Publications by authors named "Jingxia Liu"

150 Publications

A cluster randomized stepped-wedge trial to de-implement unnecessary post-operative antibiotics in children: the optimizing perioperative antibiotic in children (OPerAtiC) trial.

Implement Sci 2021 Mar 19;16(1):29. Epub 2021 Mar 19.

Division of Pediatric Infectious Diseases, Department of Pediatrics, Washington University in St. Louis School of Medicine, Campus Box 8116, 660 S. Euclid Ave, St. Louis, MO, 63110, USA.

Background: Antibiotic-resistant infections have become a public health crisis that is driven by the inappropriate use of antibiotics. In the USA, antibiotic stewardship programs (ASP) have been established and are required by regulatory agencies to help combat the problem of antibiotic resistance. Post-operative antibiotic use in surgical cases deemed low-risk for infection is an area with significant overuse of antibiotics in children. Consensus among leading public health organizations has led to guidelines eliminating post-operative antibiotics in low-risk surgeries. However, the best strategies to de-implement these inappropriate antibiotics in this setting are unknown.

Methods/design: A 3-year stepped wedge cluster randomized trial will be conducted at nine US Children's Hospitals to assess the impact of two de-implementation strategies, order set change and facilitation training, on inappropriate post-operative antibiotic prescribing in low risk (i.e., clean and clean-contaminated) surgical cases. The facilitation training will amplify order set changes and will involve a 2-day workshop with antibiotic stewardship teams. This training will be led by an implementation scientist expert (VRM) and a pediatric infectious diseases physician with antibiotic stewardship expertise (JGN). The primary clinical outcome will be the percentage of surgical cases receiving unnecessary post-operative antibiotics. Secondary clinical outcomes will include the rate of surgical site infections and the rate of Clostridioides difficile infections, a common negative consequence of antibiotic use. Monthly semi-structured interviews at each hospital will assess the implementation process of the two strategies. The primary implementation outcome is penetration, which will be defined as the number of order sets changed or developed by each hospital during the study. Additional implementation outcomes will include the ASP team members' assessment of the acceptability, appropriateness, and feasibility of each strategy while they are being implemented.

Discussion: This study will provide important information on the impact of two potential strategies to de-implement unnecessary post-operative antibiotic use in children while assessing important clinical outcomes. As more unnecessary medical practices are identified, de-implementation strategies, including facilitation, need to be rigorously evaluated. Along with this study, other rigorously designed studies evaluating additional strategies are needed to further advance the burgeoning field of de-implementation.

Trial Registration: NCT04366440. Registered April 28, 2020, https://clinicaltrials.gov/ct2/show/NCT04366440 .
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http://dx.doi.org/10.1186/s13012-021-01096-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980649PMC
March 2021

Vorolanib (X-82), an oral anti-VEGFR/PDGFR/CSF1R tyrosine kinase inhibitor, with everolimus in solid tumors: results of a phase I study.

Invest New Drugs 2021 Mar 18. Epub 2021 Mar 18.

Division of Oncology, Washington University, St. Louis, MO, USA.

Background Anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) combined with mTOR inhibitors, like everolimus, result in significant responses and prolonged progression-free survival (PFS) among patients with renal cell carcinoma (RCC) [1]. However, everolimus doses >5 mg are often not tolerated when combined with other TKIs. Vorolanib (X-82), an oral anti-VEGFR/platelet derived growth factor receptor (PDGFR)/colony stimulating factor 1 receptor (CSF1R) multitarget TKI, has a short half-life and limited tissue accumulation. We conducted a Phase 1 study of vorolanib with everolimus (10 mg daily) in patients with solid tumors. Methods A 3 + 3 dose escalation design was utilized to determine dose limiting toxicities (DLT) and recommended Phase 2 dose (RP2D) of vorolanib/everolimus. Oral vorolanib at 100, 150, 200, 300, or 400 mg was combined with 10 mg oral everolimus daily. The phase 2 portion was terminated after enrolling two patients due to funding. Results Eighteen patients were evaluable for DLT among 22 treated subjects. Observed DLTs were grade 3 fatigue, hypophosphatemia, and mucositis. The RP2D is vorolanib 300 mg with everolimus 10 mg daily. In 15 patients evaluable for response, three had partial response (PR; 2 RCC, 1 neuroendocrine tumor [NET]) and eight had stable disease (SD; 2 RCC, 6 NET). Conclusions Vorolanib can safely be combined with everolimus. Encouraging activity is seen in RCC and NET. Further studies are warranted. Trial Registration Number: NCT01784861.
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http://dx.doi.org/10.1007/s10637-021-01093-7DOI Listing
March 2021

nab-Paclitaxel and cisplatin followed by cisplatin and radiation (Arm 1) and nab-paclitaxel followed by cetuximab and radiation (Arm 2) for locally advanced head and neck squamous-cell carcinoma: a multicenter, non-randomized phase 2 trial.

Med Oncol 2021 Mar 8;38(4):35. Epub 2021 Mar 8.

Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.

In locally advanced head and neck squamous-cell carcinoma (LA-HNSCC), clinical complete response (cCR) at the primary site, assessed by clinical examination, after induction chemotherapy predicts for a low relapse risk after subsequent chemoradiotherapy. Prior studies showed a cCR rate of 77% with induction nanoparticle albumin-bound (nab)-paclitaxel given with cisplatin and 5-fluorouracil (APF). The primary aims of this non-randomized phase 2 trial were to determine the cCR rate after induction nab-paclitaxel and cisplatin (Arm 1) and after nab-paclitaxel monotherapy (Arm 2). Eligibility required LA-HNSCC, T2-T4 stage classification, and suitable (Arm 1) or unsuitable (Arm 2) candidates for cisplatin. Arm 1 patients received nab-paclitaxel and cisplatin, then cisplatin with radiation. Arm 2 patients received nab-paclitaxel, then cetuximab with radiation. The primary endpoint was cCR after two cycles of induction chemotherapy. Each arm enrolled forty patients. cCR at the primary site occurred in 28 patients (70%) after nab-paclitaxel and cisplatin and in 8 patients (20%) after nab-paclitaxel monotherapy. The overall clinical response rate was 98% after nab-paclitaxel and cisplatin and 90% after nab-paclitaxel monotherapy. In subset analyses, cCR rates by T stage classifications (T2, T3, T4) were 54, 86, and 69% after nab-paclitaxel and cisplatin, and 14, 11, and 26% after nab-paclitaxel. cCR rates by human papillomavirus status (p16 positive oropharynx vs other) were 72 and 64% after nab-paclitaxel and cisplatin and 35 and 9% after nab-paclitaxel. The cCR rate after nab-paclitaxel and cisplatin was similar to APF; however, the cCR rate after nab-paclitaxel monotherapy was lower. The trial was registered at ClinicalTrials.gov NCT02573493 on October 9, 2015.
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http://dx.doi.org/10.1007/s12032-021-01479-wDOI Listing
March 2021

Obese endometrial cancer survivors' perceptions of weight loss strategies and characteristics that may influence participation in behavioral interventions.

