochemical response.

Bacillus Calmette-Guerin (BCG) infections following intravesical BCG immunotherapy: a systematic review protocol

BackgroundAlthough intravesical Bacillus Calmette-Guerin (BCG) immunotherapy usually exhibits a favorable safety profile, it can lead to the development of BCG infections, both localized and disseminated. Understanding of BCG infections following intravesical BCG immunotherapy is limited because of the lack of consensus definitions of BCG infections and limited post-instillation follow-up. We aim to perform a systematic review of the literature of BCG infections following intravesical BCG immunotherapy to elucidate the epidemiology, risk factors, and outcomes of BCG infections.MethodsSystematic review of peer-reviewed published articles that describe the treatment of one or more persons with intravesical BCG and the occurrence of BCG infections among these patients. No temporal, geographic, or demographic limitations will be applied. Animal studies will be excluded. Gray literature, editorials, and comments will be excluded. Information sources will include the following databases: MEDLINE, Embase, and Web of Science. A search concept representing BCG and intravesical administration will be applied after validation against a set of pre-selected articles. Screening and data extraction will be performed in duplicate by two independent reviewers. Disagreements will be resolved by a third independent reviewer. The methodological quality of studies will be assessed using the Mixed Methods Appraisal Tool. A narrative synthesis of the extracted data will be provided in line with the guidance from the Centre for Reviews and Dissemination. The quality of evidence for all outcomes will be judged using the Grading of Recommendations Assessment, Development, and Evaluation working group methodology.DiscussionThe data generated by this review will assist clinicians in managing BCG-infected patients and inform future research efforts.Systematic review registrationIn accordance with international guidelines, our systematic review protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) on February 26, 2024.

P0868 Long term outcomes from UK mesenchymal stem cell therapy for perianal fistulising Crohn’s disease: a 5 Year follow up

Abstract Background Perianal fistulising Crohn’s disease (pfCD) is a debilitating and complex complication of Crohn’s disease that is challenging to manage and associated with poor long-term outcomes. Mesenchymal stem cell (MSC) therapy has emerged as a promising treatment option for medically refractory pfCD, but long-term data on efficacy and safety are limited. This study investigates the long-term outcomes of MSC therapy in patients with pfCD, focusing on clinical, radiological and patient-reported outcomes. Methods All patients treated with a single dose of MSC therapy at two tertiary referral centres in the UK were included in a prospectively maintained cohort and patients were followed up for 5 years. The primary outcomes were clinical and radiological response, assessed using the fistula drainage assessment, TOpClass consensus definitions of radiological improvement and healed fistulae, MRI-based activity indices and expert radiologists’ VAS (Visual Analogue Scale) score of disease severity. Secondary outcomes include the Perianal Disease Activity Index (PDAI) and the Vaizey incontinence score. Results The analysis included 24 patients (14 female, 10 male) with a mean age of 37. The median follow-up was 60 months (clinical assessments) and 54 months (radiological evaluations). At 5 years, 25% patients (6/24) had evidence of persisting clinical response, and 54.2% (13/24) were in clinical remission. Radiologically, 75% (18/24) of patients showed improvement in the first 12 months post-treatment, with 37.5% (9/24) maintaining long-term radiological improvement at 5 years. Four patients (16.7%) achieved complete radiological healing at 5 years. The Van Assche Index score improved post treatment (p = 0.042) and long-term (p = 0.019), in concordance with a reduction in the radiologists’ VAS severity score post – treatment (p = 0.009) and at 5 years (p = 0.043). Significant reductions in PDAI were observed from baseline to 18 months (p&amp;lt; 0.001) and 5 years (p= 0.002). During the 5-year follow-up period, 58.3% (14 out of 24) of patients did not require additional surgery, and no adverse events or long-term continence impairment were observed (p = 0.582). Conclusion This study demonstrates that MSC therapy for pCD results in significant long-term clinical and radiological improvements, with clinical remission in half of patients at 5 years and a safety profile consistent with prior studies. Despite the clinical remission, at 5 years only a minority experienced sustained radiological healing (16.7%) according to the new and stringent TOpClass definition. These findings support the use of MSC therapy as an effective treatment for pfCD, with durable benefits in symptom control and quality of life.

The prebiotic landscape: history, health and physiological benefits, and regulatory challenges - an IPA perspective part 1.

