Function Of Patient Age Research Articles

The Relationship Between Age and 30-Day Outcomes Following Unicompartmental Versus Total Knee Arthroplasty

BackgroundAn enhanced understanding of the short-term complication profile following unicompartmental knee arthroplasty (UKA) versus total knee arthroplasty (TKA) can improve surgical decision-making and subsequent patient outcomes. This study aimed to determine if the difference in risk of 30-day morbidity and mortality between UKA and TKA varied as a function of patient age. MethodsThis retrospective study of a national quality improvement database using data from 2014 to 2020 included 403,342 patients undergoing UKA (n = 12,324) or TKA (n = 391,018). A generalized additive model (GAM) evaluated non-linear relationships between primary outcome and predictors (age, procedure type, and procedure type x age interaction) using a 1:5 UKA to TKA matched sample. Probabilities and odds ratios (95% CI [confidence interval]) estimated the relative risk of complications across the age spectrum. ResultsIn the GAM, TKA patients relative to UKA had 1.30 higher odds (95% CI 1.19 to 1.43, P < 0.001) of 30-day morbidity and mortality. There was a significant, non-linear relationship between age and the primary outcome (P = 0.02), such that the odds were lowest at younger ages. They increased slowly until about age 65 years, at which point the slope became steeper. The interaction terms for age and procedure type were not significant (P = 0.30). The 30-day probability for short-term complications of a 65-, 75-, and 85-year-old undergoing UKA was 2.1% (95% CI, 1.8 to 2.3), 2.4% (95% CI, 2.0 to 2.8), and 3.2% (95% CI, 2.3 to 4.1), respectively. Conversely, the probability of a 65-, 75-, and 85-year-old undergoing TKA was 2.9% (95% CI, 2.7 to 3.0), 3.6% (95% CI, 3.3 to 3.8), and 5.5% (95% CI, 4.7 to 6.3). ConclusionsPatients undergoing UKA had a quantifiable lower likelihood of morbidity or mortality than TKA at all ages. These data can provide individualized risk for UKA and TKA across the age spectrum and could be helpful in counseling patients regarding their risk for perioperative complications.

Microfragmented abdominal adipose tissue-derived stem cells from knee osteoarthritis patients aged 29-65 years demonstrate in vitro stemness and low levels of cellular senescence.

To investigate the level of cellular senescence in stem cells derived from microfragmented abdominal adipose tissue harvested from patients with knee osteoarthritis (OA). Stem cells harvested from microfragmented abdominal adipose tissue from 20 patients with knee OA, aged 29-65 years (mean = 49.8, SD = 9.58), were analysed as a function of patient age and compared with control cells exhibiting signs of cellular senescence. Steady-state mRNA levels of a panel of genes associated with senescence were measured by qPCR. Intracellular senescence-associated proteins p16 and p21, and senescence-associated β-galactosidase activity were measured by flow cytometry. Cellular proliferation was assessed using a 5-ethynyl-2'-deoxyuridine proliferation assay. Stemness was assessed by stem cell surface markers using flow cytometry and the capacity to undergo adipogenic and osteogenic differentiation in vitro. No correlation was found between cellular senescence levels of the microfragmented adipose tissue-derived stem cells and patient age for any of the standard assays used to quantify senescence. The level of cellular senescence was generally low across all senescence-associated assays compared to the positive senescence control. Stemness was verified for all samples. An increased capacity to undergo adipogenic differentiation was shown with increasing patient age (p = 0.02). No effect of patient age was found for osteogenic differentiation. Autologous microfragmented adipose tissue-derived stem cells may be used in clinical trials of knee OA of patients aged 29-65 years, at least until passage 4, as they show stemness potential and negligible senescence in vitro. Not applicable.

Structural and functional connectivity in hydrocephalus: a scoping review.