Gynecol Oncol Rep 2021 May 8;36:100719. Epub 2021 Feb 8.

Division of Gynecologic Oncology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.

We aimed to evaluate obese endometrial cancer (EC) survivors' perceptions of weight loss barriers and previously attempted weight loss methods and to identify characteristics that predicted willingness to enroll in a behavioral intervention trial. We administered a 27-question baseline survey at an academic institution to EC survivors with body mass index ≥ 30 kg/m. Survivors were asked about their lifestyles, previous weight loss attempts, perceived barriers, and were offered enrollment into an intervention trial. Data was analyzed using Fisher's Exact, Kruskal-Wallis, and univariate and multivariate regressions. 155 of 358 (43%) eligible obese EC survivors were surveyed. Nearly all (n = 148, 96%) had considered losing weight, and 77% (n = 120) had tried two or more strategies. Few had undergone bariatric surgery (n = 5, 3%), psychologic counseling (n = 2, 1%), or met with physical therapists (n = 9, 6%). Lower income was associated with difficulty in accessing interventions. Survivors commented that negative self-perceptions and difficulties with follow-through were barriers to weight loss, and fear of complications and self-perceived lack of qualification were deterrents to bariatric surgery. 80 (52%) of those surveyed enrolled in the trial. In a multivariate model, adjusting for race and stage, survivors without recurrence were 4.3 times more likely to enroll than those with recurrence. Most obese EC survivors have tried multiple strategies to lose weight, but remain interested in weight loss interventions, especially women who have never experienced recurrence. Providers should encourage weight loss interventions early, at the time of initial diagnosis, and promote underutilized strategies such as psychological counseling, physical therapy, and bariatric surgery.
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http://dx.doi.org/10.1016/j.gore.2021.100719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907756PMC
May 2021

Addressing Unmet Basic Needs to Improve Colposcopy Adherence Among Women With Abnormal Cervical Cancer Screening.

J Low Genit Tract Dis 2021 Apr;25(2):106-112

Health Communication Research Laboratory, The Brown School, Washington University in St Louis, St Louis, MO.

Objectives: The aims of the study were to identify unmet basic needs (BNs) among women referred to colposcopy, to assess patient acceptability/satisfaction with assistance from a navigator to address unmet BNs, and to estimate adherence to colposcopy.

Methods: Women were recruited between September 2017 and January 2019 from 2 academic colposcopy centers, one serving a rural and one an urban area. Basic needs were assessed by phone before colposcopy appointments and considered unmet if unlikely to resolve in 1 month. Colposcopy adherence prestudy and poststudy implementation was abstracted over 4-6 months from administrative records. After a lead-in phase of 25 patients at each site, a BN navigator was offered to new participants with 1 or more unmet BNs. Primary outcome was adherence to initial appointment.

Results: Among 100 women, 59% had 1 or more unmet BNs, with similar prevalence between urban and rural sites. Adherence to initial colposcopy was 83% overall, 72% at the rural clinic, and 94% at the urban clinic (p = .006). These adherence rates were improved from 4 months before study launch (30/59 [51%] rural clinic and 68/137 [50%] urban clinic). Although acceptability of BN navigation was greater than 96% and women felt that it helped them get to their colposcopy visit, having a navigator was not associated with adherence. Women reporting no unmet BNs had the lowest adherence compared with women with 1 or more unmet BNs, regardless of navigator assistance (p = .03).

Conclusions: Disadvantaged women who need colposcopy have unmet BNs and value navigator assistance for initial appointments. However, when appointment scheduling includes telephone reminders and inquiring about BNs, a navigator may not add value.
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http://dx.doi.org/10.1097/LGT.0000000000000593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987876PMC
April 2021

Nanoparticle albumin-bound paclitaxel with cetuximab and carboplatin as first-line therapy for recurrent or metastatic head and neck cancer: A single-arm, multicenter, phase 2 trial.

Oral Oncol 2021 Apr 3;115:105173. Epub 2021 Feb 3.

Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States; Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, United States.

Objectives: Macropinocytosis promotes internalization of albumin into cells to serve as a nutrient supply and is constitutively driven by signaling pathways frequently hyperactivated in head and neck squamous-cell carcinoma (HNSCC). In this way, drugs bound to albumin may selectively target HNSCC. nab-paclitaxel is a nanoparticle albumin-bound formulation of paclitaxel that improves drug delivery into tumor compared to paclitaxel. The primary aim of this single-arm, multicenter, phase 2 trial was to determine if nab-paclitaxel, cetuximab, and carboplatin (CACTUX regimen) would result in longer progression-free survival (PFS) than the historical regimen (EXTREME: 5-fluorouracil, cetuximab, and a platinum).

Materials And Methods: Patients with untreated recurrent or metastatic HNSCC received six, three-week cycles of nab-paclitaxel, cetuximab, and carboplatin, followed by maintenance nab-paclitaxel and cetuximab until progression. We hypothesized the median PFS with CACTUX would be 35% longer than with EXTREME (corresponding to 7.6 vs 5.6 months; power 0.80, α = 0.05, one-sided test, n = 70). Secondary outcomes included objective response rate (ORR) and overall survival (OS).

Results: Seventy-four patients enrolled into the trial; seventy were evaluable. The median PFS was 6.1 months (95% CI, 4.1-7.4). The ORR was 60%. Median follow-up was 18 months (IQR: 4.7-23). The median OS was 17.8 months (95% CI, 8.5-21.7) for all patients, and 19.8 months (95% CI, 10.9-22.0) for human papillomavirus (HPV)-related oropharynx SCC and 14.0 months (95% CI, 4.6-23.3) for HPV-unrelated HNSCC.

Conclusion: Among patients with recurrent or metastatic HNSCC, CACTUX did not result in a longer PFS than historical EXTREME. However, CACTUX did result in a more favorable ORR and OS.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105173DOI Listing
April 2021

Clinical Outcomes of Lung Transplants From Donors With Unexpected Pulmonary Embolism.

Ann Thorac Surg 2020 Oct 22. Epub 2020 Oct 22.

Division of Cardiothoracic Surgery, Department of Surgery, Washington University, Saint Louis, Missouri. Electronic address:

Background: Pulmonary embolism (PE) is unexpectedly detected in some donor lungs during organ procurement for lung transplantation. Anecdotally, such lungs are usually implanted; however, the impact of this finding on recipient outcomes remains unclear. We hypothesized that incidentally detected donor PE is associated with adverse short-term and long-term outcomes among lung transplant recipients.

