Nationwide Multicenter Study Research Articles

690. Analysis of high-risk antibiotics for Clostridioides difficile infections in Korean hospitals: A nationwide multi-center study

Abstract Background Clostridioides difficile infection (CDI) is a representative healthcare-associated infection, and the incidence rate continues to increase in Korea. The purpose of this study is to identify antibiotics that are highly related to CDI incidence in Korean hospitals. Methods From January-December 2019, all antibiotic prescription records, CDI test results, and a daily number of hospitalized patients were retrospectively collected from 10 university-affiliated hospitals in Korea. To exclude duplication, CDI tests that were conducted within 10 days after conducting previous CDI tests were excluded. When a positive result was detected from C. difficile toxin assay or PCR tests, we considered it as CDI. Antibiotics were defined as drugs corresponding to J01 in the WHO ATC classification, excluding anti-tuberculosis drugs, anti-parasitic drugs, antiviral drugs, and local antibiotics. The antibiotic usage was calculated as Days of Therapy (DOT). The CDI incidence rate and antibiotic usage were collected on a weekly basis and then corrected to 1,000 patient days. The correlation between CDI incidence rate and antibiotic usage was analyzed using the cross-correlation function test. Results CDI incidence and total antibiotic usage in each hospital ranged from 0.49-1.58/1,000 patient-days and 588.7-1000.4 DOT/1,000 patient-days, respectively. Cross-correlation function test shows that antibiotics that are highly related to CDI incidence were 2nd generation cephalosporin that was prescribed 6 weeks prior to CDI event (coefficient 0.320, P = 0.021), 4th generation cephalosporin that was prescribed 1 week prior to CDI event (coefficient 0.307, P = 0.027), and beta-lactam/beta-lactamase inhibitors (with anti-pseudomonal effects) that was prescribed 1 week prior to CDI event (coefficient 0.272, P = 0.050), lincosamide that was prescribed 2 weeks prior to CDI event (coefficient 0.278, P = 0.045), and oxazolidinone that was prescribed 8 weeks prior to CDI event (coefficient 0.362, P = 0.008). Cross-correlation coefficients between Clostridioides difficile infection incidence and antibiotic usage Conclusion Antibiotics highly associated with CDI incidence in Korean hospitals were second-generation cephalosporin, fourth-generation cephalosporin, beta-lactam/beta-lactamase inhibitors (with anti-pseudomonal effects), lincosamide, and oxazolidinone. Disclosures All Authors: No reported disclosures

Relevant adverse events and drug discontinuation of sacubitril/valsartan in a real-world Japanese cohort: REVIEW-HF registry

BackgroundThe characteristics, tolerability, and outcomes in patients with heart failure (HF) who are treated with sacubitril/valsartan remain unclear in Japan. MethodsWe conducted a nationwide multicenter study to evaluate the features and outcomes of patients newly prescribed sacubitril/valsartan for the management of HF. We analyzed adverse events (AEs) related to sacubitril/valsartan at 3 months, which were defined as hypotension, worsening renal function, hyperkalemia, and angioedema. Additionally, the association between AEs and outcomes was examined. ResultsAmong 993 patients, the mean age was 70 years and 291 (29.3 %) were female, and 22.8 % had left ventricular ejection fraction ≥50 %. Of them, 20.8 % had systolic blood pressure (sBP) <100 mmHg, and 19.5 % had estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 at baseline, which were the populations excluded from the eligibility in landmark trials. AEs related to sacubitril/valsartan were observed in 22.5 % of the patients at 3 months. Overall, 22.6 % of patients discontinued sacubitril/valsartan, and hypotension was the most common event leading to drug discontinuation. After adjustment, patients who had worse HF symptoms (New York Heart Association III or IV), sBP <100 mmHg, and eGFR <30 ml/min/1.73 m2 were associated with a higher risk of AEs related to sacubitril/valsartan. Additionally, patients experiencing AEs had a higher risk of cardiovascular death or HF hospitalization than those who did not. ConclusionIn Japan, sacubitril/valsartan was also prescribed to patients not eligible for landmark trials, and AEs were observed at a relatively high rate from soon after treatment initiation. Physicians should closely monitor patients for these events, especially in patients anticipated to have a higher risk of AEs.

Hangman's Fracture in Geriatric Population: A Nationwide Multicenter Study in Japan.