Optimizing the treatment of hydrocephalus remains a major challenge in adult and pediatric neurosurgery. Currently, clinical treatment relies heavily on anatomic imaging of ventricular size and clinical presentation. The emergence of functional and structural brain connectivity imaging has provided the basis for a new paradigm in the management of hydrocephalus. Here we review the pertinent advances in this field. Following PRISMA-ScR guidelines for scoping reviews, we searched PubMed for relevant literature from 1994 to April 2023 using hydrocephalus and MRI-related terms. Included articles reported original MRI data on human subjects with hydrocephalus, while excluding non-English or pre-1994 publications that didn't match the study framework. The review identified 44 studies that investigated functional and/or structural connectivity using various MRI techniques across different hydrocephalus populations. While there is significant heterogeneity in imaging technology and connectivity analysis, there is broad consensus in the literature that 1) hydrocephalus is associated with disruption of functional and structural connectivity, 2) this disruption in cerebral connectivity can be further associated with neurologic compromise 3) timely treatment of hydrocephalus restores both cerebral connectivity and neurologic compromise. The robustness and consistency of these findings vary as a function of patient age, hydrocephalus etiology, and the connectivity region of interest studied. Functional and structural brain connectivity imaging shows potential as an imaging biomarker that may facilitate optimization of hydrocephalus treatment. Future research should focus on standardizing regions of interest as well as identifying connectivity analysis most pertinent to clinical outcome.

The network structure of the corneal endothelium.

A generic network model is applied to study the structure of the mammalian corneal endothelium. The model has been shown to reproduce the network properties of a wide range of systems, from low-dimensional inorganic glasses to colloidal nanoparticles deposited on a surface. Available extensive experimental microscopy results are analyzed and combined to highlight the behavior of two key metrics, the fraction of hexagonal rings (p6) and the coefficient of variation of the area. Their behavior is analyzed as a function of patient age, the onset of diabetes, and contact lens wearing status. Wearing contact lenses for ∼10 years is shown to change the endothelium structure by the equivalent of ∼30 years contact lens-free. Model network configurations are obtained using a Monte Carlo bond-switching algorithm, with the resulting topologies controlled by two potential model parameters (the bond and angular force constants) and the Monte Carlo temperature. The effect of systematically varying these parameters is investigated. In addition, the effect of constraining the ring size distribution is investigated. The networks generated with relatively weak bond force constants are shown to correlate best with the experimental information. The importance of extracting the full ring size distribution (rather than simply the fraction of hexagons) is discussed.

Artificial Intelligence Outperforms Kaplan–Meier Analyses Estimating Survival after Elective Treatment of Abdominal Aortic Aneurysms

Long term differences in survival after elective repair of abdominal aortic aneurysms (AAAs) between open surgical repair (OSR) and endovascular aneurysm repair (EVAR) are unclear, and hitherto artificial intelligence has not been used for this purpose. The aim was to compare the precision of survival estimates between the Kaplan-Meier (KM) method and the artificial intelligence derived method Neural Multi-Task Logistic Regression (N-MTLR), and to compare survival estimates as a function of patient age and time since surgery between OSR and EVAR using N-MTLR. All AAAs in Denmark were identified in the Danish vascular registry between 2003 and 2018. Survival was estimated using the KM and N-MTLR methods, and prediction performance was estimated with the Brier score. 7 912 patients were included in the study, n = 6 569 (83%) men, median age 72 years (range 35 - 92), with a median follow up time of 45.7 months (range 0 - 120). The two treatment cohorts, OSR n = 5 495 (69%), and EVAR n = 2 417 (31%), differed significantly in patient characteristics. The Brier score for KM increased from 0.044 to 0.244, and for N-MTLR from 0.044 to 0.206, from 90 days to 10 years. The N-MTLR method was more accurate than KM from 90 days to 10 years after surgery, p ≤ .025. N-MTLR demonstrated significant increased probability for survival for OSR in patients aged 58 - 76 years at five years, and 65 - 73 at 10 years after surgery, and the opposite was found for the benefit of EVAR in patients aged 72 - 85 years at one year, 85 - 90 years at five years, and for 85 - 90 year olds at 10 years after surgery. N-MTLR outperforms KM for the entire post-operative follow up time. This N-MTLR model has the potential to render more precise patient specific survival estimates, and establish survival differences between subgroups of patients that KM is unable to detect, demonstrated here for different age groups.

