Citations

AbstractPatients with resectable Ewing sarcoma (ES) in select sites, such as the pelvis or chest wall, have a higher risk of positive microscopic margins following surgery. AEWS1031 was the first North American/Australasia ES cooperative group trial allowing standardized preoperative radiotherapy, intended to minimize the morbidity of combined modality local tumor control as well as improve the likelihood of clear surgical margins. In this study, we found that the use of low‐dose preoperative radiation to a smaller target volume resulted in a high rate of R0 resection. The robust pathologic response rate strengthens existing evidence illustrating the radiosensitivity of Ewing sarcoma.

ABSTRACT Pneumonia may be caused by a diverse group of microorganisms; however, a microbiologic diagnosis is not universally made. Molecular tests such as the BIOFIRE FILMARRAY Pneumonia Panel (BF-PP) offer the possibility of rapid identification of potential pneumonia pathogens. This retrospective analysis was conducted as a sub-study of a recently published randomized controlled trial. Specimens from patients with suspected pneumonia were tested by the BF-PP, with results compared to cultures. The overall BF-PP positivity rate was 44.8% (252/563), and was higher [64.6% (164/254)] in specimens from patients ultimately diagnosed with pneumonia. Discrepancies between the BF-PP and cultures were most common for Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis, and Streptococcus agalactiae . Positive percent agreement (PPA) and negative percent agreement (NPA) between the BF-PP and culture were 91.4% (CI 86.3%–94.9%) and 83.6% (CI 79.5%–87.2%), respectively. For most bacteria, a correlation between high genomic abundance (genomic copies/mL) reported from the BF-PP and culture growth abundance was found. In specimens from patients ultimately diagnosed with pneumonia, clinical consistency—assessed based on whether BF-PP results aligned with associated culture results—was 79.9% and was highest for bronchoalveolar lavage fluid specimens. The BF-PP has reliable analytical performance and offers the potential advantage over conventional cultures of providing higher detection rates and more rapid results. Interestingly, despite the use of this advanced molecular diagnostic tool, one-third of pneumonia cases remained without a microbiologic etiology. IMPORTANCE This study evaluates the BIOFIRE FILMARRAY Pneumonia Panel by comparing its performance to conventional cultures in a real-world patient population (including patients ultimately diagnosed as not having pneumonia) using different types of specimens. Findings show a higher detection rate of microorganisms with the panel compared to cultures, suggesting that this test could aid in tailoring treatments for pneumonia. However, challenges remain and require further study, including distinguishing true pathogens from colonizing microorganisms and determinig why one-third of patients diagnosed with pneumonia still lacked a microbiologic etiology.

Abstract Arthrofibrosis of the knee is a difficult‐to‐manage complication after meniscoligamentous knee injuries, traumatic injuries with articular extension, and surgeries to treat these conditions. Treatment protocols for the management of postoperative arthrofibrosis exhaust nonoperative therapies before proceeding to the operating room for lysis of adhesions (LOA). Although LOA restores range of motion in most cases, a recurrence of arthrofibrosis is possible when postoperative therapy protocols are not strictly followed. Limited treatment options exist in the setting of recalcitrant arthrofibrosis. Revision arthroscopic LOA may be performed in this scenario. This revision procedure places neurovascular anatomy in the posterior compartment at risk. Performing a posterior capsule release in the arthroscopic management of recalcitrant arthrofibrosis is challenging but important to optimize recovery of range of motion. This Technical Note and accompanying video present a stepwise approach to LOA that demonstrates a safe method for performing an arthroscopic posterior capsule release in these challenging cases. Technique Video video See video under supplementary data.