Retrospective multicenter study. To investigate the treatments of the geriatric population with hangman's fractures using a multicenter database under the Japan Association of Spine Surgeons with Ambition (JASA). The multicenter database included data from 1512 patients. We employed the Levine and Edwards classification for categorizing hangman's fractures. The study incorporated epidemiological data, including the prevalence of hangman's fractures, patient age, and follow-up duration. Bony fusion rates and length of hospitalization were recorded for Type I and Type II fractures, and the degree of neurological impairment was assessed. Hangman's fractures represented 62 cases, accounting for 7.4% of all cervical spine injuries. The patients had an average age of 76.6 ± 6.5years, and the mean duration of follow-up was 21.5 ± 23.6months. The study found that the bony fusion rate for hangman's fractures in the geriatric population was 88.9%. Surgical treatment was associated with a shorter hospitalization period for Type II fractures compared to conservative treatment. Thirteen cases of hangman's fractures in the geriatric population, accounting for 21%, were complicated by spinal cord injury. This is the largest study to date on hangman's fractures in geriatric population ≥65years. Type I and Type II fractures, according to the Levine and Edwards classification, had a bony fusion rate of up to 90%. In patients with Type II fractures, surgical treatment led to a shorter initial hospital stay. Geriatric patients are at risk of spinal cord injury due to hangman's fractures.

In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan

BackgroundExtracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score.MethodsThis was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model.ResultsOf 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38–2.25] for shockable rhythm and 5.37 [95%CI 2.53–11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82–1.49] for shockable rhythm and 4.25 [95%CI 1.43–12.63] for non-shockable rhythm, compared to controls.ConclusionECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.Graphical

Abstract 12720: A Nationwide Multi Center Study From China, Comparing Long-Term and Standard Cardiopulmonary Resuscitation: Epidemiology, Risk Factors, and Outcomes

Introduction: The association between the duration of cardiopulmonary resuscitation (CPR) and patient outcomes remains largely unknown. Hypothesis: long-term CPR (LCPR) may benefit certain group of patients. Methods: In this retrospective cohort study, data from the Chinese Emergency Triage Assessment and Treatment database 1.0 (CETAT 1.0) were utilized. The study included CA patients admitted to 14 teaching hospitals in 7 provinces between July 2015 and July 2020. Patients were categorized into SCPR and LCPR groups based on the duration of resuscitation, where SCPR referred to CPR duration less than 60 mins, and LCPR referred to CPR duration equal to or more than 60 mins. The primary outcome measured was ROSC rates between the two groups, while the secondary and tertiary outcomes was 24-hour and 7-day survival rates. A multivariate logistic regression model was employed to analyze the factors influencing ROSC between groups. Results: A total of 529 patients were enrolled in the study, with 372 in the SCPR group and 157 in the LCPR group. Among them, 126 (33.9%) patients in the SCPR group and 56 (35.7%) in the LCPR group achieved ROSC without statistically difference between groups. Furthermore, 31 patients (8.3%) in the SCPR group and 7 patients (4.5%) in the LCPR group survived at 24 hours, while 13 patients (3.5%) in SCPR and 4 patients (2.5%) in LCPR group survived at 7 days, both without statistical difference. Factors associated with SCPR operation included Lower BMI, previous hypertension, daytime admission, hands-only compression, and ventilation. SpO2 and P ET CO2 were independent factors associated with ROSC, Moreover, in both groups higher SpO2 and P ET CO2 levels were associated with a higher rate of ROSC, suggesting that for this specific patient cohort, longer duration of CPR should be considered. Conclusions: Longer duration of CPR may need to be emphasize for certain group of patients, particularly those with high SpO2 and PET CO2 during CPR.

Abstract 17538: The Weekend Effect on In-Hospital Outcomes of Elderly Patients With Acute Ischemic Stroke and Concurrent COVID-19 Infection: A Nationwide Multicenter Study

Background: Acute ischemic stroke (AIS) and COVID-19 are individually associated with poor outcomes. The impact of the pandemic on the US healthcare system, including staff shortages and disparities, may have delayed timely interventions and adherence to guidelines. We investigated the Weekend Effect on outcomes in elderly patients with AIS and COVID-19 to better understand its relationship during the challenging pandemic period. Methods: Using ICD-10-CM codes, we analyzed AIS and COVID-19 hospitalizations among the elderly (&gt;65 years) from the 2020 National Inpatient Sample. Weekday and weekend admissions were compared for baseline characteristics, comorbidities, and outcomes. The multivariable analysis was adjusted for confounding variables. A two-tailed p&lt;0.05 was considered significant. Results: Of 14,070 total AIS and concurrent COVID-19 admissions among the elderly, 10,425 were on weekdays, and 3645 were on weekends. While both cohorts exhibited comparable age distributions, the weekend admissions had a higher percentage of females (47.1% vs. 45.2%) and whites (59.5% vs. 58.1%). They had a higher prevalence of hypertension (82.2% vs. 78.6%), hyperlipidemia (52.9% vs. 50.1%), chronic pulmonary disease (19.1% vs. 17%), obesity (15% vs. 13.6%), depression (10.2% vs. 8.2%). Additionally, all-cause mortality (33.5% vs. 32.5%) and cardiogenic shock (1.9% vs. 1.7%) were slightly higher among weekend admissions. Upon adjusting for confounding factors, the overall mortality rate among weekend admissions showed no significant association, aOR-1.15 [95%CI:0.42-0.96; p-0.169]. Conclusion: Although there is a higher prevalence of comorbidities and overall mortality among weekend admissions, no significant association between the Weekend Effect and poor in-hospital outcomes in elderly COVID-19 patients with AIS was noted. However, ensuring adequate staffing and resource availability during weekends may enhance the quality of care provided.

