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Abstract Background Health-related quality of life (HRQoL) is impaired in patients with Crohn’s disease (CD). Upadacitinib (UPA), a Janus kinase inhibitor, demonstrated efficacy and safety in the phase 3 U-EXCEED (NCT03345836) and U-EXCEL (NCT03345849) induction, and U-ENDURE (NCT03345823) maintenance trials in patients with moderately to severely active CD. We assessed the effect of UPA maintenance treatment on HRQoL in patients with moderately to severely active CD from the U-ENDURE long-term extension (LTE) study. Methods Patients who completed the 52-week U-ENDURE maintenance study were eligible to participate in the LTE study, continuing their previously assigned maintenance treatment. Of the 337 patients receiving UPA (168, UPA 30 mg; 169, UPA 15 mg) in the U-ENDURE maintenance trial, a total of 244 patients (137, UPA 30 mg; 107, UPA 15 mg) were included in this analysis. All 244 patients completed week 96 of the LTE. Endpoints included percentage of patients who achieved Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase from induction baseline), IBDQ remission (total score ≥170 points), a meaningful within-person change (MWPC) of ≥ 9point increase from baseline in the Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-F) and a MWPC of ≥ 4.1- and ≥3.9-point increase from baseline on the 36-item Short Form Health Survey (SF-36) physical (PCS) and mental (MCS) component summary score, respectively, at maintenance week 52 and LTE week 96. We also assessed MWPC in Work Productivity and Activity Impairment in CD (WPAI-CD) domains defined as a decrease of ≥ 6.1% in presenteeism, ≥6.5% in absenteeism, ≥7.3% in overall work impairment and ≥8.5% in activity impairment. Data were reported using nonresponder imputation. Results The proportion of patients in the UPA 30 mg group achieving HRQoL outcomes was maintained from maintenance week 52 to LTE week 96, including achievement of IBDQ response (61.3% vs 57.7%), IBDQ remission (53.3% vs 53.3%), MWPC improvement in FACIT-F (50.4% vs 40.9%), SF-36 PCS (56.9% vs 56.2%), SF-36 MCS (47.4% vs 40.9%) and MWPC improvements in WPAI-CD domains presenteeism (45.6% vs 48.1%), overall work impairment (49.4% vs 51.9%) and daily activity impairment (57.7% vs 56.9%). Patients in the UPA 15 mg group also maintained achievement of these HRQoL outcomes over time (Table). Conclusion UPA (15 and 30 mg) maintenance treatment over a 3-year period was associated with sustained and clinically meaningful disease-specific and generic HRQoL improvement in patients with moderately to severely active CD. Despite the overall trend favouring UPA 30 mg, differences in patient-reported outcomes between the 2 dose groups were small. Conflict of interest: Panés, Julián: Personal Fees: J. Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Boehringer Ingelheim, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Spyre Therapeutics, Surrozen, Takeda, and Wasserman, and has served on data safety monitoring boards for Alimentiv, Mirum, Roche, Sorriso, Sanofi, and Surrozen Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Bossuyt, Peter: Grant support for research from AbbVie, EG Consulting fee from AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Jeito capital, Lilly, Pentax, Pfizer, PSI-CRO, Roche, Takeda, Tetrameros Speakers fee from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media Joshi, Namita: Namita Joshi is a full-time employees/contractor of AbbVie and may own AbbVie stock or options. Xuan, Si: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Shukla, Nidhi: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Dubcenco, Elena: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Aponte, Fernando: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Perkovic, Ashley: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Loftus, Jr, Edward: Grant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, UCB. Personal Fees: AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Iterative Scopes, Janssen, Ono Pharma, Pfizer, Sun Pharma, Takeda, UCB.