Looking Through the Crystal Ball of Data Science

Artificial Intelligence Outperforms Kaplan–Meier Analyses Estimating Survival after Elective Treatment of Abdominal Aortic AneurysmsEuropean Journal of Vascular and Endovascular SurgeryPreviewLong term differences in survival after elective repair of abdominal aortic aneurysms (AAAs) between open surgical repair (OSR) and endovascular aneurysm repair (EVAR) are unclear, and hitherto artificial intelligence has not been used for this purpose. The aim was to compare the precision of survival estimates between the Kaplan–Meier (KM) method and the artificial intelligence derived method Neural Multi-Task Logistic Regression (N-MTLR), and to compare survival estimates as a function of patient age and time since surgery between OSR and EVAR using N-MTLR. Full-Text PDF Open Access

EPID-15. SURGICAL RESECTION OF BENIGN MENINGIOMAS IN THE ELDERLY POPULATION: IMPLICATIONS FROM A PROPENSITY-SCORE MATCHED ANALYSIS

Abstract Object We characterized the patterns of clinical practice in benign meningioma resection and survival outcome as a function of patient age using the Surveillance, Epidemiology and End Results (SEER) and the SEER-Medicare database. METHODS The likelihood for recommendation to proceed with resection and survival in adult, benign meningioma patients were characterized using logistic regression. Survival analysis was performed using a propensity-score matching (PSM)-method (covariates balanced in PSM: socio-demographics, facility features, and comorbidities) through a multivariable logistic regression and accelerated failure time (AFT) models. RESULTS The likelihoods of recommendation for surgery were 0.59 (95%CI = 0.53-0.66, P &amp;lt; 0.001) and 0.17 (95%CI = 0.15-0.21, P &amp;lt; 0.001) for meningioma patients age 60-79 and ≥ 80, relative to patients age 40-59. Expectedly, the hazard of death increased with advancing aging strata in patients who underwent meningioma resection. To account for mortality risk associated with normal aging, a PSM analysis was performed to calculate the hazard of death for surgically resected meningioma patients relative to an age- and PSM-matched cancer-free patient cohort. This odds ratio (OR) was 3.84 (95%CI: 3.15-4.67, P &amp;lt; 0.001) for patients age 60-79 and 3.41 (95%CI: 2.56-4.56, P &amp;lt; 0.001) for patients age ≥ 80. These two ORs were not statistically different (ROR: 0.89, 95%CI: 0.63-1.62, P = 0.512), suggesting that the likelihood of death after benign meningioma resection was not significantly elevated in patients age ≥ 80 after accounting for expected age-related mortality. CONCLUSION Our study suggests that surgeons exert caution in selecting elderly with meningioma for resection. After accounting for mortality risk associated with normal aging and patient selection by the surgeon, the likelihood of death for patients age ≥ 80 who underwent meningioma resection was comparable to that observed for patients age 60-79.

Gastric DLBCL clonal evolution as function of patient age.

Diffuse large B cell lymphoma (DLBCL) is the most common type of NHL, accounting for about 40% of NHL cases, and is one of the most aggressive lymphomas. DLBCL is widespread in individuals aged more than 50 years old, with a maximum incidence in the seventh decade, but it may also occur in younger patients. DLBCL may occur in any immune system tissue, including those around the gastrointestinal tract, and even in the stomach, though gastric DLBCL has yet to be sufficiently investigated. This study aimed to understand changes in gastric Diffuse Large B cell lymphoma (gastric DLBCL) development with age. Immunoglobulin (Ig) heavy chain variable region genes were amplified from sections of nine preserved biopsies, from patients whose age varied between 25 and 89 years, sequenced and analyzed. We show first that identification of the malignant clone based on the biopsies is much less certain than was previously assumed; and second that, contrary to expectations, the repertoire of gastric B cell clones is more diverse among the elderly DLBCL patients than among the young.

Evaluation of the role of KPNA2 mutations in breast cancer prognosis using bioinformatics datasets

