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AimsThe scapula is a rare site for a primary bone tumour. Only a small number of series have studied patient outcomes after treatment. Previous studies have shown a high rate of recurrence, with functional outcomes determined by the preservation of the glenohumeral joint and deltoid. The purpose of the current study was to report the outcome of patients who had undergone tumour resection that included the scapula.MethodsWe reviewed 61 patients (37 male, 24 female; mean age 42 years (SD 19)) who had undergone resection of the scapula. The most common resection was type 2 (n = 34) according to the Tikhoff-Linberg classification, or type S1A (n = 35) on the Enneking classification.ResultsThe ten-year disease-specific survival was 76%. High tumour grade (hazard ratio (HR) 4.27; p = 0.016) and a total resection of the scapula (HR 3.84; p = 0.015) were associated with worse survival. The ten-year metastasis-free and local recurrence-free survivals were 82% and 86%, respectively. Total scapular resection (HR 6.29; p = 0.004) was associated with metastatic disease and positive margins were associated with local recurrence (HR 12.86; p = 0.001). At final follow-up, the mean shoulder forward elevation and external rotation were 79° (SD 62°) and 27° (SD 25°), respectively. The most recent functional outcomes evaluated included the mean Musculoskeletal Tumor Society Score (76% (SD 17%)), the American Shoulder and Elbow Score (73% (SD 20%)), and the Simple Shoulder Test (7 (SD 3)). Preservation of the glenoid (p = 0.001) and scapular spine (p < 0.001) improved clinical outcomes; interestingly, preservation of the scapular spine without the glenoid improved outcomes (p < 0.001) compared to preservation of the glenoid alone (p = 0.05).ConclusionResection of the scapula is a major undertaking with an oncological outcome related to tumour grade, and a functional outcome associated with the status of the scapular spine and glenoid. Positive resection margins are associated with local recurrence.Cite this article: Bone Joint J 2023;105-B(12):1314–1320.

AbstractBackgroundPediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT).ProcedureUsing an IRB‐approved prospective outcomes registry, we evaluated patient, tumor, and treatment‐related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT.ResultsFifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow‐up was 4.8 years. No patients were lost to follow‐up. Five‐year disease‐free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in‐field basal cell skin cancer.ConclusionsA multimodality approach for pediatric EN results in excellent local control. Despite the moderate‐dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow‐up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage.

Abstract Background The BioFire® FilmArray® Gastrointestinal Pathogen Panel (GIPP) tests for 22 potential pathogens in stool, including Clostridioides difficile. C. difficile nucleic acid is detected via nested polymerase chain reaction (PCR) targeting toxin A (TcdA) and/or toxin B (TcdB) genes. While PCR-based diagnostic methods are highly sensitive, they lack specificity to differentiate colonization from C. difficile infection (CDI). Mayo Clinic Arizona (MCA) uses enzyme immunoassay (EIA) testing for toxin A/B and glutamate dehydrogenase antigens with reflex to PCR for discordance as the primary algorithm for diagnosing CDI; however, GIPP PCR testing circumvents this algorithm. When used in patients with low pretest probability for CDI, clinical false positives can lead to inappropriate diagnosis and treatment of colonization. GIPA Results in the Electronic Medical Record Pre-Intervention MCA Standalone C. difficile Testing Algorithm Abbreviations – EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic acid amplification test Methods We convened a multidisciplinary quality improvement team to reduce the detection and treatment of C. difficile colonization secondary to GIPP test results. Surveys were sent to providers and nurses as part of a formal gap analysis and included questions around ordering patterns, knowledge of appropriate tests, and associated costs. Baseline data was compiled from GIPP orders in MCA from 1/1/2022-9/30/2022. Results There were 1978 GIPP orders for 1694 patients during the study period (∼7 GIPPs/day). Most orders (65%) originated from ambulatory settings. The most common positive target was C. difficile (355/723, 49%), which resulted in treatment for suspected CDI in 94.9% (337/355) of cases. Of the 49 providers who responded to the survey, 86% ordered the GIPP at least monthly. Testing for C. difficile was the 2nd most common reason for ordering the GIPP. Most providers underestimated the cost of the panel and were unfamiliar with the differences between the GIPP and EIA testing algorithm. Nurses sought clarification on stool samples suitable for GIPP testing. Following education and modifications to ordering in the electronic health record, the decision was made to remove the C. difficile target from the GIPP. Provider Understanding of C. difficile Testing Methods GIPA Results in the Electronic Medical Record Post-Intervention Conclusion Multiplex PCR panels are comprehensive but require careful implementation to facilitate diagnostic stewardship. Facilities with robust standalone C. difficile testing algorithms may consider removing the C. difficile target from the GIPP. Disclosures All Authors: No reported disclosures