Abstract Background Cardiac troponin (cTn) levels exceeding the 99th percentile upper reference limit and a rise/fall pattern are key for diagnosing myocardial injury and infarction. Macrotroponins, formed by patient anti-cTn antibodies targeting cTn, can cause persistently elevated cTn levels without ongoing myocardial injury. The frequency and impact of macrotroponin interference on cTn 99th percentiles are unclear. This study compares sex-specific 99th percentiles for 2 cTn assays, before and after excluding macrotroponin-positive samples, focusing on the top 10% of cTn levels. Methods We examined 1058 plasma samples from healthy individuals previously used for Danish cTn 99th percentiles. Following International Federation of Clinical Chemistry and Laboratory Medicine educational recommendations, macrotroponin presence was assessed in the top 10% cTn samples using immunoglobulin G (IgG) depletion screening and a reference sucrose gradient, confirming macrotroponin when both methods concurred. Due to analytical dilution constraints, [the highest] 88 of 135 Siemens Atellica high-sensitivity cTnI (hs-cTnI) samples were analyzed with both methods. All 106 Roche hs-cTnT samples were negative using IgG depletion, and sucrose analysis was limited to the highest 70 samples. Results Macrotroponin was found in 76% (67/88) of Siemens samples but in none of the Roche samples (0/70). Excluding macrotroponin-affected samples lowered the Siemens 99th percentiles from 117 ng/L to 22 ng/L in men and from 37 ng/L to 9 ng/L in women. The 99th/50th percentile ratio for Siemens decreased from 12- to 29-fold to 3- to 7-fold, approaching the Roche ratios. Conclusions Macrotroponin significantly influenced the Siemens Atellica hs-cTnI 99th percentiles, suggesting important clinical implications that warrant further prospective studies. The 99th/50th percentile ratio may help evaluate macrotroponin interference in troponin assays.

INTRODUCTION: DeepSeek was evaluated in gastroenterology board examination performance against legacy ChatGPT offline models, which previously showed failing performance. METHODS: The performances of the DeepSeek base R1 model and search-augmented R1 model were assessed using American College of Gastroenterology self-assessments (455 questions). RESULTS: DeepSeek exceeded the passing threshold. Search-augmented DeepSeek scored 81.5% across all questions, and the R1 base model scored 77.1%. Both search-augmented and offline DeepSeek models surpassed offline ChatGPT-3 (65.1%) and ChatGPT-4 (62.4%) ( P < 0.001). DISCUSSION: DeepSeek exhibited passing performance on the gastroenterology board examination but had gaps in niche topics and image exclusion limit utility. It may supplement education if validated by specialists.

Abstract Introduction Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, multiple-cohort, open-label study (NCT05875974) assessing the effectiveness of low-sodium oxybate (LXB; Xywav®) treatment on daytime and nighttime symptoms in participants with narcolepsy (type 1 [NT1] or 2 [NT2]) or idiopathic hypersomnia. Data presented are from the narcolepsy cohort. Methods DUET included a screening period (with 2-week washout for current oxybate users), 8-day baseline (BL) period, 2- to 8-week LXB titration period, 2-week stable-dose period, 8-day end-of treatment (EOT) period, and 2-week safety follow-up. The primary endpoint was change in Epworth Sleepiness Scale (ESS) score from BL to EOT. Key secondary endpoints for the narcolepsy cohort included change in polysomnography parameters: total shifts from deeper to lighter sleep stages, stage N3 sleep duration (minutes), and number of awakenings. Additional endpoints included Patient Global Impression of Change (PGIc)–overall narcolepsy disease. Primary and key secondary endpoints were controlled for multiplicity with sequential testing; other P-values are considered nominal. Results Fifty-five narcolepsy participants enrolled and were dosed with LXB (NT1, n=26; NT2, n=29); 13 transferred to another cohort and 34 were completers (NT1, n=16; NT2, n=18). Enrolled participants were mostly female (72.7%) and White (80.0%); mean (SD) age was 33.4 (12.9) years (NT1=34.6 [12.6]; NT2=32.4 [13.2]). For completers, least-squares mean (LSM) (SE) changes in ESS score were −7.7 (0.9), P&lt;.0001, overall; NT1=−6.5 (1.4), P&lt;.0001; NT2=−8.8 (1.3), P&lt;.0001. Compared with BL, sleep architecture at EOT showed fewer deeper to lighter sleep stage shifts (LSM [SE]: −13.1 [2.9], P&lt;.0001, overall; NT1=−13.9 [4.3], P=0.0029; NT2=−12.3 [4.1], P=0.0050); increased stage N3 sleep (minutes) (45.0 [8.8], P&lt;.0001, overall; NT1=49.8 [13.0], P=0.0006; NT2=40.8 [12.3], P=0.0023); and fewer awakenings (−3.2 [0.9], P=0.0015, overall; NT1=−4.1 [1.4], P=0.0056; NT2=−2.3 [1.3], P=0.0771). Most participants (93.3%, n=30; NT1, 86.7%, n=15; NT2, 100%, n=15) reported improvement (very much, much, minimally) in overall narcolepsy disease on PGIc. Treatment-emergent adverse events were consistent with the known safety profile of LXB. Conclusion Participants with NT1 and NT2 taking open-label LXB showed improvements in daytime sleepiness (decreased ESS scores) and reduced symptom burden (improved PGIc), which paralleled improvements in sleep architecture and disruption. Support (if any) Jazz Pharmaceuticals