Breast cancer, comprising of several sub-phenotypes, is a leading cause of female cancer-related mortality in the UK and accounts for 15% of all cancer cases. Chemoresistant sub phenotypes of breast cancer remain a particular challenge. However, the rapidly-growing availability of clinical datasets, presents the scope to underpin a data-driven precision medicine-based approach exploring new targets for diagnostic and therapeutic interventions.We report the application of a bioinformatics-based approach probing the expression and prognostic role of Karyopherin-2 alpha (KPNA2) in breast cancer prognosis. Aberrant KPNA2 overexpression is directly correlated with aggressive tumour phenotypes and poor patient survival outcomes. We examined the existing clinical data available on a range of commonly occurring mutations of KPNA2 and their correlation with patient survival.Our analysis of clinical gene expression datasets show that KPNA2 is frequently amplified in breast cancer, with differences in expression levels observed as a function of patient age and clinicopathologic parameters. We also found that aberrant KPNA2 overexpression is directly correlated with poor patient prognosis, warranting further investigation of KPNA2 as an actionable target for patient stratification or the design of novel chemotherapy agents.In the era of big data, the wealth of datasets available in the public domain can be used to underpin proof of concept studies evaluating the biomolecular pathways implicated in chemotherapy resistance in breast cancer.

Study of Patients’ Return to Surgery Post-Tonsillectomy and/or Adenoidectomy: A Relation Between Patient Age and Timing of Uncontrolled Bleeding

Background: Tonsillectomy and/or adenoidectomy (T/A) are common surgical procedures. Postoperative uncontrolled bleeding is a well-established complication; however, the relation between certain variables and uncontrolled bleeding are unclear. Methods: We explored the Pennsylvania Patient Safety Reporting System database for event reports that described a patient who had a T/A procedure and later returned to surgery to control bleeding. We analyzed the post-T/A bleeding events according to numerous variables, such as patient sex and age, timing of the bleed, procedure performed (i.e., tonsillectomy and/or adenoidectomy), and bleeding site. Results: We identified 219 event reports from 56 healthcare facilities over a four-year period. The study revealed that 78% of the patients were discharged and then returned to surgery to control bleeding. Patients ranged in age from 1–45 years and 53% were female. Among the 219 events, 41% were a primary bleed (0–1 postoperative days) and 59% were a secondary bleed (2–30 postoperative day). Additionally, 0–1 days and 6–7 days after operation were the periods when patients most frequently returned to surgery (range of 0–30 days). We expanded upon much of the previous research by exploring the relation between patient age and days postoperative return to surgery. We found that a majority of patients in age categories 1–10, 11–20, and 21–30 years had a secondary bleed; in contrast, a majority of patients age 31–45 had a primary bleed. Conclusion: Our findings indicate that the post-T/A timing of uncontrolled bleeding may vary systematically as a function of patient age; however, future research is needed to better understand this topic. We encourage readers to use our findings, along with findings from previous research, to inform their practice and strategies to mitigate risk of patient harm.

Is Mini Percutaneous Nephrolithotomy a Game Changer for the Treatment of Renal Stones in Children?

BackgroundMini percutaneous nephrolithotomy (MPCNL) is a newer surgical procedure that has changed the management of paediatric renal stones. ObjectiveTo evaluate MPCNL morbidity and success rates for renal stones as a function of patient age in a paediatric cohort. Design, setting, and participantsThis was a retrospective case series that included 143 consecutive patients younger than 17 yr who underwent MPCNL at our institution between January 2016 and November 2020. The patients were categorised into three different age groups: <6 yr (n = 71, 49.7%), 6–11 yr (n = 44, 30.8%), and 12–17 yr (n = 28, 19.6%). MPCNL was performed in all patients through 16–20Fr tracts. Outcome measurements and statistical analysisThe stone-free rate, perioperative complications, tract number, operative time, postoperative haemoglobin change, and hospitalisation time were evaluated for each age group. Results and limitationsMPCNL was performed in 143 paediatric patients (88 boys and 55 girls; mean age 6.53 yr). The mean stone burden (± standard deviation) was 2.096 ± 1.01 cm in group one, 2.05 ± 1.05 cm in group two, and 3.46 ± 19.94 cm in group three; group three was significantly larger (p = 0.001). After a single MPCNL session, 92.42% of patients experienced complete stone clearance. All age groups were similar in terms of stone-free rate (p = 0.82), hospitalisation time (p = 0.94), postoperative haemoglobin change (p = 0.06), and perioperative complications (p = 0.62). However, stone size (p = 0.009), stone complexity (p = 0.001), number of access points (p = 0.03), and operative time (p = 0.009) were higher in the group aged 12–17 yr. ConclusionsMPCNL is an effective and safe procedure in younger as well as older children. Age should not be considered a limiting factor for MPCNL in children, and MPCNL should be considered the primary option for treating paediatric renal stones when PCNL is indicated. Patient summaryOur results show that surgical removal of kidney stones through an incision in the skin and using miniaturised instruments is an effective and safe procedure for children.