Abstract Background Endoscopic healing is an important treatment goal in Crohn’s disease (CD), in line with European Crohn’s and Colitis Organisation CD guidelines, as it is associated with improved long-term disease outcomes. We assessed the relationship between endoscopic healing and long-term clinical outcomes, patient-reported outcomes (PROs) and hospitalisations in patients (pts) with moderately to severely active CD receiving upadacitinib (UPA) maintenance treatment in the U-ENDURE long-term extension (LTE) study. Methods Pts completing the 52-week U-ENDURE maintenance study were eligible to participate in the LTE study, continuing their previously assigned maintenance treatment. Pts receiving UPA 15 mg or 30 mg once daily in LTE were included in this analysis. Clinical remission based on CD activity index (CDAI <150), CDAI response (≥100-point decrease in CDAI from induction baseline), clinical remission based on stool frequency/abdominal pain (SF/AP) score (average daily soft or liquid SF ≤ 2.8 and average daily AP ≤ 1.0, and neither greater than induction baseline), Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase in total IBDQ score from induction baseline) and remission (IBDQ total score ≥170 points), Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-F) response (≥9-point increase from induction baseline), and economic outcomes (CD-related hospitalisations or surgeries) were evaluated at LTE week 96. Outcomes were compared between pts who achieved vs those who did not achieve endoscopic response, endoscopic remission, or ulcer-free endoscopy (endoscopic outcomes defined in Table footnote) at maintenance week 52 using chi-square testing (nominal P values). Pts with missing outcomes at LTE week 96 were imputed as nonresponders. Results Of 244 pts, 153/244 (62.7%), 112/244 (45.9%) and 89/242 (36.8%) achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at LTE week 0. Significantly (all nominal P≤0.05) more pts who achieved endoscopic response, endoscopic remission or had an ulcer-free endoscopy at LTE Week 0 achieved CDAI response, CDAI remission, SF/AP clinical remission, IBDQ response, IBDQ remission and FACIT-F response at LTE week 96 (Table). CD-related hospitalisations or surgeries at LTE week 96, were significantly (nominal P≤0.05) lower in pts with endoscopic remission and ulcer-free endoscopy at LTE week 0, and numerically lower in pts with endoscopic response. Conclusion A significantly higher proportion of pts who achieved endoscopic outcomes at 52 weeks and received up to 3 years of UPA maintenance treatment achieved long-term improvements in clinical and PROs and reduced CD-related hospitalisations or surgeries. Conflict of interest: Loftus, Jr, Edward: Edward V. Loftus, Jr. has received consulting fees from AbbVie, Abivax, Astellas, Avalo Therapeutics, Biocon, BMS, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Merck, Morphic Therapeutics, Ono Pharma, Spyre Therapeutics, Takeda, and TR1X Bio has received research support from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda and holds stock in Exact Sciences and Moderna. Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Bossuyt, Peter: Grant support for research from AbbVie, EG Consulting fee from AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Jeito capital, Lilly, Pentax, Pfizer, PSI-CRO, Roche, Takeda, Tetrameros Speakers fee from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media Joshi, Namita: Namita Joshi is a full-time employees/contractor of AbbVie and may own AbbVie stock or options. Shukla, Nidhi: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Dubcenco, Elena: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Aponte, Fernando: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Perkovic, Ashley: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Panés, Julián: Personal Fees: J. Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Boehringer Ingelheim, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Spyre Therapeutics, Surrozen, Takeda, and Wasserman, and has served on data safety monitoring boards for Alimentiv, Mirum, Roche, Sorriso, Sanofi, and Surrozen

Abstract Diameter of the aorta is a significant contributor and predictor for complications and a fundamental parameter for intervention. It is recognized that age, sex, and ethnicity play a role in aortic size. We thus sought to determine the normal dimensions among our population. A retrospective analysis of images was done of all polytrauma patients admitted between January 2018 and December 2022 who underwent protocolized noncontrast computed tomography of the chest and abdomen to measure the aortic diameter at established reference points. There were 513 patients; the mean age was 36.5 ± 14.6 (range: 18–86), and 382 (74.5%) were males. Aortic dimensions at sinus, mid-ascending, arch, descending, suprarenal, and infrarenal aorta were 30.7 ± 3.8, 29.3 ± 4.5, 24.9 ± 3.3, 20.1 ± 3.0, 19.4 ± 2.9, and 15.3 ± 2.2, respectively. Age demonstrated a positive correlation to the diameter at the ascending, descending, and