PAUSATE Study: Prevalence and appropriateness of the use of antimicrobials in Spanish hospitals

ObjectiveTo determine the prevalence and appropriateness of antimicrobial use in Spanish hospitals through a pharmacist-led systematic cross-sectional review. MethodA nationwide multicenter cross-sectional study was conducted on 10% of the patients admitted to the participating hospitals on one day in April 2021. Hospital participation was voluntary, and the population was randomly selected. The study sample was made up of patients who, on the day of the study, received at least one antimicrobial belonging to groups J01, J02, J04, J05AB, J05AD or J05AH in the Anatomical Therapeutic Chemical Classification System. The pharmacist in charge made a record and carried out an evaluation of the appropriateness of antimicrobial use following a method proposed and validated by the Pharmaceutical Care of Patients with Infectious Diseases Working Group of the Spanish Society of Hospital Pharmacy. The evaluation method considered each of the items comprising antimicrobial prescriptions. An algorithm was used to assess prescriptions as appropriate, suboptimal, inappropriate and unevaluable. ResultsOne-hundred three hospitals participated in the study and the treatment of 3,568 patients was reviewed. A total of 1,498 (42.0%) patients received antimicrobial therapy, 424 (28.3%) of them in combination therapy. The most commonly prescribed antimicrobials were amoxicillin-clavulanic acid (7.2%), ceftriaxone (6.4%), piperacillin-tazobactam (5.8%), and meropenem 4.0%. As regards appropriateness, prescriptions were considered appropriate in 34% of cases, suboptimal in 45%, inappropriate in 19% and unevaluable in 2%. The items that most influenced the assessment of a prescription as suboptimal were completeness of medical record entries, choice of agent, duration of treatment and monitoring of efficacy and safety. The item that most influences the assessment of a prescription as inappropriate was the indication of antimicrobial agent. ConclusionsThe method used provided information on the prevalence and appropriateness of the use of antimicrobials, a preliminary step in the design and implementation of actions aimed at measuring the impact of the use of antimicrobials within the antimicrobial stewardship programs.

Clinical Characteristics and Outcomes of Myeloid Neoplasms with Mecom Rearrangement: Results from a Nationwide Multicenter Study

MECOM rearrangements are detected in myeloid neoplasms [myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML)] which are associated with dismal prognosis. Classic MECOM rearrangements include inv(3)(q21q26.2) and t(3;3)(q21;q26) while non-classic subtypes are 3q26.2/ MECOM rearrangement with other partners. Both classic and non-classic rearrangements result in MECOM overexpression which involves in the process of leukemogenesis. Recently, the World Health Organization classification 2022 categorized myeloid neoplasms with these genetic abnormalities as “AML with MECOM rearrangement” regardless of blast count. We aim to explore frequency, clinical characteristics and outcomes including treatment response in this AML subtype among Thai myeloid neoplasms. AML data was collected from a national registry which were conducted by Thai acute leukemia working group. Other than AML with MECOM rearrangements, AML was categorized as favorable, intermediate, and adverse risk groups according to European Leukemia Network 2022. MDS data was collected from a multicenter study group involving 4 medical centers. Other than MDS with MECOM rearrangements, MDS was categorized into 5 risk groups according to R-IPSS score system (very low, low, intermediate, high and very high-risk groups). Myeloid neoplasms with MECOM rearrangements were analyzed among their diseases and grouped together and compared to MDS and AML cohorts. A total of 9 cases of myeloid neoplasms with MECOM rearrangement were detected. Among non-M3 AML cases, there were 6 cases with MECOM rearrangement from 746 non-M3 AML (0.8%) while 3 cases were detected in 163 MDS (1.8%). Seven of 9 cases (78%) were female gender. Five of 9 cases were classic MECOM rearrangement [1 case with inv(3)(q21q26.2) and 4 cases with t(3;3)(q21;q26)] while the other 4 cases were non-classic rearrangements [3 cases with t(3;21)(q26.2;q22) and 1 case with t(3;7)(q26;q21)]. In the AML cohort, AML with MECOM rearrangement showed lower white blood cell, but higher platelet counts compared to other groups (favorable, intermediate, and adverse risk groups) ( Table 1). Among AML cases receiving intensive chemotherapy, MECOM rearrangement subgroup showed lower complete response (CR) rate compared to others favorable, intermediate, and adverse risk groups. (0% vs. 77.3% vs. 37.6% vs. 23.8%; p&amp;lt;0.001). Of note, among 6 AML with MECOM rearrangement, there were 4 patients who received intensive chemotherapy but none of them responded to the treatment. In the MDS cohort, MDS with MECOM rearrangement showed lower hemoglobin and platelet counts compared to other groups ( Table 2). Among 3 MDS with MECOM rearrangement, one patient received azacitidine with investigational drug (sabatolimab/placebo) and achieved complete hematologic response. He eventually progressed after 12 cycles of the treatments and subsequently died. When combining 3 MDS and 6 AML with MECOM rearrangement as one group and compared survival rate with others: survival rate of 9 myeloid neoplasms with MECOM rearrangementis worse than the adverse group of AML and the very high risk group MDS with a 1-year survival rate of 22% ( Figure 1 and 2). In conclusion, myeloid neoplasms with MECOM rearrangements are rare with the frequency of 0.8% in non-M3 AML and 1.8% in MDS. This subtype is more common in female gender. The prognosis of myeloid neoplasms with MECOM rearrangement is dismal with a 1-year survival rate of 16.7% in AML and 6-month survival rate of 33% in MDS. Chemotherapy should be avoided in this subtype due to non-responsiveness, hypomethylating agent showed benefit and can be considered as a bridging treatment before stem cell transplantation. Novel therapy targeting MECOM gene should be further explored to improve outcomes in this AML subtype.