SURG-14. COMPARABLE SURVIVAL OUTCOMES BETWEEN THE ELDERLY AND THEIR YOUNGER COUNTERPARTS AFTER RESECTION OF BENIGN MENINGIOMAS

Abstract OBJECTIVE Using the Surveillance, Epidemiology and End Results (SEER) database, we characterized the patterns of surgical recommendations and outcomes after benign meningioma resection in the elderly population. METHODS 27,839 adult meningioma patients were identified in SEER between 1973- 2015 and 6,967 patients were identified between 2016-18. Patients were stratified into four age groups:18-39, 40-59, 60-79, and &amp;gt; 80 years old. The likelihood for recommendation to proceed with resection, extent of resection, and survival outcome were determined using logistic regression models. RESULTS In a multi-variate model that accounted for gender, race, marital status, tumor size, and tumor location, the likelihood of recommendation to proceed with benign meningiomas resection decreased with advancing age. Relative to patients age 40-59, the likelihood of recommendation for surgery were 1.130 (95%CI=0.925-1.380, P=0.230), 0.593 (95%CI=0.531-0.662, P&amp;lt; 0.001), and 0.173 (95%CI=0.146-0.205, P&amp;lt; 0.001) for patients age 18-39, 60-79, and &amp;gt;= 80, respectively. A similar trend in the likelihood of gross total resection (GTR) was observed. Relative to patients age 40-59, the likelihood of gross total resection were 1.009 (95%CI=0.913-1.114, P=0.867), 0.903 (95%CI=0.849-0.961, P=0.001), and 0.580 (95%CI=0.512-0.657, P&amp;lt; 0.001) for patients age 18-39, 60-79, and &amp;gt;= 80, respectively. However, survival after meningioma resection did not vary significantly as a function of patient age. Relative to patients age 40-59, the hazard of death after GTR of meningioma resection were 1.324 (95%CI=0.795-2/203, P=0.280), 0.813 (95%CI=0.639-1.035, P=0.092), and 0.913 (95%CI=0.618-1.350, P=0.649) for patients age 60-79, and &amp;gt;= 80, respectively. These results were validated using SEER data from 2016-2018. CONCLUSION This analysis provide evidence that surgeons exert caution in surgical resection of benign meningioma in the elderly, with decreased likelihood for recommending surgery in this population. In patients selected for and underwent gross resection, survival outcome in the elderly was comparable to their younger counterparts, suggesting safety of procedure in appropriately selected elderly.

U.S. Diagnostic Reference Levels and Achievable Doses for 10 Pediatric CT Examinations.

Background Diagnostic reference levels (DRLs) and achievable doses (ADs) were developed for the 10 most commonly performed pediatric CT examinations in the United States using the American College of Radiology Dose Index Registry. Purpose To develop robust, current, national DRLs and ADs for the 10 most commonly performed pediatric CT examinations as a function of patient age and size. Materials and Methods Data on 10 pediatric (ie, patients aged 18 years and younger) CT examinations performed between 2016 and 2020 at 1625 facilities were analyzed. For head and neck examinations, dose indexes were analyzed based on patient age; for body examinations, dose indexes were analyzed for patient age and effective diameter. Data from 1 543 535 examinations provided medians for AD and 75th percentiles for DRLs for volume CT dose index (CTDIvol), dose-length product (DLP), and size-specific dose estimate (SSDE). Results Of all facilities analyzed, 66% of the facilities (1068 of 1625) were community hospitals, 16% (264 of 1625) were freestanding centers, 9.5% (154 of 1625) were academic facilities, and 3.5% (57 of 1625) were dedicated children's hospitals. Fifty-two percent of the patients (798 577 of 1 543 535) were boys, and 48% (744 958 of 1 543 535) were girls. The median age of patients was 14 years (boys, 13 years; girls, 15 years). The head was the most frequent anatomy examined with CT (876 655 of 1 543 535 examinations [57%]). For head without contrast material CT examinations, the age-based CTDIvol AD ranged from 19 to 46 mGy, and DRL ranged from 23 to 55 mGy, with both AD and DRL increasing with age. For body examinations, DRLs and ADs for size-based CTDIvol, SSDE, and DLP increased consistently with the patient's effective diameter. Conclusion Diagnostic reference levels and achievable doses as a function of patient age and effective diameter were developed for the 10 most commonly performed CT pediatric examinations using American College of Radiology Dose Index Registry data. These benchmarks can guide CT facilities in adjusting pediatric CT protocols and resultant doses for their patients. © RSNA, 2021 An earlier incorrect version appeared online. This article was corrected on October 29, 2021.

