The Test-retest Reliability of Pain Outcome Measures in People with Phantom Limb Pain.

OBJECTIVES: To quantify the test-retest reliability of three patient-reported outcome measures of pain for people living with phantom limb pain (PLP) and assess impact of test-retest errors on future research and clinical decisions. METHODS: Thirty-nine participants (30 males), mean (SD) age: 55 (16), mean (SD) years post amputation: 6.8 (8.3), reported their PLP levels on a Visual Analogue Scale (VAS) for pain intensity, the revised Short Form McGill Pain Questionnaire (SF-MPQ-2), and a pain diary, on two occasions 7-14 days apart. Mean systematic change, within-subjects SD, limits of agreement (LOA), coefficient of variation and the intraclass correlation coefficient (ICC) were quantified alongside their respective 95% confidence intervals (95%CI). RESULTS: Systematic learning effects (mean changes) were not clinically relevant across the VAS, SF-MPQ-2 and pain diary. Within-subjects SDs (95%CI) were 11.8 (9.6-15.3), 0.9 (0.7-1.2), and 8.6 (6.9-11.5), respectively. LOA (95%CI) were 32.6 (26.5-42.4), 2.5 (2-3.3), and 23.9 (19.2-31.8), respectively. ICCs (95%CI) were 0.8 (0.6-0.9), 0.8 (0.7-0.9), and 0.9 (0.8-0.9), respectively, but may have been inflated by sample heterogeneity. The test-retest errors allowed detection of clinically relevant effect sizes with feasible sample sizes in future studies, but individual errors were large. DISCUSSION: For people with PLP, a pain intensity VAS, the SF-MPQ-2, and a pain diary show an acceptable level of inter-session reliability for use in future clinical trials with feasible sample sizes. Nevertheless, the random error observed for all three of the pain outcome measures suggests they should be interpreted with caution in case studies and when monitoring individuals' clinical status and progress.

"When I was Younger, My Story Belonged to Everyone Else": Co-production of Resources for Adults Living with Craniosynostosis.

OBJECTIVE: Despite growing recognition that congenital craniofacial conditions have lifelong implications, psychological support for adults is currently lacking. The aim of this project was to produce a series of short films about living with craniosynostosis in adulthood, alongside a psychoeducational booklet. DESIGN: The resources were developed using multiple focus groups and meetings attended by researchers, patient representatives, a leading charitable organisation, an award-winning film production company, clinicians, and other experts in the field. RESULTS: An online mixed-methods survey was developed based on prior work to request feedback on the acceptability and utility of the resources from the craniosynostosis community. While data collection to evaluate the resources is ongoing, preliminary results (n = 36) highlight an acceptability rating of 100%. CONCLUSIONS: The resources developed represent a step forward in addressing the unmet information and support needs of adults with craniosynostosis and highlight the benefits of co-production in research.

Assessment of the bearing-down manoeuvre in pregnancy and detection of paradoxical levator ani muscle contraction using 2D transperineal ultrasound and vaginal palpation: a concurrent validity and inter-rater reliability study.

OBJECTIVE: To examine the concurrent validity and inter-rater reliability of vaginal palpation as a measure of the quality of the bearing-down manoeuvre (BDM) and the detection of a paradoxical levator ani muscle contraction (LAM) in pregnant women, compared with 2D transperineal ultrasound (TPUS). DESIGN: Concurrent validity and inter-rater reliability study. SETTING: Physiotherapy clinic. POPULATION: Twenty pregnant women in their third trimester. METHODS: The anterior posterior diameter (APD) was measured during the BDM using TPUS by one experienced physiotherapist. An APD that shortened by >2 mm from rest was described as LAM shortening, an APD that moved by 0-2 mm was described as no change and an APD that lengthened by >2 mm was described as LAM lengthening. Vaginal palpation described the LAM during the BDM as no movement, shortening or lengthening. Participants were allowed two attempts and the best attempt was measured. MAIN OUTCOME MEASURES: APD using TPUS and the assessor's subjective description of LAM during the BDM using vaginal palpation. RESULTS: TPUS detected more paradoxical LAM contractions during the BDM than palpation. Agreement between vaginal palpation and TPUS assessment for BDM was poor. The Fleiss kappa coefficients were 0.457 (90% CI 0.16-0.71) between TPUS and one assessor and 0.326 (90% CI 0.01-0.6) between TPUS and the other assessor. In addition, inter-rater reliability was poor between observers palpating the BDM, with a Fleiss kappa coefficient of 0.375 (90% CI 0.13-0.64). CONCLUSIONS: This study did not find vaginal palpation of the BDM in pregnant women to have concurrent validity or inter-rater reliability. Clinicians should be aware of potential inaccuracies when palpating the BDM, and, where possible, seek an assessment via TPUS.

Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer.

BACKGROUND: Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information. METHODS: We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years. RESULTS: Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1). CONCLUSIONS: Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).

Association of continuity of carer and women's experiences of maternity care during the COVID-19 pandemic: A cross-sectional survey.

BACKGROUND: Recent research highlights the impact of the COVID-19 pandemic on maternity services, although none to date have analysed the association between continuity of carer and how women felt about the changes to pregnancy care and birth plans. AIM: To describe pregnant women's self-reported changes to their planned pregnancy care and associations between continuity of carer and how women feel about changes to their planned care. METHODS: A cross-sectional online survey of pregnant women aged over 18 years in their final trimester of pregnancy in Australia. FINDINGS: 1668 women completed the survey. Most women reported at least one change to pregnancy care and birthing plans. Women receiving full continuity of carer were more likely to rate the changes to care as neutral/positive (p<.001) when compared with women who received partial or no continuity. DISCUSSION: Pregnant women experienced many changes to their planned pregnancy and birth care during the COVID-19 pandemic. Women who received full continuity of carer experienced fewer changes to care and were more likely to feel neutral/positive about the changes than women who did not receive full continuity of carer.

Australian University Nursing and Allied Health Students' and Staff Physical Activity Promotion Preparedness and Knowledge: A Pre-Post Study Using an Educational Intervention.

The promotion of physical activity (PA) by health professionals is a key strategy to increase PA levels in the population. In this study, we investigated PA promotion, preparedness, and knowledge among university nursing and allied health students and staff, as well as PA resource usage within curricula, before and after an educational intervention. Students and staff from 13 health disciplines at one Australian university were invited to complete an online survey, and a curriculum audits were conducted before and after PA teaching resources were promoted by academic PA champions (n = 14). A total of 299 students and 43 staff responded to the survey pre-intervention, and 363 and 32 responded to the post-intervention, respectively. PA promotion role perception (≥93%) and confidence to provide general PA advice (≥70%) were high throughout the study. Knowledge of PA guidelines was poor (3−10%). Students of physiotherapy, sport and exercise science, as well as more active students, were more likely to be aware of the PA guidelines (p < 0.05). Over 12 months, PA promotion preparedness and knowledge did not change significantly, nor was there a change in the amount of PA content delivered, despite a significant increase in the use of the teaching resources across a number of disciplines (p = 0.007). Future research should be carried out to investigate the implementation of the resources over time and to develop additional strategies for PA promotion and education scaffolded across curricula.

Identifying factors influencing study skills engagement and participation for online learners in higher education during COVID-19.

The COVID-19 pandemic disrupted education across the world as campuses closed to restrict the spread of the virus. UK universities swiftly migrated to online delivery. The experiences of students and staff during this transition can inform our return to campus and our ability to deal with future disruption. This study draws on Moore's theory of transactional distance to understand factors influencing student study skills engagement and participation in online learning during this period. We surveyed students (n = 178) in a computing school at a UK university. A partial least squares (PLS) analysis was used to explore the influence of transactional distance (between students/teachers and between students/students), access to e-learning capital, and perceived usefulness on two measures: study skills engagement and participation in online collaborative activity. Results show that transactional distance influences participation, and e-learning capital influences study skills engagement. Our findings suggest that if universities continue with aspects of online learning for previously on-campus students they should provide access to infrastructure and training on utilising the online ecosystem to avoid disadvantaging students. Further investment in students' e-learning capital, such as signposting and adapting existing resources, is also necessary to support this key influence in study skills engagement.

Incidental Finding of Gallbladder Torsion During Laparoscopic Cholecystectomy.