Abstract Introduction Introduction: Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, multiple-cohort, open-label study (NCT05875974) evaluating the effectiveness of low-sodium oxybate (LXB, Xywav®) treatment on daytime and nighttime symptoms, including excessive daytime sleepiness (EDS) and polysomnography in participants with idiopathic hypersomnia (IH) or narcolepsy. Data presented are from the IH cohort. Methods DUET included screening (with 2-week washout for oxybate users), 8-day baseline (BL), 2- to 8-week LXB titration, 2-week stable-dose, 8-day end-of-treatment (EOT), and 2-week safety follow-up periods. The primary endpoint was change in Epworth Sleepiness Scale (ESS) score from BL to EOT. Secondary endpoints for the IH cohort included change in Idiopathic Hypersomnia Severity Scale (IHSS) total score, Patient Global Impression of Change (PGIc)−overall IH disease, PGIc−sleep inertia, and Patient Global Impression of Severity (PGIs)−sleep inertia. Exploratory endpoints included IHSS component scores (daytime functioning, sleep inertia). Primary and key secondary (IHSS total score) endpoints were controlled for multiplicity with sequential testing; all other P-values are considered nominal. Results Forty-six people with IH enrolled and were dosed with LXB; 40 were completers. Enrolled participants were mostly female (80.4%) and White (84.8%), with a mean (SD) age of 38.1 (11.8) years. For completers, BL mean (SD) ESS score and IHSS total score were 16.5 (2.7) and 32.9 (7.1), respectively; least-squares mean (LSM) (SE) changes from BL to EOT were −8.4 (0.7), P&lt;.0001 and −15.5 (1.5), P&lt;.0001. BL mean (SD) IHSS component scores for daytime functioning and sleep inertia were 17.7 (4.2) and 10.7 (3.1), respectively; LSM (SE) changes from BL to EOT were −8.8 (1.0), P&lt;.0001 and −4.8 (0.4), P&lt;.0001. At EOT, most participants reported improvement (very much, much, minimally) on PGIc−overall IH disease (94.6%) and PGIc−sleep inertia (81.1%). At BL, 25.0% of participants reported sleep inertia severity as very mild/mild/not present on PGIs–sleep inertia vs 59.0% at EOT. Treatment-emergent adverse events were consistent with the known safety profile of LXB. Conclusion People with IH taking open-label LXB showed improvements in EDS and sleep inertia (decreased ESS and IHSS component scores) and reported reduced multi-symptom burden (decreased IHSS total scores and improved PGIc/PGIs ratings). Support (if any) Jazz Pharmaceuticals