Methods: We analyzed a prospectively maintained database of all lung donors procured by a single surgeon and transplanted at our institution between 2009 and 2018. A standardized approach was used for all procurements and included antegrade and retrograde flush. Pulmonary embolism was defined as macroscopic thrombus seen in the pulmonary artery during the donor procurement operation.

Results: A total of 501 consecutive lung procurements were performed during the study period. The incidence of donor PE was 4.4% (22 of 501). No organs were discarded owing to PE. Donors with PE were similar to donors without PE in baseline characteristics and Pao. Recipients in the two groups were also similar. Pulmonary embolism was associated with a higher likelihood of acute cellular rejection grade 2 or more (10 of 22 [45.5%] vs 120 of 479 [25.1%], P = .03). Multivariable Cox modeling demonstrated an association between PE and the development of chronic lung allograft dysfunction (hazard ratio 2.02; 95% confidence interval, 1.23 to 3.30; P = .005).

Conclusions: Lungs from donors with incidentally detected PE may be associated with a higher incidence of recipient acute cellular rejection as well as reduced chronic lung allograft dysfunction-free survival. Surgeons must use caution when transplanting lungs with incidentally discovered PE. These preliminary findings warrant corroboration in larger data sets.
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http://dx.doi.org/10.1016/j.athoracsur.2020.08.040DOI Listing
October 2020

Palbociclib and cetuximab in cetuximab-resistant human papillomavirus-related oropharynx squamous-cell carcinoma: A multicenter phase 2 trial.

Oral Oncol 2021 Mar 16;114:105164. Epub 2021 Jan 16.

Division of Medical Oncology and Alvin J Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States. Electronic address:

Objectives: We previously reported that palbociclib, a selective CDK4/6 inhibitor, given with cetuximab, resulted in an objective response rate (ORR) of 19% in cetuximab-resistant human papillomavirus (HPV)-unrelated head and neck squamous-cell carcinoma (HNSCC). In this study, we aimed to determine the proportion of patients with cetuximab-resistant HPV-related oropharynx (OP)SCC who achieved an objective response to palbociclib and cetuximab.

Materials And Methods: We performed a multicenter phase 2 trial. Key eligibility requirements included measurable HPV-related OPSCC that progressed on a cetuximab-containing regimen. Palbociclib 125 mg po was administered on Days 1-21 of 28 day cycles, with weekly cetuximab. The primary endpoint was objective response (RECIST1.1). The study design had a probability of 0.70 of accepting the alternative hypothesis (ORR ≥ 20%) and rejecting the null hypothesis (ORR ≤ 5%). Two or more tumor responses among 24 patients were needed to accept the alternative hypothesis.

Results: Twenty-four patients enrolled. The median interval from prior cetuximab to study enrollment was 0.7 months (IQR 0.2-6.1). Disease progression on a platinum agent occurred in 23 patients (96%). An objective response occurred in one patient (ORR 4%). The duration of response was 4 months. Stable disease with ≥ 10% decrease in target lesions occurred in 2 patients (8%). Median follow-up was 8.9 (IQR 3.7-16.8) months. The median progression-free survival was 1.9 months (95% CI 1.8-2.1) and the median overall survival was 17.1 months (95%CI: 5.8-21.5).

Conclusion: The trial did not meet its primary endpoint. Further investigation of palbociclib and cetuximab in cetuximab-resistant HPV-related OPSCC is not warranted.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105164DOI Listing
March 2021

Obesity and White Matter Neuroinflammation Related Edema in Alzheimer's Disease Dementia Biomarker Negative Cognitively Normal Individuals.

J Alzheimers Dis 2021 ;79(4):1801-1811

Mallinckrodt Institute of Radiology, Division of Neuroradiology, Washington University in St. Louis, St. Louis, MO, USA.

Background: Obesity is related to quantitative neuroimaging abnormalities including reduced gray matter volumes and impaired white matter microstructural integrity, although the underlying mechanisms are not well understood.

Objective: We assessed influence of obesity on neuroinflammation imaging that may mediate brain morphometric changes. Establishing the role of neuroinflammation in obesity will enhance understanding of this modifiable disorder as a risk factor for Alzheimer's disease (AD) dementia.

Methods: We analyzed brain MRIs from 104 cognitively normal participants (CDR = 0) and biomarker negativity for CSF amyloid or tau. We classified body mass index (BMI) as normal (BMI <25, N = 62) or overweight and obese (BMI ≥25, N = 42). Blood pressure was measured. BMI and blood pressure classifications were related to neuroinflammation imaging (NII) derived edema fraction in 17 white matter tracts. This metric was also correlated to hippocampal volumes and CSF biomarkers of inflammation and neurodegeneration: YKL-40, SNAP25, VILIP, tau, and NFL.

Results: Participants with BMI <25 had lower NII-derived edema fraction, with protective effects of normal blood pressure. Statistically significant white matter tracts included the internal capsule, external capsule, and corona radiata, FDR correc-ted for multiple comparisons to alpha = 0.05. Higher NII-derived edema fractions in the internal capsule, corpus callosum, gyrus, and superior fronto-occipital fasciculus were related with smaller hippocampal volumes only in individuals with BMI ≥25. There were no statistically significant correlations between NII-derived edema fraction and CSF biomarkers.

Conclusion: We demonstrate statistically significant relationships between neuroinflammation, elevated BMI, and hippocampal volume, raising implications for neuroinflammation mechanisms of obesity-related brain dysfunction in cognitively normal elderly.
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http://dx.doi.org/10.3233/JAD-201242DOI Listing
January 2021

Thunderbeat™ Integrated Bipolar and Ultrasonic Forceps in the Whipple Procedure: A Prospective Randomized Trial.

Mo Med 2020 Nov-Dec;117(6):559-562

Associate Professor of Surgery, Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.

Thunderbeat™ is a device that uses both ultrasonic and advanced bipolar energies to achieve hemostasis. It has been evaluated in a variety of clinical contexts, but no literature exists regarding its application to pancreatic surgery. Using a prospective, randomized controlled trial, we evaluated its safety and efficacy in the Whipple procedure. Thirty-two participants were enrolled in the study. The Thunderbeat™ device during the Whipple procedure showed similar safety profile compared to standard of care.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721432PMC
December 2020

Donor management using a specialized donor care facility is associated with higher organ utilization from drug overdose donors.

Clin Transplant 2021 Mar 14;35(3):e14178. Epub 2020 Dec 14.

Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Saint Louis, MO, USA.

Drug overdoses have tripled in the United States over the last two decades. With the increasing demand for donor organs, one potential consequence of the opioid epidemic may be an increase in suitable donor organs. Unfortunately, organs from donors dying of drug overdose have poorer utilization rates than other groups of brain-dead donors, largely due to physician and recipient concerns about viral disease transmission. During the study period of 2011 to 2016, drug overdose donors (DODs) account for an increasingly greater proportion of the national donor pool. We show that a novel model of donor care, known as specialized donor care facility (SDCF), is associated with an increase in organ utilization from DODs compared to the conventional model of hospital-based donor care. This is likely related to the close relationship of the SDCF with the transplant centers, leading to improved communication and highly efficient donor care.
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http://dx.doi.org/10.1111/ctr.14178DOI Listing
March 2021

Rapid Administration of Ketamine for Abscess Drainage in Children-A Dose Finding Study.