Laparoscopic cholecystectomy is a common general surgery procedure, with over a million laparoscopic cholecystectomies performed in the United States annually. A rare presentation, which may be encountered incidentally during surgery, is torsion of the gallbladder. Gallbladder torsion is encountered in 0.01% of all patients with acute cholecystitis. It should be considered in the differential diagnosis of elderly female patients presenting with symptoms of acute or chronic cholecystitis.  In this case report, we discuss the incidental finding of gallbladder torsion during laparoscopic cholecystectomy in an 82-year-old female admitted to the hospital with symptoms of cholecystitis. Preoperative CT imaging revealed a chronic, large hiatal hernia and a dilated gallbladder containing heterogeneous densities, possibly related to sludge. During the operation, a necrotic, torsed gallbladder and long cystic duct were found. A laparoscopic cholecystectomy was performed and the remainder of the patient's hospital course was uncomplicated. Intraoperatively, our patient was found to have torsion of the gallbladder. Preoperative lab values revealed mild hyponatremia, hypokalemia, and hypochloremia with normal liver enzymes, bilirubin, and alkaline phosphatase levels. This is consistent with documented cases, as typically the biliary tree is not obstructed. Additionally, preoperative imaging rarely reveals the diagnosis. Prompt detorsion and cholecystectomy should be performed to prevent gangrene and perforation. Gallbladder torsion can result in perforation if not quickly identified and treated. We recommend prompt laparoscopic detorsion and cholecystectomy to prevent perforation.

A systematic integrative review examining the impact of Australian rural and remote maternity unit closures.

BACKGROUND: Rural and remote Australian women are less able to access locally situated maternity care and birthing facilities, largely due to the gradual closures of rural and remote birthing services. Closures have occurred due to workforce issues, safety and quality issues and economic rationalisation of services to offset rising health system costs. An examination of the published literature to gain a deeper understanding of this phenomenon is warranted. QUESTION: What are the impacts of rural and remote maternity unit closures in Australia? METHODS: A systematic integrative review of published literature on Australian maternity unit closures was undertaken using Whittemore and Knafl's (2005) framework. A database search was conducted with date limiters of 2010 to 2020 on papers within the search parameters "maternity unit*" AND closure* AND women AND (midwife OR midwives) AND Australia, also with "birth unit", "labour ward" and "rural" in varying combinations. This search resulted in 348 papers. After applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) process and the Crowe Critical Appraisal Tool (CCAT) and discarding those non-relevant, seven papers remained. FINDINGS: A methodological analysis of seven papers occurred, three qualitative studies, three quantitative studies and one mixed methods study. Two main stakeholders were identified, the woman, and the health service. Women identified risks associated with travel, lack of access to services, costs or financial issues, safety, and emotional burdens. Women explicitly stated that access to local maternity services would negate many of their concerns. Health services indicated closures were due to safety and quality considerations and workforce issues. CONCLUSION: Conflict exists in trying to meet the perceived needs of both stakeholder groups. Published evidence supports midwifery models for low-risk women. National policy also supports woman-centred care; however, local service uptake is minimal due to organisational barriers.

Impact of induction strategy change on first-year rejection in pediatric heart transplantation at a single center-From postoperative basiliximab to either postoperative anti-thymocyte globulin or preoperative basiliximab.

BACKGROUND: Our pediatric heart transplant center transitioned from post-bypass basiliximab (BAS) induction to either anti-thymocyte globulin (ATG) or pre-bypass BAS. The purpose of this study was to compare first-year rejection rates before and after this change. METHODS: A single-center retrospective analysis was conducted of pediatric heart transplant recipients from 2010 to 2019. Primary outcome was first-year rejection. Bivariate analysis, Kaplan-Meier curves, and multivariable regression were performed across eras. RESULTS: Forty-three early era patients (55%) received post-bypass BAS, and 35 late era patients (45%) received pre-bypass BAS (n = 17) or ATG (n = 18). First-year rejection decreased in the late era (31% vs 53%, p = .05). This finding was more pronounced after excluding infants (38% vs 73%, p = .006). Late era was associated with a decreased likelihood of rejection (all cohort OR 0.19, 95% CI 0.05-0.66; infants excluded OR 0.17, 95% CI 0.04-0.61). No differences in post-transplant lymphoproliferative disease, donor-specific antibody, or infection were observed. CONCLUSIONS: Fewer late era patients receiving ATG or pre-bypass BAS induction had first-year rejection compared to the early era patients receiving standard post-bypass BAS induction. This programmatic shift in induction strategy was readily achievable and potentially effective in reducing first-year rejection.

DUCHESS: an evaluation of the ductal carcinoma in situ score for decisions on radiotherapy in patients with low/intermediate-risk DCIS.