A Prediction Model for Early Recurrence after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with CMML: A Nationwide Representative Multicenter Study

Introduction: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy. Some patients experience prolonged remission after aggressive chemotherapy, but the only current therapy with proven curative potential is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, not all CMML patients benefit from allo-HSCT, and many experience relapse. Relapse is the leading cause of treatment failure for CMML treated with allo-HSCT, and treatment options for patients relapsing after allo-HSCT are limited. This study conducted a nationwide multicenter real-world study to identify risk factors and develop a novel prediction model for early recurrence in CMML patient posttransplantation. Clinicians can improve the survival of CMML patients with a high risk of early recurrence by intervening as early as possible. Methods: Patients ≥18 years old with CMML treated with allo-HSCT for the first time between 2005 and 2022 were included in this nationwide, multicenter, real-world study. Twenty-seven medical centers participated in this analysis, including the derivation cohort from 26 centers and the validation cohort from another center. Information collected included demographic and clinical characteristics, previous treatments and responses, and allo-HSCT treatment details. We first calculated the univariable association of each variable with 1-year relapse in the derivation cohort. Second, the variables with p values less than 0.1 in the univariate analysis were further included as candidate predictors in the multivariate analysis using a backward stepwise logistic regression model. The variables that remained in the final model based on the outcomes of the multivariate analysis in the derivation cohort were identified as independent prognostic factors. A scoring system to predict early recurrence after allo-HSCT was also established, and scores were assigned to the prognostic factors based on the regression coefficient. Results: Using multivariable logistic regression methods with stepwise variable selection, two highly significant independent prognostic factors for the early recurrence of CMML posttransplantation were identified: bone marrow blast cell count at diagnosis (p=0.026; odds ratio [OR], 1.149; 95% confidence interval [CI], 1.02-1.30), and leukocyte count pretransplantation (p=0.005; odds ratio [OR], 1.212; 95% confidence interval [CI], 1.06-1.39). A risk grading model was constructed according to the regression coefficients. Bone marrow blast cell count 0-5% is 0 point, 5%-10% is 1 point; 10-20% is 2 points, and &amp;gt;20% is 3 points. Leukocyte count 0-10×10 9/L is 0 point, 10-20×10 9/L is 2 points, and &amp;gt;20 ×10 9/L is 4 points. The points scored for each of these two factors were added to yield the overall risk score, which ranged from zero to seven. Patients were stratified into a low-risk group (0-1 point), a intermediate-risk group (2-3 points) and a high-risk group (4-7 points). The validated internal c-statistic was 0.790 (95% CI, 0.657-0.923), and the external c-statistic was 0.710 (95% CI, 0.580-0.840). The early recurrence rates of the derivation cohort in the low-risk, intermediate-risk, and high-risk groups were 5.9%, 17.9% and 31.8% (p&amp;lt;0.05). The Kaplan‒Meier estimations of relapse-free survival revealed good separation between these risk groups, and 91.9%, 79.4% and 66.1% (p&amp;lt;0.05), respectively. According to the calibration plots, the model-predicted probabilities showed a good correlation with the actual observed frequencies. Decision curve analysis indicated that the clinical implementation of the prognostic model could benefit early recurrence CMML patients. Conclusion: CMML patients who relapse after allo-HSCT have a poor prognosis. An integrated prediction model based on clinical biomarkers was developed and externally validated, and this is the first straightforward scoring model that incorporates clinical and laboratory risk factors to evaluate the early recurrence of CMML patients after receiving allo-HSCT. This model can be effectively utilized to help improve the survival and prognosis of CMML patients by accelerating the early identification of patients at a high risk of relapse and contributing to the appropriate implementation of urgent medical support.