infrarenal aorta (r = 0.58, p = 0.001 [95% confidence interval, CI = 0.519; 0.634]; r = 0.69, p = 0.001 [95% CI = 0.641; 0.732]; r = 0.57, p = 0.001 [95% CI = 0.509; 0.626]) along with the length of the ascending aorta (r = 0.420, p = 0.001 [95% CI = 0.345; 0.488]; r = 0.536, p = 0.001 [95% CI = 0.471; 0.595]; r = 0.476, p = 0.001 [95% CI = 0.406; 0.540), respectively. There was a positive correlation of aortic diameters to body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Females had smaller dimension at the reference points, but without any statistical significance. There were 50 (9.8%) patients with bovine aortic arch and 10 (1.9%) with separate origin of left vertebral artery. Normal values of the diameter of the aorta for a South Asian population are provided. Diameter is affected by age, length of the ascending aorta, BMI, SBP, and DBP. This study suggests that the aorta size is smaller in the South Asian population than the referenced Western population, more significantly for distal descending and abdominal aorta and that ethnicity plays a role in determining aortic dimensions.

Abstract Background Good syndrome (GS) is an under-recognized adult-onset immunodeficiency characterized by the coexistence of thymoma and hypogammaglobulinemia. It is marked by recurrent infections, combined B- and T-cell immunodeficiency, and frequent autoimmune manifestations. Its rarity, unclear pathogenesis, and often delayed diagnosis contribute to its clinical complexity.Distribution of Infections by pathogen type in patients with Good Syndrome: the microbiological spectrumDemographics, clinical characteristics, thymoma classification with staging and management Methods We conducted a retrospective review of adults diagnosed with good syndrome at Mayo Clinic up until 2024. We assessed baseline characteristics, clinical features with a particular focus on infectious complications, immunological lab parameters, thymoma histopathology with staging, and management. Descriptive statistics were utilized for analysis.Immunological lab parameters and management of Good syndrome Results During the study period, Good syndrome was diagnosed in 32 patients; 78% were male, with a median age at diagnosis of 62 years (Table 1). All patients had thymoma, the majority of which were stage I (localized), and most underwent thymectomy as part of management. The median delay in GS diagnosis following thymoma diagnosis was 1,486 days (interquartile range IQR: 406.75–1,992.75). Infectious complications were observed in 30 of 32 patients (97%), most commonly sinopulmonary infections (87%) (Figure 1). Bacterial infections were documented in 29 patients (94%), viral in 14 (45%), fungal in 13 (42%), and mycobacterial in 3 (10%) (Figure 2). Immunologic data were available for 22 patients. Reduced CD4+ T-cell counts and severe B-cell lymphopenia were observed in 77%. IgM and IgG deficiencies were the most prevalent, present in 82% of cases. Most patients received monthly immunoglobulin replacement; additionally, 59% were prescribed oral antimicrobial prophylaxis due to their elevated risk of infections. All-cause mortality was 31% (n=10); among these, 3 deaths (10%) were directly attributable to complications of Good syndrome. Conclusion We observed a significant delay (Median of 4.07 years) in the diagnosis of Good syndrome following thymoma detection. Given the high risk of infectious complications and associated mortality, clinicians should maintain a high index of suspicion and consider early immunologic evaluation in adults with recurrent or opportunistic infections, particularly in the context of a known thymoma. Disclosures All Authors: No reported disclosures

This practice guideline addresses perioperative pain management using local and regional anesthesia for cardiothoracic, mastectomy, and abdominal surgery in adults and children. For adults, the American Society of Anesthesiologists (Schaumburg, Illinois) Task Force on Perioperative Pain Management strongly recommends fascial plane blocks to reduce pain and/or opioid requirements in the first 24 h postoperatively for open cardiothoracic, abdominal, retroperitoneal, and pelvic surgeries and mastectomy. Fascial plane blocks are also recommended in adults to reduce pain and/or opioid requirements after minimally invasive abdominal procedures. The Task Force conditionally recommends use of fascial plane blocks for minimally invasive cardiothoracic surgeries and open hernia repair to reduce pain in the first 24 h postoperatively. For children, the Task Force strongly recommends use of fascial plane blocks to reduce pain/and or opioid use after open cardiac or thoracic surgeries. Fascial plane blocks are conditionally recommended to reduce pain the first 24 h in children undergoing open hernia repair. Overall, data analysis for this practice guideline was limited by low methodologic quality, inconsistencies in outcome measurements, and small sample sizes from individual centers. Future research in regional anesthesia and analgesia needs to address these pervasive limitations.