Prebiotics are becoming increasingly recognized by consumers, health care professionals and regulators as important contributors to health. Nonetheless, the development, progress, and adoption of prebiotics is hindered by loose terminology, various misconceptions about sources and types of compounds that may be classified as prebiotics, and the lack of consensus on a definition that satisfies regulators. Evolving knowledge of the microbiome and its effects on host health has generated opportunities for modulation of the microbiota that can support host health. Various types of biotics - probiotics, prebiotics, and postbiotics, are compounds that either modulate the microbiota or arise from the microbiota, affecting health locally and distally. Each of these classes of biotic compounds have distinct, yet complementary benefits. While many scientists have proposed definitions for prebiotics, and there have been attempts by selected scientists to develop a 'consensus definition', the fact remains that globally, scientists, manufacturers, and marketers have adopted different definitions to suit their own interests and purposes, leading to confusion among consumers and health care professionals. The pathway to regulatory acceptance and to reduce/eliminate confusion is a definition that puts the focus on the consumer, and the benefits that consumers can realise from consumption of prebiotics. This consumer-focused approach, supported by science, will also align with regulators and support broader regulatory approval of prebiotics as a category. In this review, we discuss the history of prebiotics, and introduce criteria and a decision tree to classify compounds as prebiotics, supported by the scientific literature to date. This includes a summary of compounds that have been clearly recognised as prebiotics. We also review the microbiota, microbiome, and the various ways in which prebiotics can beneficially affect the microbiota and health. The safety and efficacy of prebiotics is also reviewed, along with effective doses and limitations associated with prebiotic use. This includes scientific tools and methods that help to establish the function, safe use and efficacy of a prebiotic. We also identify misconceptions that can be addressed in communications to consumers and health care professionals. Manufacturing guidelines and the current regulatory status of prebiotics in various jurisdictions are also reviewed. Collectively, this review provides an in-depth overview of the role for prebiotics to support the health of consumers. This consumer-focused approach provides clear criteria for the product category, safe use, effective communication of health benefits and limitations, and a pathway towards regulatory approval.

Standardisation of the radiological definition of supramaximal resection in glioblastoma.

Glioblastoma remains the most common and lethal primary malignant brain tumour, with high rates of recurrence and progression despite gross-total resection of the contrast-enhancing region based on T1-weighted MRI. There has been growing interest in exploring "supramaximal" resections that extend beyond contrast-enhancing borders, with initial retrospective data suggesting survival benefit, but there is currently no consensus definition. In this systematic review, we explore the evolution of supramaximal resection in glioblastoma, dissect the incongruencies in the literature regarding its definition, qualitatively appraise each definition and discuss the results of various studies that have explored its impacts on patient outcomes. MEDLINE, EMBASE, SCOPUS, Cochrane Registry of Clinical Trials and Pub-MED were systematically searched for studies of glioblastoma patients who had undergone supramaximal resection. After screening and applying eligibility criteria, 25 studies were included in the final review. Definitions were grouped according to radiological modality and visualisation adjuncts and included various extents of resection of hyperintensity visualised using T2-Fluid-Attenuated Inversion Recovery, various volumetric resections of the non-contrast enhancing region, removal of methionine-uptake areas on PET, complete removal of 5-aminolevulinic acid fluorescent tissue and lobectomies. Our systematic review identified a general trend suggesting a survival benefit from supramaximal resection compared to gross-total resection but, more importantly, demonstrated the limitations of these studies due to selection bias and substantial methodological heterogeneity. Ultimately, our findings demonstrate the need for an applicable, standardised and specific definition for supramaximal resection so that prospective studies can determine prognostically significant clinical data to guide the surgical management of glioblastoma.

Imaging and management of calcium pyrophosphate deposition disease.

The radiological manifestations of calcium pyrophosphate deposition (CPPD) revolve around two main axes: the asymptomatic form and CPPD disease. The latter is a consequence of an immune response to calcium phosphate crystals. Chondrocalcinosis is broadly considered the radiographic manifestation of CPPD regardless of whether it is asymptomatic or associated with inflammatory arthritis. CPPD is associated with osteoarthritis although the direction of such association is still unclear. Apart from the detection of CPP crystals in synovial fluid, imaging (mainly conventional radiography and increasingly ultrasound) plays a central role in the diagnosis of CPPD disease. Recently, CT has been added as a diagnostic tool, especially in deep anatomic locations such as crowned dens. To date, no treatment is effective in dissolving CPP crystals. For now, the focus of current treatment strategies remains inflammation control. Our aim is to review the epidemiology, pathogenesis, and clinical and imaging manifestations of asymptomatic and symptomatic CPPD. We will also discuss recent consensus definitions and classifications of CPPD disease.

A Simple Endoscopic Score for Crohn's Disease (SES-CD) ≥ 7 Predicts Disease Progression.

Up to 30% of patients with Crohn's disease (CD) will experience a mild disease course. However, there is no consensus definition for mild CD. To examine the Simple Endoscopic Score for Crohn's disease (SES-CD) thresholds best associated with low likelihood of long-term disease progression. We conducted a multicentre retrospective cohort study at three tertiary care centres in United States and Europe. We analysed data from 177 surgery-naïve patients with CD who had endoscopic assessment while not on immunosuppressive therapy. The primary outcome was disease progression (systemic steroids, biologic or immunomodulator therapy initiation; new stricturing or penetrating complications; or CD-related hospitalisation or surgery). Univariable and multivariable Cox proportional hazards modelling identified predictors of the primary outcome at 2 and 5 years following endoscopy. Disease progression occurred in 23% and 35% of patients at years two and five, respectively. Endoscopic severity at enrolment independently predicted disease progression. Compared to those with an SES-CD of 0, an SES-CD ≥ 7 had a greater risk of progression at 2 years (HR 2.50, 95% CI 1.09-5.72) and 5 years (HR 2.89, 95% CI 1.41-5.91). SES-CD > 7 remained independently predictive of disease progression among the 129 immunosuppression-naïve patients (HR 5.65, 95% CI 1.49-21.52) and after excluding patients with prior penetrating disease (HR 2.32, 95% CI 1.00-5.45). SES-CD ≥ 7 predicts disease progression in mild CD. A score ≤ 6 may help identify patients less likely to progress and be part of the definition of mild CD.