Median Percentage Research Articles

Estimation of Nasal Airway Cross-sectional Area From Endoscopy Using Depth Maps: A Proof-of-Concept Study.

Endoscopy is routinely used to diagnose obstructive airway diseases. Currently, endoscopy is only a visualization technique and does not allow quantification of airspace cross-sectional areas (CSAs). This pilot study tested the hypothesis that CSAs can be accurately estimated from depth maps created from virtual endoscopy videos. Cross-sectional. Academic tertiary medical center. Virtual endoscopy and depth map videos of the nasal cavity were digitally created based on anatomically accurate three-dimensional (3D) models built from computed tomography scans of 30 subjects. A software tool was developed to outline the airway perimeter and estimate the airspace CSA from the depth maps. Two otolaryngologists used the software tool to estimate the nasopharynx CSA and the nasal valve minimal CSA (mCSA) in the left and right nasal cavities. Model validation statistics were performed. Nasopharynx CSA had a median percent error of 3.7% to 4.6% when compared to the true values measured in the 3D models. Nasal valve mCSA had a median percent error of 22.7% to 33.6% relative to the true values. Raters successfully used the software tool to identify subjects with nasal valve stenosis (ie, mCSA < 0.20 cm2) with a sensitivity of 83.3%, specificity ≥ 90.7%, and classification accuracy ≥ 90.0%. Interrater and intrarater agreements were high. This study demonstrates that airway CSAs in 3D models can be accurately estimated from depth maps. The development of artificial intelligence algorithms to compute depth maps may soon allow the quantification of airspace CSAs from clinical endoscopies.

Ultra-processed food consumption and increased risk of metabolic syndrome in Korean adults: A cross-sectional analysis of the KNHANES 2016–2020

ObjectiveThis study aimed to investigate the association between ultra-processed food (UPF) intake and the risk for metabolic syndrome (MetS) in Korean adults. MethodsThe study consisted of 22 688 Korean adults ≥19 y of age from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016–2020. The NOVA classification categorizes foods according to the nature, extent, and purpose of industrial processing. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III criteria and a modified waist circumference cut-off for Korean adults. We estimated the usual percent total food intake from UPFs. We used multivariate logistic regression to assess the association between UPFs and risk for MetS, adjusted for age, sex, education level, income level, smoking status, alcohol drinking, physical activity, and total energy intake. We further analyzed the association of UPFs with each component of MetS. ResultsThe median usual percent total food intake from UPFs was 22%, and the midpoint of intake ranged from 3% (quartile 1) to 48% (quartile 4). The group with the highest UPF consumption had a 19% higher risk for developing MetS than the lowest quartile of UPF consumption (odds ratio [OR],1.19; 95% confidence interval [CI], 1.06–1.33; Ptrend = 0.006). In analysis of the relationship between UPF intake and MetS components, a higher UPF was associated with an increased risk for hypertension (OR, 1.13; 95% CI, 1.01–1.26; Ptrend = 0.037) and abdominal obesity (OR, 1.19; 95% CI, 1.07–1.33; Ptrend = 0.001), but had no significant association with other components (hyperglycemia, hypertriacylglycerolmia, and low high-density lipoprotein cholesterol, all P > 0.05). ConclusionHigher UPF contribution to total daily food intake is associated with an increased risk for MetS, particularly with a higher risk for hypertension and abdominal obesity.

Insomnia with objective but not subjective short sleep duration is associated with incident cardiovascular and/or cerebrovascular disease.

Insomnia with objective short sleep duration (ISSD) has been associated with cardiometabolic outcomes (ie, hypertension or diabetes). We examined whether ISSD, based on objective or subjective sleep measures, is associated with more serious health problems, such as incident cardiovascular and/or cerebrovascular disease (CBVD). 1,258 men and women from the Penn State Adult Cohort (56.9% women, aged 48.3 ± 12.95 years) without CBVD at baseline were followed up for 9.21 ± 4.08 years. The presence of CBVD was defined as a history of diagnosis or treatment of heart disease and/or stroke. Insomnia was defined as a complaint of insomnia with a duration ≥ 1 year. Poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, nonrestorative sleep, or early morning awakening. Objective short sleep duration was defined as < 6 hours' sleep based on polysomnography. Subjective short sleep duration was based on the median self-reported percentage of sleep time (ie, < 7 hours). Compared with normal sleepers with normal sleep duration, the highest risk of incident CBVD was in the ISSD group (odds ratio = 2.46, 95% confidence interval = 1.04-5.79), and the second highest was in normal sleepers with short sleep duration (odds ratio = 1.68, 95% confidence interval = 1.11-2.54). The risk of incident CBVD was not significantly increased in poor sleepers or those with insomnia with normal sleep duration. Finally, insomnia with subjective short sleep duration was not associated with increased incident CBVD. These data add to the cumulative evidence that ISSD, based on objective but not subjective measures, is the more severe biological phenotype of the disorder associated with incident CBVD. Pejovic S, Vgontzas AN, Fernandez-Mendoza J, etal. Insomnia with objective but not subjective short sleep duration is associated with incident cardiovascular and/or cerebrovascular disease. J Clin Sleep Med. 2024;20(7):1049-1057.