Abstract Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced-intensity regimens were associated with lower T-cell and myeloid donor chimerism, particularly when non–busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hot spot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS, or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS after HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This trial was registered at www.clinicaltrials.gov as NCT02064933.

Abstract Background: Chronic myelomonocytic leukemia (CMML) is a universally fatal adult myeloid neoplasm with a median survival of 32 months and no approved therapies that alter its natural history. Although most patients initially present asymptomatically, disease progression (DP) is inevitable and its biological triggers remain poorly understood. Anecdotes and small case series suggest that acute inflammatory events (AIE) may precipitate hyperleukocytosis and DP in some patients, but fragmented care in the U.S. has hindered large-scale retrospective analyses. To address this gap, we launched a prospective, multi-institutional observational study to systematically evaluate the relationship between AIEs and DP. Our aim is to identify modifiable, cell-extrinsic stressors that contribute to disease destabilization and inform strategies for prolonging the indolent phase of CMML. Methods: We enrolled patients with WHO-defined CMML in a clinically asymptomatic state, defined by: (1) MPN-SAF TSS <20, (2) no CMML-directed therapy, (3) no symptomatic splenomegaly, and (4) transfusion independence. Key exclusions included active malignancy, uncontrolled infection, or inability to attend monthly visits. Over 24 months, participants underwent monthly interviews to document AIEs, including flares of chronic illness e.g. gout, infections, surgery procedures, cardiovascular events, and trauma. AIE severity was graded by hospitalization status. Blood samples were collected at each visit, with bone marrow collected when clinically indicated. Cytokine profiling was performed using Olink Reveal assays, and genomic data were integrated to assess mutation-specific inflammatory patterns. DP was defined by worsening symptoms (MPN-SAF TSS ≥20 with ≥50% increase), new transfusion needs, therapy initiation, symptomatic splenomegaly, or transformation to CMML-2/AML. Descriptive statistics summarized baseline and AIE data. Progression-free (PFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression models. Results: A total of 102 patients were enrolled over 2 years, with a median follow-up of 1 year (range, 0.5–1.5). The median age was 72 years; 71 were male and 31 female. By FAB criteria, 38 had myeloproliferative-type CMML, and 8 met WHO 2022 criteria for CMML-2. CPSS-Mol risk distribution was: 49.0% low, 26.5% intermediate-1, 37.3% intermediate-2, and 3.99% high. A total of 260 AIE were recorded in 77 patients. The most common AIEs were surgical procedures (n=115 events in 53 patients), flares of chronic disease (n=99 in 38), and infections (n=87 in 47). DP occurred in 28 patients: 18 met symptom-defined criteria, 13 met disease-defined criteria, and 3 met both. Longitudinal labs showed significant post-AIE increases in WBC (6.29 → 7.73 ×10⁹/L, p = 0.02) and platelets (112 → 131 ×10⁹/L, p = 0.03), with no change in hemoglobin (p = 0.27). Progressors had significantly lower hemoglobin than non-progressors (11.6 vs. 12.7 g/dL, p = 0.037), with no differences in WBC or platelet counts (p > 0.5). Among those with DP, 25 of 28 had at least one AIE. AIE presence was significantly associated with DP (OR 3.76, p = 0.04). Flares of chronic disease conferred a threefold increased risk of DP (OR 3.37, p = 0.008) and remained an independent risk factor after adjusting for CPSS-Mol risk (OR 3.6, p = 0.009). Severe AIEs requiring hospitalization trended toward higher risk but were not statistically significant (OR 2.3, p = 0.09). Among the 44 patients with genomic data, all AIE-positive patients (29/29) harbored at least one epigenetic regulator mutations (TET2, DNMT3A, ASXL1, IDH1/2), compared to 12/15 AIE-negative patients (p = 0.034). Signaling mutations (JAK2, CBL, NRAS, KRAS) were also enriched in AIE-positive cases (11/29 vs. 1/15, p = 0.035). No significant differences were found in spliceosome or tumor suppressor mutations. No genomic features distinguished progressors from non-progressors, regardless of whether there was an AIE. Conclusion: In this interim analysis of a prospective multi-institutional CMML cohort, AIE were significantly associated with DP. Ongoing work is aimed at sequentially annotating genomic alterations and profiling secreted factors before and after AIEs. While this study continues to accrue and mature, these findings support inflammation as a modifiable driver to CMML biology and progression and lay the groundwork for future studies investigating inflammatory or supportive interventions to delay disease evolution.

Abstract Background Thrombotic Thrombocytopenic Purpura (TTP) is a rare, typically acquired disorder due to an immune-mediated deficiency of ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand Factor (vWF). In the absence of ADAMTS13 activity, ultra-large vWF multimers accumulate, promoting widespread platelet aggregation and microvascular thrombosis. This consumptive cascade leads to thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and rarely renal dysfunction. Although therapeutic plasma exchange (TPE) has long been the cornerstone of TTP treatment, the FDA approved Caplacizumab as a first-line treatment for TTP in 2019. This drug is a bivalent single-domain antibody that binds to the A1 domain of vWF and prevents its interaction with platelets, thus effectively interrupting the pathogenic cascade, which is associated with a risk of bleeding. Methods We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, comprising data from 152 healthcare organizations. Adults (≥18 years) with a diagnosis of TTP who received Caplacizumab plus TPE were compared to patients with TTP who received TPE alone. 1:1 propensity score matching (PSM) was performed to balance characteristics between cohorts. The primary outcomes assessed were all-cause mortality and major bleeding events over a period of 1 month. Results A total of 4084 patients with TTP were identified, of whom 356 received caplacizumab with TPE and 3728 received TPE. After PSM, 2 balanced cohorts were created: C+P (Caplacizumab + TPE), P only (TPE), each comprising 356 patients. The average age in C+P and P only, after PSM, was 50.4 +/- 16.2 and 50.8 +/- 16.2 years, respectively. Females formed 65.7% of both C+P and P only, and males accounted for 28.4% and 28.7% of C+P and P only, respectively. 2.8% patients in C+P and 7.06% patients in P only had all-cause mortality at the end of 1 month. One-month all-cause mortality was significantly lower in C+P (2.8%) compared to P only (7.06%), with an odds ratio (OR) of 0.385 (95% CI 0.182 to 0.814, p=0.010). Upon assessment of bleeding outcomes, no statistically significant risk difference was noted between the 2 groups, with the odds ratio being 0.974 (95% CI 0.399 to 2.379, p=0.954). Conclusion Our large database study suggests that the addition of caplacizumab to standard TPE therapy is associated with a reduction in one-month all-cause mortality in patients with TTP, without a corresponding increase in major bleeding. However, given the lack of granular clinical data, such as contraindications to caplacizumab use, it is possible that patients who received TPE alone were inherently at a higher risk. As such, while these findings support the potential benefit of early caplacizumab use, they should be interpreted with caution and warrant prospective validation to confirm causality and assess long-term outcomes.