Pediatr Emerg Care 2020 Dec;36(12):e671-e676

From the Division of Emergency Medicine, Department of Pediatrics, Medical college of Wisconsin.

Study Objective: To estimate the minimum dose and total sedation time of rapidly infused ketamine that achieves 3 to 5 minutes of effective sedation in children undergoing abscess incision and drainage in the emergency department.

Methods: The Up-Down method was used to estimate the dose of intravenous ketamine infused over 5 seconds or less that provided effective sedation in 50% (ED50) and 95% (ED95) for healthy children aged 2 to 5 years and 6 to 11 years undergoing abscess incision and drainage. None were pretreated with opioids. Three investigators blinded to ketamine dose independently graded sedation effectiveness by viewing a video recording of the first 5 minutes of sedation. Recovery was determined when patients reached a Modified Aldrete score of 10.

Results: We enrolled 20 children in each age group. The estimated ED50 was 0.9 and 0.6 mg/kg for the 2 to 5 years and 6 to 11 years' groups and the estimated ED95 was 1.1 mg/kg for both groups. The median time to full recovery for the 2 groups was 20.5 and 17.5 minutes when only 1 dose of ketamine was administered and 27.5 and 35 minutes when additional doses of ketamine were administered. No participants experienced serious adverse events.

Conclusions: We estimated ED50 and ED95 for rapidly infused ketamine for 2 age groups undergoing abscess incision and drainage. Further studies are needed to get a more precise estimate of ED95. The total sedation time with this technique in the abscess group was shorter than most previous studies and is consistent with our previous observations in patients undergoing fracture reduction.
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http://dx.doi.org/10.1097/PEC.0000000000002281DOI Listing
December 2020

Seed-specific expression of TaYUC10 significantly increases auxin and protein content in wheat seeds.

Plant Cell Rep 2021 Feb 11;40(2):301-314. Epub 2020 Nov 11.

State Key Laboratory of Crop Biology, Shandong Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, Tai'an, 271018, China.

Key Message: Present study revealed that specific expression of TaYUC10.3 in wheat young seeds could increase the content of auxin, and protein. Auxin is a vital endogenous hormone in plants, which is involved in the regulation of various physiological and biochemical processes in plants. The flavin-containing monooxygenase encoded by the YUCCA gene is a rate-limiting enzyme in the tryptophan-dependent pathway of auxin synthesis. TaYUC10.3 was identified, cloned and found that it was abundantly expressed in wheat young seeds. In this study, a seed-specific expression vector of TaYUC10.3 was constructed with the promoter of 1Bx17 glutenin subunit gene and transformed wheat using the particle bombardment method. The quantitative RT-PCR showed that TaYUC10.3 was expressed in a large amount in young seeds of the transgenic lines. Plant hormone-targeted metabolomics showed that the auxin content of the transgenic lines was significantly increased compared with controls. The GC / MS non-targeted metabolite multiple statistical analyses showed that the variable importance in projection (VIP) of tryptophan reduced in the transgenic lines. Simultaneously, the VIP of indole acetic acid increased. The precursor amino acids for synthesizing some proteins and carbohydrates were upregulated in the transgenic lines. Subsequently, it was found that the protein content of the seeds of the transgenic TaYUC10.3 wheat was significantly higher than that of the control. The wet gluten content and sedimentation value of the transgenic TaYUC10.3 wheat were also high. This result indicated that TaYUC10.3 might participate in auxin synthesis and affects the protein content of wheat seeds.
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http://dx.doi.org/10.1007/s00299-020-02631-yDOI Listing
February 2021

Urban-Rural Disparities in Access to Low-Dose Computed Tomography Lung Cancer Screening in Missouri and Illinois.

Prev Chronic Dis 2020 11 5;17:E140. Epub 2020 Nov 5.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Introduction: Low-dose computed tomography (LDCT) lung cancer screening is recommended for current and former smokers who meet eligibility criteria. Few studies have quantitatively examined disparities in access to LDCT screening. The objective of this study was to examine relationships between 1) rurality, sociodemographic characteristics, and access to LDCT lung cancer screening and 2) screening access and lung cancer mortality.

Methods: We used census block group and county-level data from Missouri and Illinois. We defined access to screening as presence of an accredited screening center within 30 miles of residence as of May 2019. We used mixed-effects logistic models for screening access and county-level multiple linear regression models for lung cancer mortality.

Results: Approximately 97.6% of metropolitan residents had access to screening, compared with 41.0% of nonmetropolitan residents. After controlling for sociodemographic characteristics, the odds of having access to screening in rural areas were 17% of the odds in metropolitan areas (95% CI, 12%-26%). We observed no association between screening access and lung cancer mortality. Southeastern Missouri, a rural and impoverished area, had low levels of screening access, high smoking prevalence, and high lung cancer mortality.

Conclusion: Although access to LDCT is lower in rural areas than in urban areas, lung cancer mortality in rural residents is multifactorial and cannot be explained by access alone. Targeted efforts to implement rural LDCT screening could reduce geographic disparities in access, although further research is needed to understand how increased access to screening could affect uptake and rural disparities in lung cancer mortality.
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http://dx.doi.org/10.5888/pcd17.200202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665516PMC
November 2020

Impact of Nighttime Lung Transplantation on Outcomes and Costs.

Ann Thorac Surg 2020 Oct 13. Epub 2020 Oct 13.

Department of Surgery, Division of Cardiothoracic Surgery, Washington University, St Louis, Missouri. Electronic address:

Background: Previous studies in the field of organ transplantation have shown a possible association between nighttime surgery and adverse outcomes. We aim to determine the impact of nighttime lung transplantation on postoperative outcomes, long-term survival, and overall cost.

Methods: We performed a single-center retrospective cohort analysis of adult lung transplant recipients who underwent transplantation between January 2006 and December 2017. Data were extracted from our institutional Lung Transplant Registry and Mid-America Transplant services database. Patients were classified into 2 strata, daytime (5 AM to 6 PM) and nighttime (6 PM to 5 AM), based on time of incision. Major postoperative adverse events, 5-year overall survival, and 5-year bronchiolitis obliterans syndrome-free survival were examined after propensity score matching. Additionally we compared overall cost of transplantation between nighttime and daytime groups.

