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David Galloway Ethan Mezoff Wujuan Zhang Melissa Byrd Conrad Cole Inmaculada Aban Samuel Kocoshis Kenneth DR Setchell James E Heubi 《JPEN. Journal of parenteral and enteral nutrition》2019,43(2):263-270
Background: We determined qualitative and quantitative serum unconjugated bile acid (SUBA) levels among children with history of intestinal failure (IF) and suspected small bowel bacterial overgrowth (SBBO). Methods: This was a single‐center, case‐control pilot study conducted at Cincinnati Children's Hospital Medical Center. Children with history of IF and suspected SBBO were enrolled as subjects. Age‐matched children without IF or suspected SBBO served as controls. All participants underwent small bowel fluid sampling for microbial culture analysis. Additionally, serum fractionated and total bile acids were measured by liquid chromatography‐mass spectrometry at enrollment and following treatment for SBBO. Results: SUBA concentrations were elevated in IF subjects (median 1.16 μM, range 0.43–10.65 μM) compared with controls (median 0.10 μM, range 0.05–0.18 μM, P = 0.001). Among SUBA, chenodeoxycholic acid (CDCA) was significantly elevated in subjects (median 0.8 μM, range 0–7.08 μM) compared with controls (median 0 μM, range 0–0.03 μM, P = 0.012). When controls were excluded from analysis, IF subjects with positive aspirates for SBBO demonstrated higher concentration of CDCA (median 7.36 μM, range 1.1–8.28 μM) compared with IF subjects with negative aspirates (median 0.18 μM, range 0–1.06 μM, P = 0.017). Treatment for SBBO did not alter SUBA concentration. Conclusions: SUBA concentrations are elevated in children with history of IF and presumed SBBO compared with non‐IF controls. CDCA was more prevalent in IF subjects with positive aspirates for SBBO compared with IF subjects with negative aspirates. The determination of SUBA concentration may be a useful surrogate to small bowel fluid aspiration in the diagnosis of SBBO in children with history of IF. 相似文献
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Anca Chelariu-Raicu Alpa Nick Renata Urban Mary Gordinier Carola Leuschner Linda Bavisotto Graziela Zibetti Dal Molin John K. Whisnant Robert L. Coleman 《Gynecologic oncology》2021,160(2):418-426
ObjectiveThis randomized open-label phase II study evaluated the safety and clinical activity of EP-100 plus weekly paclitaxel in patients with recurrent ovarian cancer expressing positive LHRH receptor.MethodsIn a limited “run-in” dose escalation phase for EP-100, six patients were treated with ascending dose levels (13 mg/m2, 20 mg/m2, 30 mg/m2). In the randomized phase, patients received weekly paclitaxel (80 mg/m2 intravenously) plus twice weekly EP-100 (30 mg/m2 intravenously; combination arm) or weekly paclitaxel alone (80 mg/m2 intravenously; paclitaxel arm). The primary study endpoint was overall response rate (ORR).ResultsForty-four patients were then randomized to either the experimental combination arm (n = 23) or the standard of care paclitaxel monotherapy arm (n = 21). The ORR was 35% (95%CI 16%–57%) for the combination arm and 33% (95% CI 15%–57%) for the paclitaxel arm. An interesting observation from an unplanned analysis was that a subset of patients with target liver lesions showed a greater overall response rate to the combination (69%) compared to paclitaxel alone (16%). The frequency of treatment-related grade 3–4 adverse events was similar between treatment arms: 48% vs 43% for the combination and paclitaxel arms, respectively.ConclusionsORR in the EP-100 combination arm was similar to that in the group treated with paclitaxel alone; however, a subset of patients with liver metastases appeared to benefit from the combination. The addition of EP-100 did not appear to augment the adverse event profile of paclitaxel and was well tolerated. 相似文献
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Jean H. Siedel Kari L. Ring Wei Hu Robert L. Dood Ying Wang Keith Baggerly Kathleen M. Darcy Thomas P. Conrads Shannon Gallagher Placede Tshiaba Chris Neff Kirsten M. Timms Selanere Mangala Shannon N. Westin Russell Broaddus Gabriel Lopez-Berestein Karen H. Lu Robert L. Coleman Anil K. Sood 《Gynecologic oncology》2021,160(3):777-785