Tumour volume distribution can yield information on tumour growth and tumour control

BackgroundIt is shown that tumour volume distributions can yield information on two aspects of cancer research: tumour induction and tumour control. Materials and methodsFrom the hypothesis that the intrinsic distribution of breast cancer volumes follows an exponential distribution, firstly the probability density function of tumour growth time was deduced via a mathematical transformation of the probability density functions of tumour volumes. In a second step, the distribution of tumour volumes was used to model the variation of the clonogenic cell number between patients in order to determine tumour control probabilities for radiotherapy patients. ResultsDistribution of lag times, i.e. the time from the appearance of the first fully malignant cell until a clinically observable cancer, can be used to deduce the probability of tumour induction as a function of patient age. The integration of the volume variation with a Poisson-TCP model results in a logistic function which explains population-averaged survival data of radiotherapy patients. ConclusionsThe inclusion of tumour volume distributions into the TCP formalism enables a direct link to be deduced between a cohort TCP model (logistic) and a TCP model for individual patients (Poisson). The TCP model can be applied to non-uniform tumour dose distributions.

Computer-assisted Reporting and Decision Support Increases Compliance with Follow-up Imaging and Hormonal Screening of Adrenal Incidentalomas

To assess the impact of using a computer-assisted reporting and decision support (CAR/DS) tool at the radiologist point-of-care on ordering provider compliance with recommendations for adrenal incidentaloma workup. Abdominal CT reports describing adrenal incidentalomas (2014 - 2016) were retrospectively extracted from the radiology database. Exclusion criteria were history of cancer, suspected functioning adrenal tumor, dominant nodule size < 1 cm or ≥ 4 cm, myelolipomas, cysts, and hematomas. Multivariable logistic regression models were employed to predict follow-up imaging (FUI) and hormonal screening orders as a function of patient age and sex, nodule size, and CAR/DS use. CAR/DS reports were compared to conventional reports regarding ordering provider compliance with, frequency, and completeness of, guideline-warranted recommendations for FUI and hormonal screening of adrenal incidentalomas using Chi-square test. Of 174 patients (mean age 62.4; 51.1% women) with adrenal incidentalomas, 62% (108/174) received CAR/DS-based recommendations versus 38% (66/174) unassisted recommendations. CAR/DS use was an independent predictor of provider compliance both with FUI (Odds Ratio [OR]=2.47, p = 0.02) and hormonal screening (OR=2.38, p = 0.04). CAR/DS reports recommended FUI (97.2%,105/108) and hormonal screening (87.0%,94/108) more often than conventional reports (respectively, 69.7% [46/66], 3.0% [2/66], both p <0.0001). CAR/DS recommendations more frequently included instructions for FUI time, protocol, and modality than conventional reports (all p <0.001). Ordering providers were at least twice as likely to comply with report recommendations for FUI and hormonal evaluation of adrenal incidentalomas generated using CAR/DS versus unassisted reporting. CAR/DS-directed recommendations were more adherent to guidelines than those generated without.

Combined antibiotic, steroid, and moisturizer for atopic dermatitis: A two‐year case series of patient‐reported outcomes