BACKGROUND: Identification of women with DCIS who have a very low risk of local recurrence risk (LRR) after breast-conserving surgery (BCS) is needed to de-escalate therapy. We evaluated the impact of 10-year LRR estimates after BCS, calculated by the integration of a 12-gene molecular expression assay (Oncotype Breast DCIS Score®) and clinicopathological features (CPFs), on its ability to change radiation oncologists' recommendations for RT after BCS for DCIS. METHODS: Prospective cohort study of women with DCIS treated with BCS. Eligibility criteria were as follows: age > 45 years, tumor ≤ 2.5 cm, and margins ≥ 1 mm. Radiation oncologists provided 10-year LRR estimates without RT and recommendation for RT pre- and post-assay. Primary outcome was change in RT recommendation. RESULTS: 217 patients were evaluable, with mean age = 63 years, mean tumor size = 1.1 cm, and mean DCIS Score = 32; 140 (64%) were in the low-risk (<39), 32 (15%) were in the intermediate-risk (39-54), and 45 (21%) were in the high-risk groups (≥55). The assay led to a change in treatment recommendation in 76 (35.2%) (95%CI 29.1-41.8%) patients. RT recommendations decreased from 79% pre-assay to 50% post-assay (difference = 29%; 95%CI 22-35%) due to a significant increase in the proportion of patients with a predicted low LRR (< 10%) post-assay and recommendations to omit RT for those with a low predicted risk. The assay was associated with improved patient satisfaction and reduced decisional conflict. CONCLUSION: The DCIS Score assay combined with CPFs identified more women with an estimated low (<10%) 10-yr LR risk after BCS, leading to a significant decrease in recommendations for RT compared to estimates based on CPFs alone.

Cancer Burden Is Controlled by Mural Cell-ß3-Integrin Regulated Crosstalk with Tumor Cells.

Enhanced blood vessel (BV) formation is thought to drive tumor growth through elevated nutrient delivery. However, this observation has overlooked potential roles for mural cells in directly affecting tumor growth independent of BV function. Here we provide clinical data correlating high percentages of mural-ß3-integrin-negative tumor BVs with increased tumor sizes but no effect on BV numbers. Mural-ß3-integrin loss also enhances tumor growth in implanted and autochthonous mouse tumor models with no detectable effects on BV numbers or function. At a molecular level, mural-cell ß3-integrin loss enhances signaling via FAK-p-HGFR-p-Akt-p-p65, driving CXCL1, CCL2, and TIMP-1 production. In particular, mural-cell-derived CCL2 stimulates tumor cell MEK1-ERK1/2-ROCK2-dependent signaling and enhances tumor cell survival and tumor growth. Overall, our data indicate that mural cells can control tumor growth via paracrine signals regulated by ß3-integrin, providing a previously unrecognized mechanism of cancer growth control.

Child Development Outcomes of DIR/Floortime TM-based Programs: A Systematic Review.

BACKGROUND: Occupational therapy is often part of the multi-disciplinary approach within the Developmental, Individual-differences, Relationship-based (DIR) FloortimeTM Model. The model addresses the emotional development of children, which is considered to be critical for the other child developmental areas. PURPOSE: This review serves to inform practitioner decision-making about the use of this model, as no systematic reviews exist on child development outcomes. METHODS: The systematic search included Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Cochrane. For critical appraisal, the McMaster Critical Review was utilized. FINDINGS: Nine studies were identified with varying quality levels. Outcomes were mostly reported for increased socio-emotional development. IMPLICATIONS: The evidence base for this model is emerging from a published research perspective. It is recommended that the use of this model be supported by sound clinical reasoning processes, intervention fidelity, use of valid outcome measures, and regular monitoring. Higher quality research is urgently needed to progress the research base for this intervention.

Comparing deep learning-based auto-segmentation of organs at risk and clinical target volumes to expert inter-observer variability in radiotherapy planning.

BACKGROUND: Deep learning-based auto-segmented contours (DC) aim to alleviate labour intensive contouring of organs at risk (OAR) and clinical target volumes (CTV). Most previous DC validation studies have a limited number of expert observers for comparison and/or use a validation dataset related to the training dataset. We determine if DC models are comparable to Radiation Oncologist (RO) inter-observer variability on an independent dataset. METHODS: Expert contours (EC) were created by multiple ROs for central nervous system (CNS), head and neck (H&N), and prostate radiotherapy (RT) OARs and CTVs. DCs were generated using deep learning-based auto-segmentation software trained by a single RO on publicly available data. Contours were compared using Dice Similarity Coefficient (DSC) and 95% Hausdorff distance (HD). RESULTS: Sixty planning CT scans had 2-4 ECs, for a total of 60 CNS, 53 H&N, and 50 prostate RT contour sets. The mean DC and EC contouring times were 0.4 vs 7.7 min for CNS, 0.6 vs 26.6 min for H&N, and 0.4 vs 21.3 min for prostate RT contours. There were minimal differences in DSC and 95% HD involving DCs for OAR comparisons, but more noticeable differences for CTV comparisons. CONCLUSIONS: The accuracy of DCs trained by a single RO is comparable to expert inter-observer variability for the RT planning contours in this study. Use of deep learning-based auto-segmentation in clinical practice will likely lead to significant benefits to RT planning workflow and resources.