BackgroundHomologous recombination deficiency (HRD) score is related to chemotherapy response in some cancers, but its role in endometrial cancer in not known. We determined frequency and clinical significance of alterations in the HR pathway in endometrial cancer.Methods253 endometrioid endometrial adenocarcinoma (EEA) samples from two independent cohorts (discovery and replication) were tested for HRD score using the Myriad HRD assay, microsatellite instability (MSI) and tumor mutation burden (TMB) using a next generation sequencing assay. HRD scores were also generated on endometrial cancer cell lines and in vivo response to olaparib was assessed.ResultsROC curves were employed to determine optimal cutoffs of HRD in relation to survival impact in endometrial cancer and a cutoff of HRD ≥ 4 was suggested for DFS using the discovery cohort. Patients from two independent cohorts with HRD score ≥ 4 trended toward worse survival as compared to those with HRD score < 4. Both cohorts were further separated into four groups according to molecular subtypes (TMB positive; MSI positive; HRD positive; all others). When grouped by molecular subtype, there was a significant difference between groups using an HRD ≥4 cutoff in the initial (p = 0.0024) and replication (p = 0.042) cohorts. The Hec1a model (HRD score = 19) was highly sensitive to olaparib in in vitro and in vivo experiments.ConclusionsHigh HRD score was associated with worse DFS in our patient cohort. These findings suggest that HRD score may have clinical utility in patients with advanced or recurrent endometrial cancer. 相似文献
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Mark F. Zhu Katy Kim Alana Cavadino Brendan Coleman Jacob T. Munro Simon W. Young 《The Journal of arthroplasty》2021,36(1):305-310.e1
BackgroundProsthetic joint infection (PJI) is the most common cause of failure following total knee arthroplasty (TKA). This study aimed to determine the success of debridement, antibiotics, and implant retention (DAIR) in a large cohort of TKA PJIs and assess the utility of current classification systems in predicting DAIR outcomes in early postoperative, late hematogenous, and chronic PJIs.MethodsIn a multicenter review over 15 years, 230 patients underwent DAIR for first episode PJI following primary TKA. Patient demographics, disease and surgical factors, treatment regime, and outcomes were identified. Univariate and multivariate survival analyses were performed to identify factors associated with successful DAIR. Continuous variables with predictive value were further analyzed using receiver operating characteristic curves. The ability to predict DAIR outcomes of multiple classification systems was also assessed.ResultsPatients were followed for an average of 6.9 years. The overall success rate of DAIR was 53.9%. On receiver operating characteristic analysis, 3 months (area under the curve = 0.63) and 1-year age (area under the curve = 0.66) of implant cut-offs was similarly predictive of outcomes. On multivariate survival analysis, DAIR was successful in 64% of “early” PJIs (implant <1 year) vs 38% of “late hematogenous” PJIs (implant >1 year; odds ratio [OR] 1.78, P = .01). For late PJIs (implant >1 year), Staphylococcus aureus (OR 4.70, P < .001) and gram-negative infections (OR 2.56, P = .031) were risk factors for DAIR failure.ConclusionDAIR has a high failure rate in all PJIs occurring more than a year post primary TKA, particularly when caused by S aureus or gram-negative bacteria. The age of implant is an important predictor of DAIR outcomes. 相似文献
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Andrew W. Silagy MBBS BMedSc Ritesh R. Kotecha MD Stanley Weng MD Arturo Holmes MD Nirmish Singla MD Roy Mano MD Kyrollis Attalla MD Kate L. Weiss BS Renzo G. DiNatale MD MS Sujata Patil PhD Jonathan A. Coleman MD Robert J. Motzer MD Paul Russo MD Martin H. Voss MD A. Ari Hakimi MD 《Cancer》2021,127(21):3946-3956
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Craig I. Coleman Alexander G.G. Turpie Thomas J. Bunz Jan Beyer-Westendorf William L. Baker 《The American journal of medicine》2019,132(4):498-504