Abstract Background: Patients with myelodysplastic syndromes (MDS) are at heightened risk for severe infections, including sepsis, due to underlying cytopenias and immune dysregulation. Hospital-level characteristics, including size and available resources, may influence clinical outcomes in these patients, but data remain limited. This study examines the association between hospital bed size and sepsis-related complications in patients with MDS using a nationally representative dataset. Methods: We conducted a retrospective cohort analysis using the National Inpatient Sample (NIS) from 2016 to 2022, identifying adult hospitalizations with co-diagnoses of MDS and sepsis. Hospitalizations were stratified by hospital bed size: small (n = 15,490), medium (n = 22,815), and large (n = 40,245). Multivariable logistic regression, adjusted for patient demographics, comorbidities, and hospital characteristics, was used to assess associations between hospital bed size and eight clinical outcomes: in-hospital mortality, septic shock, acute renal failure, respiratory failure, encephalopathy, disseminated intravascular coagulation (DIC), Clostridioides difficile infection (CDI), and fungal sepsis. Results: Compared to small hospitals, patients treated at large hospitals had significantly higher odds of in-hospital mortality (OR 1.43, p < 0.001), septic shock (OR 1.25, p < 0.001), acute renal failure (OR 1.10, p < 0.001), encephalopathy (OR 1.11, p = 0.004), DIC (OR 1.48, p = 0.007), and fungal sepsis (OR 2.13, p = 0.028). Medium-sized hospitals were also associated with increased odds of mortality (OR 1.16, p = 0.021) and septic shock (OR 1.13, p = 0.038). No statistically significant differences were found in rates of CDI across hospital sizes. Respiratory failure showed a borderline association in medium hospitals (OR 1.05, p = 0.082) but not in large hospitals. Conclusion: Hospital bed size is independently associated with important variations in sepsis-related outcomes among patients with MDS. Large hospitals demonstrated significantly increased odds of multiple complications and mortality, possibly reflecting referral bias, higher disease acuity, or institutional coding practices. These findings underscore the importance of hospital-level factors in evaluating outcomes and resource planning for high-risk hematologic populations. Keywords: Myelodysplastic syndromes, hospital bed size, sepsis, mortality, ICU complications, NIS

Abstract Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders often complicated by infections due to cytopenias. Sepsis is a frequent cause of hospitalization and mortality in MDS patients. Neutropenia, a common feature in MDS, may predispose patients to specific infectious complications, but its impact on sepsis-related outcomes remains poorly characterized. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database from 2016 to 2022. Adult hospitalizations with co-diagnoses of MDS and sepsis were identified using ICD-10-CM codes. Patients were stratified based on the presence or absence of neutropenia. Multivariable logistic regression models were used to evaluate the association between neutropenia and specific in-hospital outcomes, including Clostridioides difficile infection, fungal sepsis, and disseminated intravascular coagulation (DIC). Models were adjusted for age, sex, comorbidities, hospital characteristics, and illness severity. Results: A total of 78,549 hospitalizations involving MDS patients with sepsis were identified, including 11,295 (14.4%) with neutropenia. Neutropenic patients had significantly higher odds of C. difficile infection (adjusted odds ratio [aOR] 1.61, 95% CI 1.30–1.99, p < 0.001) and fungal sepsis (aOR 2.08, 95% CI 1.22–3.54, p = 0.007) compared to those without neutropenia. However, neutropenia was not significantly associated with DIC (aOR 0.84, 95% CI 0.59–1.19, p = 0.322). Conclusion: In this large national cohort, neutropenia was associated with a significantly increased risk of C. difficile infection and fungal sepsis among MDS patients hospitalized with sepsis. These findings highlight the need for early recognition and targeted antimicrobial strategies in neutropenic MDS patients. No significant association was observed between neutropenia and DIC. Future studies should explore preventive strategies and risk stratification tools tailored to this high-risk population. Keywords: Myelodysplastic syndromes, neutropenia, sepsis, NIS, Clostridioides difficile, fungal sepsis, outcomes