Abstract Background Inappropriate use of carbapenems is a major driver of antimicrobial resistance. The intensive care unit (ICU) at Mayo Clinic Arizona had a higher meropenem (MER) days of therapy (DOT) per 1000 patient days (PD) compared to other Mayo Clinic Enterprise sites, despite low rates of Pseudomonal resistance to narrower spectrum anti-pseudomonal beta-lactams. Methods A multidisciplinary team of infectious diseases (ID) and critical care medicine (CCM) physicians and pharmacists was created to reduce inappropriate use of MER in the ICU. The baseline rate of appropriateness was determined by evaluating all MER days in the ICU during Q4 2019 and Q4 2020. Each MER day was designated as appropriate or inappropriate based on pre-determined criteria after review by at least one ID and one CCM member. Discordant days were evaluated by the whole team to achieve consensus. The team provided education to the CCM department on the initiative, baseline data, and strategies to reduce inappropriate MER use. The active intervention included prospective audit and feedback of all patients on MER performed by the ID clinical pharmacists Mon-Fri 0700-1530 in Q4 2022. DOT/1000 PD was assessed for the pre-intervention and intervention periods. Results The baseline rate of inappropriate MER use in the ICU was 52% (442/846 days). The two most common reasons for inappropriate MER use in the baseline period were: susceptible organism for which a narrower agent could have been used (93/442, 21%), and infectious workup/cultures negative (89/442, 20%). During the intervention period, the inappropriate rate of MER use was reduced to 23%, below the pre-determined goal of 30%. The MER DOT/1000 PD in the baseline period were 103.9 (Q4 2019) and 151.5 (Q4 2020) versus 66.1 (Q4 2022) in the intervention period. There was no difference in ICU sepsis-related mortality in the pre-intervention vs intervention period (13.4 vs 0%, p=0.04). Conclusion A multidisciplinary team approach, including education and prospective audit and feedback, reduced inappropriate MER use in the ICU of an academic medical center from 52 to 23%. An associated decrease in MER DOT/1000 patient days was also observed. Disclosures All Authors: No reported disclosures

Abstract Background Bacterial blood stream infection (BSI) is a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient population. This systematic review aims at pooling global data from the leading transplant institutions to identify the overall prevalence and risk factors associated with bacterial BSI and the most common causative organisms. Methods A systematic review of PubMed and OVID databases was conducted for the past 20 years. Initial search from both databases had a yield of 252 unique articles which were reviewed independently by two authors. Data related to demographics, prevalence, organisms and risk factors were extracted from the articles and subsequently analysed. The systematic review was registered on PROSPERO (ID: CRD42023403206). The PRISMA flow diagram visually summarises the screening process Results A total of 14 articles were included from the United States of America, France, Italy, Thailand, Japan, Spain and Korea. A total of 4215 liver transplants were included in the final analysis. The overall prevalence of BSI in pediatric liver transplant patients was 23.5% with the highest prevalence reported in Japan (39.5%) and lowest in the USA (18.7%). Mean age of the patients was 25 months and 54% were females. The most common organisms reported were Staphylococcus epidermidis at 22.8% followed by Enterococcus species (16.6%), Klebsiella species (11.9%) and Escherichia coli (11.4%). Among the risk factors studied, postoperative biliary complications, past medical history of biliary atresia and younger age were the risk factors most associated with BSI. Prevalence of bloodstream infections (BSI) post pediatric liver transplant in included countries. Bacterial organisms isolated in blood cultures in pediatric post liver transplant patient with a bloodstream infection. Conclusion Bacterial BSI post pediatric liver transplantation occurs with high prevalence. Further studies need to be conducted to better define risk factors for BSI and determine the best empirical antibiotic management for BSI in this population as the distribution of organisms varies greatly from otherwise healthy pediatric patients. Disclosures All Authors: No reported disclosures