Eczema treatments that target Staphylococcus aureus include topical mixtures of antimicrobial agent and corticosteroid diluted in a moisturizer base, previously described in the literature as compounded antibacterial, steroid, and moisturizer (CASM). There have been no placebo-controlled blinded studies of CASM. Thus, patient-reported outcome data may prove valuable. To determine the patient-reported clinical course of eczema treatment with CASM. Longitudinal case series between May 2016 and August 2018 of CASM patients/parents. Patients completed surveys including the POEM measure at start of treatment, 1week, 2weeks, 1month, 3months, 6months, 9months, and 12months thereafter. Response curves were fitted to severity measures over time and compared by patient age group; survival analysis was used to estimate time-to-clear status as a function of patient age and initial severity. A total of 2153 reports were received from 728 unique respondents with a median patient age of 7 and range of 0-85. Response curves showed significant improvement over time leading to plateaus between 30 and 60days of treatment. Overall mean improvement between start and day 90 for POEM was 14.3 (from 20.0 [95% CI 11.4-28.8] to 5.7 [95% CI -3.2 to 14.8]). Improvement was seen in each age group. Patient-reported outcomes suggest efficacy of CASM. There were large reductions in POEM scores, mostly in the first 30days of treatment for all age groups.

Pediatric Head CT: Automated Quantitative Analysis with Quantile Regression.

Together with quantile regression methods, such a model would have the potential for clinical utility through automated quantitative comparison of individual cases relative to their age and gender-matched peer group. Our aim was to demonstrate the automated processing of digital clinical head CT data in the development of a clinically useful model of age-related changes of the brain in the first 2 decades of life. A total of 415 (209 female) consecutive, clinical head CTs with radiographically normal findings from patients from birth through 20 years of age were retrospectively selected and subjected to automated segmentation. Brain volume, brain parenchymal fraction, brain radiodensity, and brain radiomass were assessed as a function of patient age. Statistical modeling and quantile regression were performed. Brain volume increased from 400 cm3 at birth to 1350 cm3 at 20 years of age (>3-fold). Males had a slightly steeper growth trajectory than females, with approximately 8% difference in volume between the sexes established in the first few years of life. Brain parenchymal fraction was variable at younger than 2 years of age, stabilizing between 0.85 and 0.92 at 2-3 years of age. Brain mean radiodensity was lower at birth (24 HU) and increased through 3 years of age, after which it stabilized near 30 HU, an approximately 25% increase. The product of brain volume and mean brain radiodensity (radiomass), increased from 700 HU × mL at birth to 3900 HU × mL, a 5.6-fold increase, with approximately 5% difference between males and females at 20 years. Quantile regression enables a given metric to be interpreted relative to an age- and sex-matched peer group. Automated segmentation of clinical head CT images permitted the generation of a reference database for quantitative analysis of pediatric and adolescent brains. Quantile regression facilitates clinical application.

Dosimetric considerations of 99mTc-MDP uptake within the epiphyseal plates of the long bones of pediatric patients

Skeletal scintigraphy is most performed in pediatric patients using the radiopharmaceutical 99mTc labelled methylene diphosphonate (99mTc-MDP). Reference biokinetic models for 99mTc-MDP indicate 50% of the administered activity is uniformly localized to the interior bone surfaces (trabecular and cortical regions), yet imaging data clearly show some preferential uptake to the epiphyseal growth plates of the long bones. To explore the dosimetric consequences of these regional activity concentrations, we have modified mesh-type computational phantoms of the International Commission on Radiological Protection (ICRP) reference pediatric series to explicitly include geometric models of the epiphyseal growth plates (2 mm in thickness) within the left/right, distal/proximal ends of the humeri, radii, ulnae, femora, tibia, and fibulae. Bone mineral activity from the ICRP Publication 128 biokinetic model for 99mTc-MDP (ICRP ) was then partitioned to the growth plates at values of 0.5%, 4.4%, 8.3%, 12.2%, 16.1%, and 20%. Radiation transport simulations were performed to compute 99mTc S-values and organ dose coefficients to the soft tissues and to bone site-specific regions of spongiosa. As the percentage of bone activity assigned to the growth plates was increased (from 0.5% to 20%), absorbed doses to the soft tissue organs, active bone marrow, bone endosteum (BE), as well as the detriment-weighted dose, were shown to decrease from their nominal values (no substantial growth plate activity), while epiphyseal plate self-doses increased. In the 15 year old male phantom, moving from 0.5% to 20% relative bone activity within the epiphyseal plates resulted in a 15% reduction in active marrow (AM) and BE dose, a 10% reduction in mean soft tissue and detriment-weighted dose, and a 6.3-fold increase in epiphyseal plate self-dose. In the newborn female phantom, we observed a 18% decrease in AM and BE dose, a 10% decrease in mean soft tissue dose, a 15% decrease in detriment-weighted dose, and 12.8-fold increase in epiphyseal plate self-dose. Increases (to 3 mm) and decreases (to 1 mm) in the assumed growth plate thickness of our models were shown to impact only the growth plate self-dose. Future work in differential quantification of 99mTc-MDP activity—growth plates versus other bone surfaces—is required to provide clinically realistic data on activity partitioning as a function of patient age, and perhaps skeletal site. The phantom series presented here may be used to develop more optimized age-related guidance on 99mTc-MDP administered activities to children.