Time to extend the indication for sentinel node biopsy in vulvar cancer? Results from a prospective nationwide Swedish study

ObjectiveTo assess detection rates and negative predictive values of sentinel node biopsy in vulvar squamous cell carcinoma with tumors ≥4 cm, multifocal tumors, and in locally recurrent disease.MethodsBetween December 2019...

Mortality risks from a spectrum of causes associated with sand and dust storms in China

Sand and Dust Storms (SDS) pose considerable health risks worldwide. Previous studies only indicated risk of SDS on overall mortality. This nationwide multicenter time-series study aimed to examine SDS-associated mortality risks extensively. We analyzed 1,495,724 deaths and 2024 SDS events from 1 February to 31 May (2013–2018) in 214 Chinese counties. The excess mortality risks associated with SDS were 7.49% (95% CI: 3.12–12.05%), 5.40% (1.25–9.73%), 4.05% (0.41–7.83%), 3.45% (0.34–6.66%), 3.37% (0.28–6.55%), 3.33% (0.07–6.70%), 8.90% (4.96–12.98%), 12.51% (6.31–19.08%), and 11.55% (5.55–17.89%) for ischemic stroke, intracerebral hemorrhagic stroke, hypertensive heart disease, myocardial infarction, acute myocardial infarction, acute ischemic heart disease, respiratory disease, chronic lower respiratory disease, and chronic obstructive pulmonary disease (COPD), respectively. SDS had significantly added effects on ischemic stroke, chronic lower respiratory disease, and COPD mortality. Our results suggest the need to implement public health policy against SDS.

Associations of corticosteroid therapy and tonsillectomy with kidney survival in a multicenter prospective study for IgA nephropathy

Efficacy of systemic corticosteroid therapy (CS) for long-term kidney survival in patients with IgA nephropathy (IgAN) is controversial. Therefore, prospective studies evaluating targeted therapies to lymphatic tissues in mucosal immune system responsible for production of nephritogenic IgA have been desired worldwide. Here, we aimed to evaluate the associations of CS and combination therapy of CS and tonsillectomy (CS + Tx) with kidney survival, using database from a nationwide multicenter prospective cohort study on IgAN. Primary outcome was a 50% increase in serum creatinine from baseline or dialysis induction. The analysis included 941 patients (CS/CS + Tx/non-CS 239/364/338), 85 (9.0%) of whom reached outcomes during median follow-up of 5.5 (interquartile range 2.0–8.0) years. On overlap weighting analysis with balanced baseline characteristics, CS and CS + Tx were associated with lower risk of kidney events when compared with non-CS (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.29–0.88 and HR 0.20, 95%CI 0.09–0.44, respectively). Notably, when compared with the CS, CS + Tx was associated with a lower risk of kidney events (HR 0.40, 95%CI 0.18–0.91). Present study demonstrated, keeping with favorable association of systemic CS with kidney survival, concurrent tonsillectomy as one of targeted interventions to lymphatic tissues may provide additional improvement to kidney survival in patients with IgAN.

Acute pancreatitis in Turkey: Results of a nationwide multicenter study

BackgroundAcute pancreatitis (AP) is the most common gastrointestinal disease requiring hospitalization, with significant mortality and morbidity. We aimed to evaluate the clinical characteristics of AP and physicians’ compliance with international guidelines during its management. MethodsAll patients with AP who were hospitalized at 17 tertiary centers in Turkey between April and October 2022 were evaluated in a prospective cohort study. Patients with insufficient data, COVID-19 and those aged below 18 years were excluded. The definitions were based on the 2012 revised Atlanta criteria. ResultsThe study included 2144 patients (median age:58, 52 % female). The most common etiologies were biliary (n = 1438, 67.1 %), idiopathic (n = 259, 12 %), hypertriglyceridemia (n = 128, 6 %) and alcohol (n = 90, 4.2 %). Disease severity was mild in 1567 (73.1 %), moderate in 521 (24.3 %), and severe in 58 (2.6 %) patients. Morphology was necrotizing in 4.7 % of the patients. The overall mortality rate was 1.6 %. PASS and BISAP had the highest accuracy in predicting severe pancreatitis on admission (AUC:0.85 and 0.81, respectively). CT was performed in 61 % of the patients, with the majority (90 %) being within 72 h after admission. Prophylactic NSAIDs were not administered in 44 % of the patients with post-ERCP pancreatitis (n = 86). Antibiotics were administered to 53.7 % of the patients, and 38 % of those received them prophylactically. ConclusionsThis prospective study provides an extensive report on clinical characteristics, management and outcomes of AP in real-world practice. Mortality remains high in severe cases and physicians’ adherence to guidelines during management of the disease needs improvement in some aspects.

Efficacy of cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn's disease-Aprospective nationwide multicenter cohort study.