Results: Of the 740 patients included in this study, 549 (74.2%) underwent daytime transplantation and 191 (25.8%) underwent nighttime transplantation (NT). Propensity score matching yielded 187 matched pairs. NT was associated with a higher risk of having any major postoperative adverse event (adjusted odds ratio, 1.731; 95% confidence interval, 1.093-2.741; P = .019), decreased 5-year overall survival (adjusted hazard ratio, 1.798; 95% confidence interval, 1.079-2.995; P = .024), and decreased 5-year bronchiolitis obliterans syndrome-free survival (adjusted hazard ratio, 1.556; 95% confidence interval, 1.098-2.205; P = .013) in doubly robust multivariable analyses after propensity score matching. Overall cost for NT and daytime transplantation was similar.

Conclusions: NT was associated with a higher risk of major postoperative adverse events, decreased 5-year overall survival, and decreased 5-year bronchiolitis obliterans syndrome-free survival. Our findings suggest potential benefits of delaying NT to daytime transplantation.
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http://dx.doi.org/10.1016/j.athoracsur.2020.07.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041913PMC
October 2020

Complex in Personal Care Products: Molecular Epidemiology and Susceptibility to Preservatives.

J Cosmet Sci 2020 May/Jun;71(3):133-148

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Detection Center of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510070, People's Republic of China (X.W., X.X., S.Z., T.S., J.L., W.L.).

Many outbreaks of complex (Bcc) infections are associated with contaminations in personal care products (PCPs). This study aimed to analyze a collection of Bcc isolates in PCPs and assess the susceptibility of preservatives, including dimethoxy dimethyl hydantoin (DMDMH), methylisothiazolinone-chloromethylisothiazolinone (MIT/cMIT), and methyl 4-hydroxybenzoate (MH). The Bcc isolates collected during the 3-year (2015-2017) study period were further examined by biochemical identification system, phylogenetic analysis based on nucleotide sequences, and multilocus sequence typing analysis. Preservatives susceptibility testing of Bcc bacteria were evaluated by minimum inhibitory concentration and minimum bactericidal concentration. A total of seven distinct sequence types (STs) were identified, which belonged to four different Bcc species: (ST621, ST258, and novel ST), (ST339 and ST336), (ST482), (ST922). For DMDMH and MH, the maximum permitted concentrations according to the safety specification of cosmetics (0.6% and 0.4%) were able to inhibit or kill all Bcc strains, but 40% of Bcc isolates could survive at higher than maximum permitted concentrations of MIT/cMIT (of a mixture in the ratio 3:1 of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one). The PCPs contamination of Bcc strains should be given more attention by manufacturers because of its diversity in molecular epidemiology and its low susceptibility to preservatives such as MIT/cMIT.
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December 2020

Re-defining a high volume center for pancreaticoduodenectomy.

HPB (Oxford) 2020 Sep 26. Epub 2020 Sep 26.

Department of Surgery, Washington University in Saint Louis, USA; Division of Hepatobiliary & Pancreatic Surgery, Washington University in Saint Louis, USA.

Background: The purpose of this study was to re-evaluate the previously utilized definitions of high volume center for pancreaticoduodenectomy to determine/establish an objective, evidence based threshold of hospital volume associated with improvement in perioperative mortality.

Methods: Patients who underwent pancreaticoduodenectomy were identified using the National Cancer Database from 2004 to 2015. The relationship between hospital volume and 90-day mortality was assessed using a logistic regression model. Receiver Operator Characteristic analysis was performed and Youden's statistic was utilized to calculate the optimal cut offs.

Results: 42,402 patients underwent elective Pancreaticoduodenectomy at 1238 unique hospitals. A logistic regression was performed which showed a significant inverse linear association between institutional volume and overall 90 day mortality. The maximum improvement in 90 day mortality is seen if the average annual hospital volume was greater than 9 (OR = 0.647 (0.595-0.702), p < 0.0001). When analysis is limited to hospitals that performed >9 cases per year, the maximum improvement in 90 day mortality was noticed at 36 cases per year (OR = 0.458 (0.399-0.525), p < 0.0001).

Conclusions: Based on our results, we recommend defining low, medium, and high volume centers for pancreaticoduodenectomy as hospitals with average annual volume less than 9, 9 to 35, and more than 35 cases per year, respectively.
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http://dx.doi.org/10.1016/j.hpb.2020.09.009DOI Listing
September 2020

Adenoma-like adenocarcinoma: clinicopathologic characterization of a newly recognized subtype of colorectal carcinoma.

Hum Pathol 2021 Jan 28;107:9-19. Epub 2020 Sep 28.

Department of Pathology and Immunology, School of Medicine, Saint Louis, MO, 63110 USA. Electronic address:

The 5th edition of the World Health Organization (WHO) Classification of Tumours (Digestive System) recognizes a new subtype of colorectal adenocarcinoma, called adenoma-like adenocarcinoma. In this study, we sought to determine its clinicopathologic associations and how it is comparable with adenocarcinoma, of no special type (NOS). We retrospectively reviewed all available archival slides of stage I-III colonic adenocarcinoma resection specimens at our institution from 2013 to 2016.Ninety-one cases were classified as adenoma-like adenocarcinoma, and 251 cases were classified as adenocarcinoma, NOS. Of the adenoma-like adenocarcinoma cases, a majority (65 cases, 71%) were composed exclusively of adenoma-like features, designated as pure adenoma-like adenocarcinoma, whereas in the rest, the component of adenoma-like morphology was more than 50% but less than 100%, designated as mixed adenoma-like adenocarcinoma. Compared with adenocarcinoma, NOS, adenoma-like adenocarcinoma cases were significantly associated with the absence of tumor budding (P < 0.001), the absence of an immature/myxoid desmoplastic reaction (P < 0.001), the presence of intraepithelial tumor-infiltrating lymphocytes (P = 0.006), involvement of fewer lymph nodes ( P < 0.001), fewer tumor deposits (P = 0.042), lower pT stage (P = 0.047), lower pN stage (P < 0.001), and consequently the pTNM prognostic group (P < 0.001), as well as better recurrence-free survival (RFS), as per univariate analysis than adenocarcinoma, NOS cases (P = 0.026) but not as per multivariate analysis. However, mixed adenoma-like adenocarcinoma had a worse RFS than pure adenoma-like adenocarcinoma (hazard ratio = 1.639, 95% confidence interval = 0.494-5.437). Our findings not only support the importance of distinguishing this new subtype of colorectal adenocarcinoma but also raise the question whether mixed adenoma-like adenocarcinoma cases should be included in this category, and if so, whether 50% is an appropriate cutoff, as currently defined by the WHO.
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http://dx.doi.org/10.1016/j.humpath.2020.09.008DOI Listing
January 2021

Relative efficiency of equal versus unequal cluster sizes in cluster randomized trials with a small number of clusters.

J Biopharm Stat 2020 Sep 24:1-16. Epub 2020 Sep 24.

Division of Biostatistics, Washington University School of Medicine (WUSM) , St Louis, Missouri, 63110, USA.