The human gastrointestinal (GI) tract is home to trillions of microorganisms. There is dynamic interaction between the gut microbiota and the human host, but how gut microbiota modulates GI physiology is largely unknown. A recent study from our laboratory showed that human gut microbiota increases host serotonin (5‐hydroxytryptamine, 5‐HT) biosynthesis. 5‐HT is an important neurotransmitter and a paracrine messenger in the GI tract that increases intestinal secretion primarily through 5‐HT 3 and 5‐HT 4 receptors. In this study we investigated whether gut microbiota modulate 5‐HT 3 R and 5‐HT 4 R expression and host secretory response to 5‐HT. Methods We used proximal colon mucosa‐submucosa preparations from germ free (GF) and humanized (ex‐GF colonized with human bacteria for 4–5 weeks; HM) male mice. The change in short circuit current (ΔIsc) was determined in response to increasing concentrations of 5‐HT (0.003–300μM) on the submucosal side either alone or in the presence of 5‐HT 3 R antagonist ondansetron (100nM) in an Ussing chamber. Receptor expression was quantified using rt‐PCR (normalized to L32) and western blot (normalized to GAPDH). Immunohistochemistry (IHC) was used to determine localization of 5‐HT 3 R in the paraformaldehyde‐fixed 10μm sections from proximal colonic epithelium. Differences between groups were tested using Mann‐Whitney U (Mdn; IQ range) with P ‐value lower than 0.05 considered significant. Results 5‐HT induced ΔIsc was significantly higher in GF than HM mice (218; 184–274 vs 163; 132–182 μA/cm 2 , n=6, P = 0.04). To determine if this change was due to an alteration in 5‐HTR, we quantified receptor expression. We found significantly higher 5‐HT 3 R mRNA expression (1.82; 1.08–2.80 vs 1.00; 0.33–1.38, n=8–9, P = 0.046) in GF compared to HM mice, but no change in 5‐HT 4 R expression. 5‐HT 3 R protein expression was also significantly higher in GF mice compared to HM (4.62; 1.06–6.14 vs 1.00; 1–1.3, n= 11–12, P = 0.01) mice. There was a significantly higher ΔIsc in GF compared to HM (87.1; 51.7–149 vs 37.0; 19.5–44 μA/cm 2 , n=5, P = 0.02) mice, following application of 2‐methyl 5‐hydroxytryptamine hydrochloride (selective 5‐HT 3 R agonist) suggesting increased receptor expression augments secretory response. Furthermore, ondansetron significantly blocked 5‐HT induced maximum ΔIsc in GF mice (201; 189–260 vs 117.6; 92–149 μA/cm 2 , n=6–8, P = 0.001) but not in HM mice (163; 132–182 vs 120; 107–150 μA/cm 2 , n=6, P = 0.24). To determine the expression of 5‐HT 3 R in mouse colon mucosa‐submucosa we used 5‐HT 3 –tagged GFP mice. IHC identified 5‐HT 3 R‐GFP positive cells in the mouse colonic epithelium. To ascertain if the significant difference in 5‐HT‐induced ΔIsc between GF and HM mice (188; 152–200 vs 125; 99–139 μA/cm 2 , n=5, P = 0.008) is driven by epithelial 5‐HT 3 R, we measured the response in the presence of TTX (block neuronal transmission). TTX (500 nM) had no effect of ondansetron inhibition of 5‐HT‐induced ΔIsc, suggesting a role for epithelial 5HT 3 R. Conclusion Gut microbial colonization decreases host secretory response to 5‐HT by downregulating 5‐HT 3 R expression. Epithelial 5‐HT 3 R may be important in gut microbiota modulation of intestinal secretion Support or Funding Information NIH K08 DK

Background Therapy for celiac disease (CD) mainly relies on following a gluten‐free diet (GFD); however, a serum marker for gluten intake has yet to be established. Aims To evaluate the utility of alkylresorcinol concentrations for detecting gluten intake in studies of human and mouse. Methods Alkylresorcinol concentrations were compared among treated CD patients (n=34), untreated CD patients (n=36), and controls (n=33). Furthermore, 7 additional CD patients whose serum samples were available at diagnosis and after GFD were evaluated. In mice studies, alkylresorcinol concentrations were compared in the serum of 5 mice fed a regular chow and 10 mice fed lifelong with a gluten‐free chow. In addition, the effect of adding gluten on changes of alkylresorcinol concentrations was also evaluated. Results Total alkylresorcinol concentrations were significantly lower in treated CD patients (median [IQR], 3 (2–8) nmol/L), compared to untreated CD patients (median [IQR], 32 [11–74] nmol/L; P<.0001) or healthy controls (median [IQR], 54 [23–112] nmol/L; P<.0001). Moreover, alkylresorcinol concentrations in CD patients significantly decreased after introduction of a GFD (median, 34 nmol/L at diagnosis vs. 5 nmol.L after GFD, p=0.02). In the mice, median (IQR) total alkylresorcinol concentrations in serum samples of mice fed lifelong with a gluten‐free chow was 1.8 (1.6–2.3) nmol/L, which was further significantly increased to 16 (11–22) nmol/L after 8 days of feeding with the gluten free chow that had gluten added to it. (p=.008). Conclusion Serum alkylresorcinol concentrations could be a useful marker for dietary gluten in CD. Support or Funding Information No funding to report.