Abstract Introduction Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, multiple-cohort, open-label study (NCT05875974) evaluating effectiveness of low-sodium oxybate (LXB, Xywav®) treatment on outcomes including polysomnography (PSG)-based sleep architecture in participants with idiopathic hypersomnia or narcolepsy (type 1 [NT1] or 2 [NT2]). Methods DUET included a screening period (2-week washout for current oxybate users), 8-day baseline (BL) period, 2- to 8-week LXB titration period, 2-week stable-dose period (SDP), 8-day end-of-treatment period (EOT), and 2-week safety follow-up. Participants underwent nocturnal PSG (ad libitum protocol) at BL and EOT. PSGs were scheduled to allow a minimum of 10 hours in bed, unless the participant naturally awakened earlier; bedtime was determined by habitual bedtime. PSG recordings were centrally scored. Data were analyzed for participants in the narcolepsy cohort completer set. Total shifts from deeper to lighter sleep stages was defined as N1/N2/N3/REM to wake and N2/N3/REM to N1. Key secondary endpoints (total stage shifts, N3 duration) were controlled for multiplicity with sequential testing; other P-values are considered nominal. Results Fifty-five participants with narcolepsy enrolled (NT1, n=26; NT2, n=29); 34 completed the study (NT1, n=16; NT2, n=18). Most were female (73%) and White (80%) (mean±SD age, 33.4±12.9 years). Mean±SD total sleep time (TST) at BL/EOT was 453.2±80.1/452.4±70.0 minutes (LSM change [95% CI]: –0.78 [–23.7, 22.1]; P=.9451). Mean±SD number of total shifts from deeper to lighter sleep stages at BL/EOT was 54.6±28.0/41.6±25.6 (LSM [95% CI]: –13.1 [–19.0, –7.1]; P&lt;.0001 [controlled for multiplicity]). Mean±SD time spent in N1 at BL/EOT was 45.3±28.4/37.2±25.2 minutes (LSM [95% CI]: –8.1 [–14.9, –1.4]; P=.0196), % of stage was 10.4%/8.2% (P=.0037); in N2 was 241.8±61.2/243.3±76.1 minutes (LSM [95% CI]: 1.5 [–23.6, 26.6]; P=.9040), 53.1%/53.2% (P=.9869); in N3 was 61.1±34.8/106.1±69.5 minutes (LSM [95% CI]: 45.0 [27.0, 63.0]; P&lt;.0001 [controlled for multiplicity]), 13.7%/24.0% (P&lt;.0001); and in REM was 105.0±42.7/65.8±33.1 minutes (LSM [95% CI]: –39.2 [–50.8, –27.5]; P&lt;.0001), 22.8%/14.7% (P&lt;.0001). Conclusion Participants with narcolepsy taking open-label LXB showed negligible change in TST and N2, increased N3, decreased N1 and REM, and fewer shifts from deeper to lighter stages of sleep. Support (if any) Jazz Pharmaceuticals

AbstractObjectivesChildren with inflammatory bowel disease (IBD) often have low body mass index (BMI). BMI does not distinguish between fat and lean mass. Body composition deficits may be associated with worse clinical outcomes. We examined the prevalence of risk factors associated with body composition deficits in youth with pediatric‐onset IBD, and factors associated with low lean mass in the presence of a normal BMI Z‐score (BMI‐Z).MethodsNewly diagnosed IBD patients ages 5–20 years with whole body dual energy x‐ray absorptiometry scans acquired between 2014 and 2019 were included. Appendicular lean soft tissue mass index (AppLSTMI) and fat mass index (FMI) were expressed as age and sex‐specific Z‐scores. Clinical and demographic data were collected retrospectively. Logistic regression was used to assess associations with body composition outcomes.ResultsFive hundred sixteen patients were included, 26% had AppLSTMI Z‐score (AppLSTMI‐Z) < −2, 4% had BMI‐Z < −2, and none had FMI Z‐score (FMI‐Z) < −2. Increased risk of low AppLSTMI‐Z associated with Crohn's diagnosis, Asian ethnicity, disease activity, elevated platelets, and glucocorticoid use. Females had lower FMI‐Z. Low AppLSTMI‐Z within the context of BMI‐Z (n = 112) was associated with Crohn's disease, Asian (odds ratio [OR] = 3.77, p = 0.001) and Black identity (OR = 0.32, p = 0.02), and elevated platelets (OR = 1.76, p = 0.02) compared to those with normal BMI‐Z and normal AppLSTMI‐Z.ConclusionsBMI is a poor indicator of body composition in children with IBD as it masks lean mass deficits which are highly prevalent. Future studies regarding the long‐term consequences and reversibility of this deficit are warranted.