To calculate sample sizes in cluster randomized trials (CRTs), the cluster sizes are usually assumed to be identical across all clusters for simplicity. However, equal cluster sizes are not guaranteed in practice, especially when the number of clusters is limited. Therefore, it is important to understand the relative efficiency (RE) of equal versus unequal cluster sizes when designing CRTs with a limited number of clusters. In this paper, we are interested in the RE of two bias-corrected sandwich estimators of the treatment effect in the Generalized Estimating Equation (GEE) models for CRTs with a small number of clusters. Specifically, we derive the RE of two bias-corrected sandwich estimators for binary, continuous, or count data in CRTs under the assumption of an exchangeable working correlation structure. We consider different scenarios of cluster size distributions and investigate RE performance through simulation studies. We conclude that the number of clusters could be increased by as much as 42% to compensate for efficiency loss due to unequal cluster sizes. Finally, we propose an algorithm of increasing the number of clusters when the coefficient of variation of cluster sizes is known and unknown.
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http://dx.doi.org/10.1080/10543406.2020.1814795DOI Listing
September 2020

Effect of Prophylactic Negative Pressure Wound Therapy vs Standard Wound Dressing on Surgical-Site Infection in Obese Women After Cesarean Delivery: A Randomized Clinical Trial.

JAMA 2020 09;324(12):1180-1189

Department of Obstetrics and Gynecology, University of Alabama at Birmingham.

Importance: Obesity increases the risk of both cesarean delivery and surgical-site infection. Despite widespread use, it is unclear whether prophylactic negative pressure wound therapy reduces surgical-site infection after cesarean delivery in obese women.

Objective: To evaluate whether prophylactic negative pressure wound therapy, initiated immediately after cesarean delivery, lowers the risk of surgical-site infections compared with standard wound dressing in obese women.

Design, Setting, And Participants: Multicenter randomized trial conducted from February 8, 2017, through November 13, 2019, at 4 academic and 2 community hospitals across the United States. Obese women undergoing planned or unplanned cesarean delivery were eligible. The study was terminated after 1624 of 2850 participants were recruited when a planned interim analysis showed increased adverse events in the negative pressure group and futility for the primary outcome. Final follow-up was December 18, 2019.

Interventions: Participants were randomly assigned to either undergo prophylactic negative pressure wound therapy, with application of the negative pressure device immediately after repair of the surgical incision (n = 816), or receive standard wound dressing (n = 808).

Main Outcomes And Measures: The primary outcome was superficial or deep surgical-site infection according to the Centers for Disease Control and Prevention definitions. Secondary outcomes included other wound complications, composite of surgical-site infections and other wound complications, and adverse skin reactions.

Results: Of the 1624 women randomized (mean age, 30.4 years, mean body mass index, 39.5), 1608 (99%) completed the study: 806 in the negative pressure group (median duration of negative pressure, 4 days) and 802 in the standard dressing group. Superficial or deep surgical-site infection was diagnosed in 29 participants (3.6%) in the negative pressure group and 27 (3.4%) in the standard dressing group (difference, 0.36%; 95% CI, -1.46% to 2.19%, P = .70). Of 30 prespecified secondary end points, 25 showed no significant differences, including other wound complications (2.6% vs 3.1%; difference, -0.53%; 95% CI, -1.93% to 0.88%; P = .46) and composite of surgical-site infections and other wound complications (6.5% vs 6.7%; difference, -0.27%; 95% CI, -2.71% to 2.25%; P = .83). Adverse skin reactions were significantly more frequent in the negative pressure group (7.0% vs 0.6%; difference, 6.95%; 95% CI, 1.86% to 12.03%; P < .001).

Conclusions And Relevance: Among obese women undergoing cesarean delivery, prophylactic negative pressure wound therapy, compared with standard wound dressing, did not significantly reduce the risk of surgical-site infection. These findings do not support routine use of prophylactic negative pressure wound therapy in obese women after cesarean delivery.

Trial Registration: ClinicalTrials.gov Identifier: NCT03009110.
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http://dx.doi.org/10.1001/jama.2020.13361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509615PMC
September 2020

Poly-dopamine, poly-levodopa, and poly-norepinephrine coatings: Comparison of physico-chemical and biological properties with focus on the application for blood-contacting devices.

Bioact Mater 2021 Jan 24;6(1):285-296. Epub 2020 Aug 24.

Key Lab of Advanced Technology of Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031, China.

Thanks to its simplicity, versatility, and secondary reactivity, dopamine self-polymerized coatings (pDA) have been widely used in surface modification of biomaterials, but the limitation in secondary molecular grafting and the high roughness restrain their application in some special scenarios. Therefore, some other catecholamine coatings analog to pDA have attracted more and more attention, including the smoother poly-norepinephrine coating (pNE), and the poly-levodopa coating (pLD) containing additional carboxyl groups. However, the lack of a systematic comparison of the properties, especially the biological properties of the above three catecholamine coatings, makes it difficult to give a guiding opinion on the application scenarios of different coatings. Herein, we systematically studied the physical, chemical, and biological properties of the three catecholamine coatings, and explored the feasibility of their application for the modification of biomaterials, especially cardiovascular materials. Among them, the pDA coating was the roughest, with the largest amount of amino and phenolic hydroxyl groups for molecule grafting, and induced the strongest platelet adhesion and activation. The pLD coating was the thinnest and most hydrophilic but triggered the strongest inflammatory response. The pNE coating was the smoothest, with the best hemocompatibility and histocompatibility, and with the strongest cell selectivity of promoting the proliferation of endothelial cells while inhibiting the proliferation of smooth muscle cells. To sum up, the pNE coating may be a better choice for the surface modification of cardiovascular materials, especially those for vascular stents and grafts, but it is still not widely recognized.
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http://dx.doi.org/10.1016/j.bioactmat.2020.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451900PMC
January 2021

Impact of a SBRT/SRS longitudinal telehealth training pilot course in Latin America.

Crit Rev Oncol Hematol 2020 Oct 7;154:103072. Epub 2020 Aug 7.

Rayos Contra Cancer, Inc. Nashville, TN, USA; University of California Irvine, Orange, CA, USA.

Purpose: To assess the impact of longitudinal telehealth training in stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) for clinicians in Latin America.

Materials And Methods: Professionals from two Peruvian centers received an initial SBRT/SRS on-site training course and subsequently received follow-up telehealth training (interventional group) or not (negative control arm). Twelve live video conference sessions were scheduled. Surveys pre- and post-curriculum measured participants' confidence in seven practical domains of SBRT/SRS, based on Likert scales of 1-5, and post-curriculum surveys assessed educators' experiences.

Results: Sixty-one participants were registered, with an average of 24 attendees per session. Pre- and post- surveys were completed by 22 participants. For interventional and negative-control groups, mean changes in Likert scale were satisfactory for the former and remained unmodified for the latter.