Superior therapy response predictions for patients with myelodysplastic syndrome (MDS) using Cellworks Singula: MyCare-009-02.

e19528 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of MDS patients remains relatively poor. Therapy selection is often based on information considering only cytogenetics and single molecular aberrations and ignoring other patient-specific omics data that could potentially enable more effective treatments. The Cellworks Singula™ report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a more accurate predictor of patient-specific therapy response than PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 146 MDS patients aged 28 to 89 years (median 69) treated with PPT. Patient omics data was available from PubMed and TCGA. The accuracy of Singula was compared to that of PPT using McNemar’s test to account for the correlation between Singula and PPT. Multivariate logistic regression modeled complete response (CR) as a function of patient age, PPT, and Singula against any non-response (NR). Likelihood ratio tests were performed to further validate if Singula provides predictive information beyond PPT or patient age. Similar analyses were performed for overall survival (OS) using proportional hazards regression. Results: Singula was a better predictor for CR than PPT (McNemar’s χ2 = 42.0, p-value &lt; 0.0001), with an overall accuracy of 73.3% (Exact 95% CI: 65.3%, 80.2%) compared to 37.7% (95% CI: 30.0%, 46.1%) for PPT. Singula exhibited a sensitivity and specificity of 90.9% (95% CI: 80.0%, 97.0%) and 62.6% (95% CI: 51.8%, 72.6%), respectively. In multivariate regression analysis, Singula (p &lt; 0.0001) remained an independent predictor for CR after adjusting for patient age (p = 0.0759) and PPT (p = 0.0496). Singula provided alternative therapy selections for 17 of 53 true negative detected by Cellworks. Conclusions: Singula is a superior independent predictor for CR compared to PPT in MDS patients. The Singula report can also validate therapy selection, correctly identify non-responders to PPT and further provide alternative therapy selections.

Superior therapy response predictions for patients with acute myeloid leukemia (AML) using Cellworks Singula: MyCare-009-01.

e19502 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of AML patients remains relatively poor. Therapy selection is often based on information considering only cytogenetics and single molecular aberrations and ignoring other patient-specific omics data that could potentially enable more effective treatments. The Cellworks Singula™ report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a more accurate predictor of patient-specific therapy response than PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 494 AML patients aged 2 to 85 years (median 54) treated with PPT. Patient omics data was available from PubMed. The accuracy of Singula was compared to that of PPT using McNemar’s test to account for the correlation between Singula and PPT. Multivariate logistic regression modeled complete response (CR) as a function of patient age, PPT, and Singula against any non-response (NR). Likelihood ratio tests were performed to further validate if Singula provides predictive information beyond PPT or patient age. Similar analyses were performed for overall survival (OS) using proportional hazards regression. Results: Singula was a better predictor for CR than PPT (McNemar’s χ2 = 72.0, p-value &lt; 0.0001), with an overall accuracy of 88.5% (95% CI: 85.3%, 91.1%) compared to 70.2% (95% CI: 66.0%, 74.2%) for PPT. Singula exhibited a sensitivity and specificity of 97.1% and 68.0%, respectively. In multivariate regression analysis, Singula (p &lt; 0.0001) remained an independent predictor for CR after adjusting for patient age (p = 0.0329) while PPT became not significant (p = 0.75). Singula was also an independent predictor for OS (p &lt; 0.0001) after adjusting for patient age (p = 0.0018) and PPT (p = 0.0011). For all 100 true negatives, Singula generated alternative standard of care therapy selections with predicted clinical response. Conclusions: Singula is a superior independent predictor for CR and OS compared to PPT in AML patients. The Singula report can also validate therapy selection, correctly identify non-responders to PPT and further provide alternative therapy selections.