The use of mesenchymal stem cells is considered anovel and promising therapeutic option for patients with perianal fistulizing Crohn's disease; however, data on its clinical application remain scarce. This multicenter nationwide study aimed to assess the clinical efficacy of mesenchymal stem cells in closing complex anal fistulas. In this study 14 Crohn's disease patients (3males, 11females) with complex anal fistulas treated in 3 tertiary hospitals in Austria were included between October 2018 and April 2021. Injection of 120 million allogeneic expanded adipose-derived mesenchymal stem cells (Cx601-darvadstrocel) was performed in each patient. Closure of the external fistula opening without secretion by external manual compression was defined as treatment success. The median age of the patient population at the time of surgery was 32years (range 26-53years) with amedian body mass index of 21.7 kg/m2 (range 16.7-26.6 kg/m2). Of the patients 12 (86%) received monoclonal antibodies (infliximab, adalimumab, ustekinumab, vedolizumab) at the time of surgery. The median number of complex fistulas was 1.4 (range 1-2), The median operative time was 20 min (range 6-50 min) with no perioperative complications. After amedian follow-up of 92weeks, we found successful fistula closure in 57.1% (n = 8) of treated patients. The perianal disease activity index did not improve significantly from initially 7 to amedian of 6 after 52weeks (p = 0.495). Darvadstrocel is asafe, minimally invasive surgical technique without significant perioperative complications. Clinical success can be expected in about half of the treated patients.

Diagnostic delay in psoriatic arthritis: insights from a nationwide multicenter study.

This study aimed to investigate the duration of diagnostic delay in patients with psoriatic arthritis (PsA) and identify potential contributing factors using a comprehensive, population-based approach. Data were obtained from the Turkish League Against Rheumatism (TLAR)-Network, involving patients who met the CASPAR criteria. Diagnostic delay was defined as time interval from symptom onset to PsA diagnosis, categorized as ≤ 2 years and > 2 years. Temporal trends were assessed by grouping patients based on the year of diagnosis. Various factors including demographics, clinical characteristics, disease activity, quality of life, physical function, disability, fatigue, and well-being were examined. Logistic regression models were used to identify factors associated with diagnostic delay. Among 1,134 PsA patients, mean diagnostic delay was 35.1 months (median: 12). Approximately 39.15% were diagnosed within 3 months, and 67.02% were diagnosed within 24 months. Patients experiencing longer delays had higher scores in Psoriatic Arthritis Quality of Life Questionnaire (PsAQoL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), patient's global assessment (PtGA) and physician's global assessment (PhGA). Diagnostic delay has decreased over time, with median delay falling from 60 to 24 months throughout pre-2010 and 2015-2019 terms. Several factors were identified as significant contributors to delayed diagnosis, including lower levels ofeducation (OR = 2.63), arthritis symptoms preceding skin manifestations (OR = 1.72), low back pain at first visit (OR = 1.60), symptom onset age (OR = 0.96), and psoriasis subtype (OR = 0.25). Timely diagnosis of PsA is crucial for effective management and improved outcomes. Despite recent improvements, about one-third of PsA patients still experience delays exceeding 2 years. By identifying influential factors such as education level, arthritis symptoms preceding skin manifestations, initial visit symptoms, age of symptom onset, and psoriasis subtype, healthcare practitioners may create specific techniques to help in early detection and intervention.

THU187 Genotype-Phenotype Correlation, Clinical Presentation And Feminizing Surgery In Children With Congenital Adrenal Hyperplasia Due To 21-Hydroxylase Deficiency: A Nationwide Multi-Center Study

Abstract Disclosure: M. Lind-Holst: None. A. Berglund: None. M. Duno: None. G. Hvistendahl: None. M. Fossum: None. A. Juul: None. N. Jørgensen: None. K.M. Main: None. C.H. Gravholt: None. D. Hansen: None. Background: Congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency (21OHD) is a common autosomal recessive disorder caused by pathogenic variants in CYP21A2. Genotype cannot always predict severity and clinical consequences, and genotype-phenotype is only well correlated in the most severe clinical cases of CAH. Furthermore, non-classical CAH suffers from non-diagnosis, especially in males. Objective: Describe the genotype-phenotype correlation in Danish children with 21OHD and identify the most frequent pathogenic CYP21A2 variants. We describe the clinical manifestations at time of diagnosis and present data on virilization and feminizing surgery of females, stratified by genotype group during 20 years. Method: A national population-based study of all Danish children diagnosed with 21OHD, combining health registries and medical record data. We identified pathogenic variants in CYP21A2 and genotype-phenotype correlation. Clinical presentation at diagnosis and feminizing surgery in females was stratified by genotype group: Null, A, B, C and D, reflecting the preserved 21-hydroxylase activity in increasing order. Results: Variants frequency of 494 unique alleles: Deletion (31.8%) followed by I2G, Q318X, I172N, V281L, P30L, Cluster-E6, R356W and insT by 25.9%, 9.1%, 8.6%, 8.7%, 6.5%, 1.4%, 1.4% and 0.6%, respectively. Genotype-phenotype correlations: Null: 98%, A: 94%, B: 50%, C: 76%. Overall, 62 of the 159 children (67%) had evidence of pseudo-precocious puberty at time of diagnosis which was the most frequent group of symptoms in genotype group B: 8.2%, C: 23.3% and D: 3.8%. Bone age advancement was significantly more advanced at the time of diagnosis in males compared to females (p=0.0009). The most frequently reported symptom at diagnosis in the genotype group null (n=20) and A (n=31) were: clitoral hypertrophy in females: 62.7%, failure to thrive: 29% and salt-wasting crisis: 22%. Clitoral hypertrophy was also present in genotype group B, C and D and feminizing surgery was performed in 85% of prenatally virilized females and overall in 40% of females at a median age of 0.9 years [IQR 0.5-1.6]. Conclusion: Genotype groups only predict phenotype with high certainty in the null and A genotype groups. In a national cohort evidence of virilization in females and feminizing surgery were observed in every genotype group. Delayed or non-diagnosis in children with SV and NC CAH was substantial, especially in males. We suggest that children with even mild hyperandrogenic symptoms and normal biochemical markers for 21OHD may benefit from genetic testing for CAH to establish a diagnosis. Presentation: Thursday, June 15, 2023