Conclusions: Conducting telehealth educational programs via virtual classroom sessions could be a reliable method to augment training for SBRT and SRS.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103072DOI Listing
October 2020

Adolescent dairy product and calcium intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study.

Cancer Causes Control 2020 Oct 2;31(10):891-904. Epub 2020 Aug 2.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.

Purpose: Although a growing body of evidence supports an early-life contribution to prostate cancer (PCa) development, few studies have investigated early-life diet, and only three have examined early-life dairy product intake, a promising candidate risk factor because of its known/suspected influence on insulin-like growth factor levels and height.

Methods: We used recalled dietary data from 162,816 participants in the NIH-AARP Diet and Health Study to investigate associations for milk, cheese, ice cream, total dairy, and calcium intake at ages 12-13 years with incident total (n = 17,729), advanced (n = 2,348), and fatal PCa (n = 827) over 14 years of follow-up. We calculated relative risks (RRs) and 95% confidence intervals (CIs) by Cox proportional hazards regression.

Results: We observed suggestive positive trends for milk, dairy, and calcium intake with total and/or advanced PCa (p-trends = 0.016-0.148). These trends attenuated after adjustment for additional components of adolescent diet, particularly red meat and vegetables/potatoes. In contrast, suggestive inverse trends were observed for cheese and ice cream intake with total and/or advanced PCa (p-trends = 0.043-0.153), and for milk, dairy, and calcium intake with fatal PCa (p-trend = 0.045-0.117).

Conclusion: Although these findings provide some support for a role of adolescent diet in increasing PCa risk, particularly for correlates of milk intake or overall dietary patterns, our protective findings for cheese and ice cream intake with PCa risk and mortality, and for all dairy products with PCa mortality, suggest alternative explanations, such as the influence of early-life socioeconomic status, and increased PCa screening, earlier detection, and better PCa care.
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http://dx.doi.org/10.1007/s10552-020-01330-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482419PMC
October 2020

A Patient Decision Support Tool for Hepatitis C Virus and CKD Treatment.

Kidney Med 2019 Jul-Aug;1(4):200-206. Epub 2019 Jul 11.

Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO.

Rationale & Objective: Patient education and decision support tools could facilitate decisions around the timing of antiviral therapy in patients living with both hepatitis C virus (HCV) infection and chronic kidney disease (CKD). We previously developed a tool through the HELP (Helping Empower Liver and Kidney Patients) study. This article evaluates the preliminary efficacy and usability of the tool among participants with both HCV infection and CKD.

Study Design: Pre-post study pilot evaluation.

Setting & Participants: Participants were at least 18 years old, were English speaking, and had a diagnosis of chronic HCV infection and CKD; they were seen in CKD clinics, dialysis units, and/or hepatology and liver transplantation clinics.

Intervention: Electronic patient decision support tool.

Outcomes: Participants' change in knowledge, certainty about choice, decision self-efficacy, patients' treatment preferences, and tool usability.

Results: 70 participants were recruited; 56 of 70 (80.0%) completed study procedures. Nearly all (51/56; 91.1%) requested paper-based study procedures despite the electronic design of the tool. Participants reported that they were most worried about the following treatment factors: (1) cost of drugs to treat HCV infection, (2) how their HCV infection affected their CKD, and (3) wait times for a kidney transplant. After using the decision tool, participants had significantly higher HCV infection and CKD knowledge (mean posttest percent of questions answered correctly = 65.74% vs pretest percent of questions answered correctly = 53.44%;  < 0.001) and more certainty about choice (mean posttest = 3.13 vs pretest = 2.65;   0.05). There were no significant changes in decision self-efficacy (mean posttest = 86.62 vs pretest = 84.68; 0.48).

Limitations: Single-site pilot study to explore preliminary tool efficacy and usability.

Conclusions: This study suggests that a decision tool may support informed patient-centered choices among patients with HCV infection and CKD. Future studies should evaluate ways to improve care decisions in a larger sample using both paper-based and electronic materials.

Funding: Merck & Co, Inc, Kenilworth, NJ.

Trial Registration: Registered at clinicaltrials.gov with study number NCT03426787.
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http://dx.doi.org/10.1016/j.xkme.2019.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380397PMC
July 2019

Sample size calculation in three-level cluster randomized trials using generalized estimating equation models.

Stat Med 2020 10 28;39(24):3347-3372. Epub 2020 Jul 28.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine (WUSM), St. Louis, Missouri, USA.

Three-level cluster randomized trials (CRTs) are increasingly used in implementation science, where 2fold-nested-correlated data arise. For example, interventions are randomly assigned to practices, and providers within the same practice who provide care to participants are trained with the assigned intervention. Teerenstra et al proposed a nested exchangeable correlation structure that accounts for two levels of clustering within the generalized estimating equations (GEE) approach. In this article, we utilize GEE models to test the treatment effect in a two-group comparison for continuous, binary, or count data in three-level CRTs. Given the nested exchangeable correlation structure, we derive the asymptotic variances of the estimator of the treatment effect for different types of outcomes. When the number of clusters is small, researchers have proposed bias-corrected sandwich estimators to improve performance in two-level CRTs. We extend the variances of two bias-corrected sandwich estimators to three-level CRTs. The equal provider and practice sizes were assumed to calculate number of practices for simplicity. However, they are not guaranteed in practice. Relative efficiency (RE) is defined as the ratio of variance of the estimator of the treatment effect for equal to unequal provider and practice sizes. The expressions of REs are obtained from both asymptotic variance estimation and bias-corrected sandwich estimators. Their performances are evaluated for different scenarios of provider and practice size distributions through simulation studies. Finally, a percentage increase in the number of practices is proposed due to efficiency loss from unequal provider and/or practice sizes.
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http://dx.doi.org/10.1002/sim.8670DOI Listing
October 2020

Shipping Lungs Greater Distances Increases Costs Without Cutting Waitlist Mortality.

Ann Thorac Surg 2020 11 6;110(5):1691-1697. Epub 2020 Jun 6.

Division of Cardiothoracic Surgery, Department of Surgery, Washington University, St Louis, Missouri. Electronic address:

Background: On November 24, 2017, a change in lung allocation policy was initiated to replace the donor service area with a 250-nautical-mile radius circle around the donor hospital. We aim to analyze the consequences of this change, including organ acquisition cost and transplant outcomes, at the national level.

Methods: Data on adult patients undergoing lung transplantation between April 27, 2017, and June 22, 2018 (30 weeks before to 30 weeks after allocation policy change) were extracted from the Scientific Registry of Transplant Recipients database. Patients were classified into pre-change and post-change subgroups. Six-month overall survival was evaluated by Kaplan-Meier analysis. Organ acquisition costs were compared between the pre-change and post-change groups.