Resource allocation to growth or luxury consumption drives mycorrhizal responses.

Highly variable phenotypic responses in mycorrhizal plants challenge our functional understanding of plant-fungal mutualisms. Using non-invasive high-throughput phenotyping, we observed that arbuscular mycorrhizal (AM) fungi relieved phosphorus (P) limitation and enhanced growth of Brachypodium distachyon under P-limited conditions, while photosynthetic limitation under low nitrogen (N) was exacerbated by the fungus. However, these responses were strongly dependent on host genotype: only the faster growing genotype (Bd3-1) utilised P transferred from the fungus to achieve improved growth under P-limited conditions. Under low N, the slower growing genotype (Bd21) had a carbon and N surplus that was linked to a less negative growth response compared with the faster growing genotype. These responses were linked to the regulation of N : P stoichiometry, couples resource allocation to growth or luxury consumption in diverse plant lineages. Our results attest strongly to a mechanism in plants by which plant genotype-specific resource economics drive phenotypic outcomes during AM symbioses.

Prospective Assessment of Ultrasound Shear Wave Elastography for Discriminating Biliary Atresia from other Causes of Neonatal Cholestasis.

OBJECTIVE: To prospectively assess the diagnostic performance of ultrasound shear wave elastography (SWE) and hepatobiliary laboratory biomarkers for discriminating biliary atresia from other causes of neonatal cholestasis. STUDY DESIGN: Forty-one patients <3 months of age with neonatal cholestasis (direct bilirubin >2 mg/dL) and possible biliary atresia were prospectively enrolled. Both 2-dimensional (2D) and point ultrasound SWE were performed prior to knowing the final diagnosis. Median 2D (8) and point (10) shear wave speed measurements were calculated for each subject and used for analyses. The Mann-Whitney U test was used to compare shear wave speed and laboratory measurements between patients with and without biliary atresia. Receiver operating characteristic curve analyses and multivariable logistic regression were used to evaluate diagnostic performance. RESULTS: Thirteen subjects (31.7%) were diagnosed with biliary atresia, and 28 subjects (68.3%) were diagnosed with other causes of neonatal cholestasis. Median age at the time of ultrasound SWE was 37 days. Median 2D (2.08 vs 1.49 m/s, P = .0001) and point (1.95 vs 1.21 m/s, P = .0014) ultrasound SWE measurements were significantly different between subjects with and without biliary atresia. Using a cut-off value of >1.84 m/s, 2D ultrasound SWE had a sensitivity = 92.3%, specificity = 78.6%, and area under the receiver operating characteristic curve (AuROC) of 0.89 (P < .0001). Using a cut-off value of >320 (U/L), gamma-glutamyl transferase (GGT) had a sensitivity = 100.0%, specificity = 77.8%, and AuROC of 0.85 (P < .0001). Multivariable logistic regression demonstrated an AuROC of 0.93 (P < .0001), with 2 significant covariates (2D ultrasound SWE [OR = 23.06, P = .01]; GGT [OR = 1.003, P = .036]). CONCLUSIONS: Ultrasound SWE and GGT can help discriminate biliary atresia from other causes of neonatal cholestasis.

Ultrasound Elastography as a Non-Invasive Method to Monitor Liver Disease in Children with Short Bowel Syndrome: Updated Results.