Drug-Induced Hypersensitivity Syndrome/Drug Reaction With Eosinophilia and Systemic Symptoms: Predictive Score and Outcomes.

We previously developed a drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) severity (DDS) score that may predict DIHS/DRESS-associated complications (DACs), including myocarditis, gastrointestinal bleeding, and autoimmune diseases. To externally confirm the predictive accuracy of the DDS score, clarify its ability to identify patients at high risk of DACs and fatal outcome, and determine which treatments might reduce or increase the risk. We conducted a nationwide multicenter retrospective study in which we followed 48 patients with DIHS/DRESS at 5 university hospitals in Japan for 1 year after onset. Patients were divided into mild, moderate, and severe DIHS/DRESS groups depending on their early DDS score. Eight cases had DACs in the severe group (n= 17); no DACs were observed in the mild group (n= 12). Receiver-operating characteristic curve analysis showed that a cutoff DDS score of ≥4.0 and ≤2.0 could differentiate patients who would and would not develop DACs, respectively. In the moderate-to-severe disease groups, DACs occurred only in patients who received corticosteroids and not in those who received supportive care. None of the patients who received early treatment for cytomegalovirus developed DACs. Autoimmune DACs were significantly more common in patients who received pulse corticosteroid therapy. Four deaths occurred within the 1-year follow-up; all were in patients with infectious DACs who received systemic corticosteroids. Our scoring system allows early identification of patients at increased risk for DACs. Risk factors for DACs include systemic or pulse corticosteroid therapy.

The Japanese Nationwide Cohort Data of Particle Beam Therapy for Liver Oligometastasis in Esophagogastric Cancer Patients

A nationwide multicenter cohort study on particle therapy was launched by the Japanese Society for Radiation Oncology (JASTRO) in Japan in May 2016. We analyzed the outcome of proton beam therapy (PBT) for liver oligometastasis of esophagogastric cancers. Cases in which PBT was performed at all PBT facilities in Japan between May 2016 and February 2019 were enrolled. The patients were selected based on the following criteria: controlled primary cancer; liver recurrence without extrahepatic tumors; and no more than three liver lesions. The dose and fraction of PBT were determined using unified treatment policy established by JASTRO. We used the following protocol, 64 gray (relative biological effect) (Gy (RBE))/8 fractions (fr) for the peripheral region, and 72.6 GyE/22fr for the central region. For safety aspect, the hepatocellular carcinoma irradiation protocols of 66 Gy (RBE)/10fr, 72.6-76 Gy (RBE)/20-22fr, and 74-76 Gy (RBE)/37-38fr could be allowed. The overall survival (OS), local control (LC), and adverse events (AEs) were examined. The OS and LC rates were calculated using the Kaplan-Meier method. Factors possibly related to OS, such as tumor size (for multiple lesions, the largest size), number of liver tumors, as well as the presence or absence of prior, concurrent, and post-PBT chemotherapy, were investigated. The cut-off values were estimated using the receiver operating characteristic curve and area under the curve. Univariate analysis was performed using the log-rank test. Statistical significance was P-values < 0.05. Twenty-three males and two females with a median age of 69 (range, 52-80) years and 36 lesions were included. This study included six patients with esophageal and 19 patients with gastric cancer. The median lesion size, fraction size, and biological effective dose (BED)10 were 31 (7-104) mm, 3.8 gray (relative biological effect)/fractions (Gy (RBE)/fr) (2-8 Gy (RBE)/fr), and 96.9 (88.8-115.2) Gy, respectively. The median follow-up period was 18 (4-47) months. The 1-, 2-, and 3-year OS rates were 76.0, 49.5, and 43.3%, respectively, and the median OS was 19 months. The 1-, 2-, and 3-year OS rates of esophageal cancer were 83.3% for all. The 1-, 2-, and 3-year OS rates of gastric cancer were 73.7, 40.2, and 32.2%, respectively, and the median OS was 18 months. The 1-, 2-, and 3-year LC rates were 96.3, 91.5, and 91.5%, respectively. The 1-, 2-, and 3-year LC rates of esophageal cancer were 100% for all. The 1-, 2-, and 3-year LC rates of gastric cancers were 94.7, 88.0, and 88.0%, respectively. Tumor size was the only significant OS-related factor (P < 0.01). No grade 3 or higher adverse events were observed. Owing to the low incidence of adverse events and the high LC rate, PBT is a feasible option for liver oligometastasis of esophagogastric cancers.