INTRODUCTION Treatment with β‐antagonists in heart failure (HF) elicits known cardioprotective benefits. Recent work has suggested that administration of a β‐agonist can induce lung fluid clearance in healthy subjects and HF patients. However, the impact of β‐antagonists on the diffusing capacity of the lungs for carbon monoxide (DLCO, to assess lung fluid changes) remains unclear. PURPOSE To examine the relationship between β‐antagonist use and lung diffusion in HF patients. METHODS A retrospective analysis was performed on 102 HF patients seen at Mayo Clinic between 1995–2010. Patients were divided into two groups: BB=patients prescribed β‐antagonists (n=70) and NB=patients not prescribed β‐antagonists (n=32). Medical records were examined ±1 year from the time of the most recent exercise stress test for age (yrs), sex, height (cm), weight (kg), body mass index (BMI) and β‐antagonist status. Outcome variables included DLCO, left ventricular ejection fraction (LVEF), cardiac output (Q), and cardiac output corrected for body surface area (CI). Independent‐samples t‐test compared age, height, weight, and BMI between BB and NB. A Chi‐Squared test compared New York Heart Association (NYHA) classification and sex between NB and BB. Comparison of DLCO, LVEF, Q, CI, DLCO corrected for CI (DLCO/CI), and DLCO corrected for Q (DLCO/Q) between NB and BB was performed with an independent‐samples t‐test. Data are reported as mean ± standard deviation (SD) or frequency (percentage) where applicable. RESULTS There were no differences in age (75±12 vs. 76±13yrs), height (172±10 vs. 173±9cm), weight (84±20 vs. 86±18kg), or BMI (28±6 vs. 29±5kg/m 2 ) between NB vs. BB, respectively. Neither NYHA classification (χ 2 =0.159; p =0.98) or sex (χ 2 =0.066; p =0.80) were different between NB and BB groups. No differences were found for LVEF (36.8±17.3 vs. 31.6±15.6%) or DLCO (20.32±7.6 vs. 19.35±5.7ml/min/mmHg) for NB vs. BB, respectively. Compared to NB, the BB group demonstrated lower CI (0.72±0.3 vs. 0.56±0.3, p =0.006) and Q (1.47±0.6 vs. 1.15±0.6, p =0.01), while both DLCO/CI and DLCO/Q were higher in BB (31.32±14.1 vs. 43.84±29.5, p =0.005 and 15.84±7.5 vs. 21.93±16.2, p =0.01, respectively). CONCLUSIONS These data suggest that HF patients prescribed β‐antagonist therapy demonstrate better lung diffusion for a given cardiac output compared to HF patients not prescribed β‐antagonist therapy.

INTRODUCTION Bronchodilator therapy via β‐agonists has been considered a controversial treatment option for patients with cardiovascular disease, including heart failure (HF), due to previous studies suggesting increased rates of mortality. A major limitation to several previous studies is the lack of similar baseline characteristics between groups; therefore, a matched control comparison is yet to be explored. PURPOSE To evaluate the relationship between bronchodilator therapy and survival in HF patients. METHODS A retrospective analysis was performed on 96 HF patients who underwent a cardiopulmonary exercise test between the years 1994–2010. Patients were divided into two groups: 48 patients on bronchodilator therapy (BDT) and 48 matched controls (CTL). Patients were matched based on age (yrs), height (cm), weight (kg), body mass index (BMI), New York Heart Association (NYHA) classification, and cardioselective β‐blocker medication during the time of their cardiopulmonary exercise test. Patients were followed for an average of ten years for an endpoint of cardiovascular mortality. An independent samples t‐test was performed comparing BDT and CTL for age (yrs), height (cm), weight (kg), and BMI, to determine comparable baseline characteristics. A Chi‐Squared test compared NYHA classification, cardioselective β‐blocker status, and sex between BDT and CTL. A log rank test was performed to determine differences in survival distributions between BDT and CTL. RESULTS There were no significant demographic differences between groups (age: 59.8 vs. 60.3yrs; height: 172.1 vs. 171.9cm; weight: 86.9 vs. 86.2kg; and BMI: 28.9 vs. 28.6kg/m 2 for BDT vs. CTL, respectively). NYHA classification (χ 2 =0.00; p =1.0), cardioselective β‐blocker status (χ 2 =0.14; p =0.71) and sex (χ 2 =0.202; p =0.65) were not different between groups. BDT patients demonstrated an event rate of 51.1% compared to 42.6% for CTL patients over the same time period. The survival distribution for BDT compared to CTL was not statistically different, χ 2 (1) = 1.49, p =0.22. CONCLUSION These data suggest that HF patients on bronchodilator therapy demonstrate no significant difference in survival compared to matched HF controls. In contrast to previous work, our data suggests bronchodilator therapy does not elicit increased mortality in these HF patients.