Results: Of the 3317 adult patients removed from the waiting list during the study period (pre-change 1637 vs post-change 1680), 2734 underwent transplantation (pre-change 1371 of 1637 [83.8%] vs post-change 1363 of 1680 [81.1%]), and 382 died or became too sick to be transplanted (pre-change 168 of 1637 [10.3%] vs post-change 214 of 1680 [12.7%], P = .077). Six-month survival rates of transplanted patients were similar between the two groups. However, average organ acquisition costs increased after policy change (pre-change $50,735 ± $10,858 vs post-change $53,440 ± $10,247, P < .001) with an increase in nonlocal donors (pre-change 44.3% vs post-change 68.9%, P < .001).

Conclusions: Organ acquisition costs and resource utilization increased with the new lung allocation policy, whereas deaths on the waiting list or after transplantation did not decrease. Further optimization of the allocation policy is necessary to balance access to transplant and proper stewardship of human and financial resources.
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http://dx.doi.org/10.1016/j.athoracsur.2020.04.086DOI Listing
November 2020

Endpoint surrogacy in oncology Phase 3 randomised controlled trials.

Br J Cancer 2020 08 26;123(3):333-334. Epub 2020 May 26.

Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, Guangdong, China.

Endpoint surrogacy is an important concept in oncology trials. Using a surrogate endpoint like progression-free survival as the primary endpoint-instead of overall survival-would lead to a potential faster drug approval and therefore more cancer patients with an earlier opportunity to receive the newly approved drugs.
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http://dx.doi.org/10.1038/s41416-020-0896-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403397PMC
August 2020

Effect of metastatic site on survival in patients with neuroendocrine neoplasms (NENs). An analysis of SEER data from 2010 to 2014.

BMC Endocr Disord 2020 Apr 3;20(1):44. Epub 2020 Apr 3.

Department of Medicine, Washington University in St. Louis, St. Louis, USA.

Background: Neuroendocrine neoplasms (NENs) display variable behaviors based on origin and grade. We assumed that both tumor origin and the location of metastasis may play a role in survival.

Methods: We queried the SEER database (2010-2014) for patients with an established diagnosis of NENs and documented site of metastasis and identified 2005 patients. Overall survival (OS) at the time points were estimated by the Kaplan-Meier method Cox proportional-hazards models were used to evaluate the relationship of the interested variables and OS.

Results: Lung, liver, bone and brain metastases were observed in 9, 77, 7 and 6% of metastatic patients respectively. In the multivariate model, metastasis locations were significantly associated with worse survival (liver HR: 1.677 (1.226-2.294); (bone metastasis HR: 1.412 (0.965-2.065); brain HR: 1.666 (1.177-2.357)). We produced a scoring system based on site of origin, metastasis location, age, gender, histology and tumor size that can stratify metastatic NEN patients in low, intermediate and high-risk categories to help physicians with decision making.

Conclusion: Site of metastasis plays an important role in survival of metastatic NEN patients independent of commonly described prognostic factors and should be considered in survival estimates.
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http://dx.doi.org/10.1186/s12902-020-0525-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126407PMC
April 2020

Accuracy of Grading in Pancreatic Neuroendocrine Neoplasms and Effect on Survival Estimates: An Institutional Experience.

Ann Surg Oncol 2020 Sep 23;27(9):3542-3550. Epub 2020 Mar 23.

Department of Surgery, Washington University in St. Louis, St Louis, MO, USA.

Background: Accurate grading of neuroendocrine neoplasms (NENs) is crucial for proper assessment of prognosis. Estimation of the proliferative indices, if not performed properly, is largely erroneous due to significant intratumoral heterogeneity. We sought to establish the degree of error in the grading of a cohort of curatively resected pancreatic NENs (PanNENs) and the theoretical impact of that in a larger cohort of Surveillance, Epidemiology, and End Results (SEER) patients.

Methods: A retrospective query of an institutional surgical database was performed from 2000 to 2018 to identify optimally resected PanNENs, which were reviewed by two gastrointestinal pathologists and regraded according to the WHO 2017 classification. Overall survival and recurrence-free survival were estimated using the Kaplan-Meier method for original and new grading systems, respectively and Cox proportional hazards models were used to evaluate the effect of the interested variables, including new grading systems.

Results: A total of 176 cases were identified. After regrading, 17/64 (26.6%) G1 neoplasms were classified as G2 and 12/95 (12.6%) G2 neoplasms were classified as G1, while 1/11 (9.1%) G3 neoplasms were classified as G2. Our expert gastrointestinal pathologists agreed on 97% of reclassified cases by blind review. Application of the G1/G2 misclassification errors on various groups, including PanNENs, in a SEER database of 1385 patients rendered the reported survival differences nonsignificant (1000 repetitions; p = 0.063, 95% confidence interval 0.056-0.070).

Conclusions: Mischaracterization of grade is common in optimally resected PanNENs but is eliminated with proper training and adherence to guidelines. The discrepancy rates can cast doubt on the generally accepted survival differences between G1 and G2 patients, as surmised by large database analyses.
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http://dx.doi.org/10.1245/s10434-020-08377-xDOI Listing
September 2020

A stepped-wedge randomized trial protocol of a community intervention for increasing lung screening through engaging primary care providers (I-STEP).

Contemp Clin Trials 2020 04 14;91:105991. Epub 2020 Mar 14.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8100, St. Louis, MO 63110-0193, USA. Electronic address:

Lung cancer screening with low-dose computed tomography (LDCT) reduces lung cancer mortality, yet few eligible high-risk patients receive it annually. This protocol describes a community-partnered intervention (Toolkit) designed to support primary care practices in making referrals for lung screening and guiding patients into appropriate screening pathways. This study uses a stepped-wedge implementation design. Screening centers are randomized by readiness level to enter the intervention phase in three-month "steps" with pre-intervention data serving as the control. The primary outcome is whether delivery of the Toolkit to primary care practices results in a monthly increase in number of initial LDCT screenings. Six participating centers will identify 10 practices and reach 2-3 providers per practice to train them to use the Toolkit. The Toolkit will address known barriers to screening and referral at the patient and provider levels and provide support for required elements of screening. Toolkit components include adaptable evidence-based interventions to maximize compatibility with workflows. We hypothesize that after nine months of intervention delivery, the number of initial screening per center will double. Involving 60 practices achieves 80% power at 5% level of significance. Implementation outcomes such as adoption, acceptability, feasibility, adaptation, and sustainability will be assessed through field-notes and activity logs. LDCT for lung cancer screening currently reaches a small fraction of eligible adults. To reach the full potential to reduce mortality, primary care practices are an important venue for increasing appropriate referrals. This multidisciplinary trial will encourage acceptability and sustainability by using local knowledge and promoting partnership between providers and patients. Trial registration: ClinicalTrials.gov, NCT03958253.
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http://dx.doi.org/10.1016/j.cct.2020.105991DOI Listing
April 2020