The Japanese Nationwide Cohort Data of Proton Beam Therapy for Liver Oligometastasis in Breast Cancer Patients

A nationwide multicenter cohort study on particle therapy was launched by the Japanese Society for Radiation Oncology (JASTRO) in Japan. We analyzed the outcome of proton beam therapy (PBT) for liver oligometastasis in breast cancers. Cases in which PBT was performed at all Japanese proton therapy facilities between May 2016 and February 2019 were enrolled. The patients were selected based on the following criteria: the primary cancer was controlled, liver recurrence without extrahepatic tumors, and no more than three liver lesions. The treatment indication and strategy were discussed at cancer boards in each institution. The dose and fraction of PBT were determined by referring to the unified treatment policy established by JASTRO. We used the following protocol: 64 gray (Gy) (relative biological effectiveness [RBE])/8 fraction (fr) for the hepatic periphery area away from the GI tract, and 72.6 GyE/22 fr for the adjacent hilar region type. Regarding safety, the HCC irradiation protocols of 66 GyE/10 fr, 72.6-76 GyE/20-22 fr, and 74-76 GyE/37-38 fr could be used. The local control (LC), overall survival (OS), and progression free survival (PFS) rates were calculated using the Kaplan-Meier method. Factors possibly related to OS, such as tumor size, number of liver tumors, intervention of chemotherapy, and/or hormone therapy, were investigated. The cut-off values were estimated using the receiver operating characteristic curve and area under the curve. Univariate analysis was performed using the log-rank test. Fourteen females, with a median age of 57 (range, 44-73) years and twenty-two lesions were included. Nine patients had one lesion, two patients had two lesions, and three patients had three lesions. PBT was selected because nine patients had underlying disease and five patients had general conditions (age, etc.). The median lesion size, fraction size, and biological effective dose using the linear-quadratic model with α/β = 10 Gy ((BED)10) were 44 (20-130) mm, 6.6 (2-8) (relative biological effectiveness [RBE])/fraction (fr), and 109.6 (52.7-115.2) Gy, respectively. The median follow-up period of breast cancers was 22.8 (4-54) months. The 1-, 2-, and 3-year LC rates of liver metastasis from breast cancers were 100% for all. The 1-, 2-, and 3-year OS rates were 85.7%, 62.5%, and 62.5%, respectively. The 1-, 2-, and 3-year PFS rates were 50.0%, 33.3%, and 16.7%, respectively, and median PFS time was 16 months. Tumor size, the number of liver tumors, and the intervention of chemotherapy and/or hormone therapy at any time were not significantly related to the OS. Only one patient did not complete PBT due to current disease progression. The other patients completed PBT without interruption. One patient had grade 3 radiation-induced dermatitis. Based on the low incidence of adverse events and the high LC rate, PBT appears to be a feasible option for liver oligometastasis in breast cancer patients.

NGS analysis of collagen type I genes in Polish patients with Osteogenesis imperfecta: a nationwide multicenter study.

Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue. It presents with a wide spectrum of skeletal and extraskeletal features, and ranges in severity from mild to perinatal lethal. The disease is characterized by a heterogeneous genetic background, where approximately 85%-90% of cases have dominantly inherited heterozygous pathogenic variants located in the COL1A1 and COL1A2 genes. This paper presents the results of the first nationwide study, performed on a large cohort of 197 Polish OI patients. Variants were identified using a next-generation sequencing (NGS) custom gene panel and multiplex ligation probe amplification (MLPA) assay. The following OI types were observed: 1 (42%), 2 (3%), 3 (35%), and 4 (20%). Collagen type I pathogenic variants were reported in 108 families. Alterations were observed in α1 and α2 in 70% and 30% of cases, respectively. The presented paper reports 97 distinct causative variants and expands the OI database with 38 novel pathogenic changes. It also enabled the identification of the first glycine-to-tryptophan substitution in the COL1A1 gene and brought new insights into the clinical severity associated with variants localized in "lethal regions". Our results contribute to a better understanding of the clinical and genetic aspects of OI.