PURPOSE: The purpose of the study was to determine the accuracy of acoustic radiation force impulse (ARFI) ultrasound elastography in assessing the degree of liver disease in children with short bowel syndrome (SBS). METHODS: A prospective observational cohort study of patients with SBS who underwent a liver biopsy and ARFI elastography was performed. Mean shear wave speed (SWS) and stage of fibrosis was evaluated using t-tests. Receiver operating characteristic curves (ROC) were generated and the area under the curves (AUC) estimated in order to assess the accuracy of SWS measurements to discriminate between stages of fibrosis. RESULTS: Thirty-seven paired elastography and biopsy samples from 31 patients were included. The median age was 0.6 years, and 61% were male. There was a significant positive correlation between stage of fibrosis and mean SWS (ß=0.16 m/s increase per stage, p=<0.001). ROC analysis revealed that mean SWS had good accuracy for discriminating between mild liver fibrosis (F0-F1) and moderate to severe fibrosis (F2-F4) (AUC=0.80, 95% CI 0.65-0.95). In addition, ROC analysis demonstrated that mean SWS can also accurately discriminate between mild to moderate fibrosis (F0-F2) and more severe fibrosis (F3-F4) (AUC=0.84, 95% CI 0.71-0.96). CONCLUSION: ARFI elastography is an accurate, non-invasive method to monitor liver disease in children with SBS. TYPE OF STUDY: Retrospective Cohort Study LEVEL OF EVIDENCE: II.

Real-time interactive planning for radiotherapy of head and neck cancer with volumetric modulated arc therapy.

BACKGROUND AND PURPOSE: Planning complex radiotherapy treatments can be inefficient, with large variation in plan quality. In this study we evaluated plan quality and planning efficiency using real-time interactive planning (RTIP) for head and neck (HN) volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: RTIP allows manipulation of dose volume histograms (DVHs) in real-time to assess achievable planning target volume (PTV) coverage and organ at risk (OAR) sparing. For 20 HN patients previously treated with VMAT, RTIP was used to minimize OAR dose while maintaining PTV coverage. RTIP DVHs were used to guide VMAT optimization. Dosimetric differences between RTIP-assisted plans and original clinical plans were assessed. Five blinded radiation oncologists indicated their preference for each PTV, OAR and overall plan. To assess efficiency, ten patients were planned de novo by experienced and novice planners and a RTIP user. RESULTS: The average planning time with RTIP was <20 min, and most plans required only one optimization. All 20 RTIP plans were preferred by a majority of oncologists due to improvements in OAR sparing. The average maximum dose to the spinal cord was reduced by 10.5 Gy (from 49.5 to 39.0 Gy), and the average mean doses for the oral cavity, laryngopharynx, contralateral parotid and submandibular glands were reduced by 3.5 Gy (39.1-35.7 Gy), 6.8 Gy (42.5-35.7 Gy), 1.7 Gy (17.0-15.3 Gy) and 3.3 Gy (22.9-19.5 Gy), respectively. CONCLUSIONS: Incorporating RTIP into clinical workflows may increase both planning efficiency and OAR sparing.

Pediatric Fontan Associated Liver Disease: Non-invasive Evaluation with Serologic Markers and Acoustic Radiation Force Impulse (ARFI) Elastography.

Hepatic fibrosis is a significant complication in adult Fontan patients suggesting development as a function of time since the surgery. Children with Fontan circulation are not routinely assessed for development of liver disease. We aimed to evaluate the effectiveness of serologic biomarkers and acoustic radiation force impulse (ARFI) elastography to detect liver disease in pediatric Fontan patients. Patients ≥ 1 year after Fontan operation prospectively had hepatic US with acoustic radiation force impulse and laboratory testing. Clinical cardiac data (echocardiograms, cardiac catheterizations) were reviewed. Statistical analysis was performed using Pearson's correlation coefficient, Wilcoxon rank-sum test and Kruskal-Wallis test. Forty patients were enrolled with median age of 11 years and median time since Fontan of 6.5 years. Platelet count negatively correlated with years since Fontan (p < 0.000). Thrombocytopenia was noted in 15% of patients with the lowest platelet count of 78 K/cu mm, in a patient >10 years from the Fontan (DORV) operation. Alanine transaminase (ALT, p = 0.034) and aspartate aminotransferase (AST, p = 0.009) were higher in patients with Extracardiac Conduit Fontan and not in other Fontan operations. Heterogeneous echotexture on liver ultrasound correlated with years since Fontan (p = 0.022), however all acoustic radiation force impulse values were elevated (> 1.34 m/s) and did not correlate with age, years since Fontan, labs or imaging. FibroSure values did not correlate with years since Fontan. This suggests that ARFI may be elevated due to passive hepatic congestion, limiting its value in this patient population. Additional testing is necessary to identify reliable noninvasive screening modalities for hepatic fibrosis in Fontan patients. Our study is the largest pediatric study to evaluate ARFI in patients after the Fontan operation and showed increased shear wave speed for all patients with no correlation with time since palliation. Decreasing platelet count may indicate the development of liver fibrosis.