Factors associated with reporting left ventricular ejection fraction with 3D echocardiography in real-world practice.

Guidelines recommend 3D echocardiography (3DE) to assess left ventricular ejection fraction (LVEF) on transthoracic echocardiogram (TTE) when possible, but it is unclear which factors are most strongly associated with reporting 3DE LVEF in real-world practice. We evaluated 3DE LVEF reporting by age, sex, BMI, TTE location and variation in reporting by sonographer and reader. All TTEs were performed without contrast enhancement agent at a large medical center from 9/2015 to 12/2020 using ultrasound machines capable of 3DE. We used multivariable logistic regression to assess which factors were most associated with reporting 3DE LVEF. Among 35641 TTEs included in this study, 57.4% were performed on women. 3DE LVEF was reported on 18391 TTEs (51.6% of cohort; 50.5% for women and 52.4% for men). Portable inpatient TTEs (n=5569) had the lowest rates of 3DE LVEF reporting (30.9%), while general outpatient TTEs (n=15933) had greater reporting (56.9%). Outpatient TTEs with an indication for chemotherapy (n=3244) had the highest rates of 3DE LVEF (87.2%). The median (IQR) percentage of TTEs reporting 3D LVEF was 52.7% (43.1%-68.1%) among sonographers and 51.6% (46.5%-59.6%) among readers. Among 20082 (56.3%) TTEs with 3DE LVEF measured by sonographers, 91.6% were included by readers in the final report. After adjustment, performing sonographer in the highest reporting quartile was most strongly associated with reporting 3DE LVEF (OR 7.04, 95% CI 6.55-7.56), while an inpatient portable study had the strongest negative association for reporting (OR .38, 95% CI .35-.40). Use of 3DE LVEF in real-world practice varies substantially based on performing sonographer and is low for hospitalized patients, but can be frequently used for chemotherapy. Initiatives are needed to increase sonographer 3DE acquisition in most clinical settings.

Abstract B011: Lower incidence of small intestinal adenocarcinomas may be due to constrained copy number karyotype and increased immune surveillance

Abstract Aim: To evaluate the genomic profiles of duodenal adenocarcinomas and explore the role of the immune system in the evolution of these cancers. Introduction: Tumours of the small intestine are rare and represent the smallest fraction of all gastrointestinal (GI) cancers despite being the largest organ in the GI tract. As a result, they have not been well characterised at the molecular level, and consequently are often clinically managed similarly to colorectal cancers. Methods: Here we performed shallow whole-genome sequencing (sWGS) on 125 cases of the most common adenocarcinomas in the small intestine, duodenal adenocarcinomas, and compared their somatic copy number aberrations to 880 upper and lower GI primary adenocarcinomas from the TCGA. Furthermore, we reanalysed published whole exome sequencing (WEX) from a further 91 small intestinal carcinomas to assess the immune landscape. Results: In our sWGS cohort, we found that duodenal adenocarcinomas have a significantly lower incidence of genome doubling (20%) than elsewhere in the GI tract (colon=43.6%, stomach=44%, rectum=55%, oesophagus=64.3%). Percentage of genome altered (PGA) is affected by the amount of genome doubling present, by median centering the proportion of the genome altered we could circumvent this. Duodenal cancers also had a significantly lower median centered percentage genome aberrated (mPGA) than colon (p=6.3 × 10-4, es=0.176), rectal (p=3 × 10-5, es=0.279), stomach (p=1.5 × 10-8, es=0.309) and oesophageal (p=1.2 × 10-11, es=0.546) adenocarcinomas. Inter-tumour heterogeneity of copy number alterations was lowest in duodenal cancers compared to other GI cancer types (p&amp;lt;2.22 × 10-16 for all and effect size &amp;gt; 0.7 for all). Within the previously published WEX cohort of small intestinal adenocarcinomas, we observed a higher proportion of clonal mutations that are neoantigens (vs not-neoantigens) in immune escaped tumours than non-escaped tumours (p=0.016) and found that small intestinal tumours are more likely to be immune escaped than colon cancers. Escaped small intestinal tumours were associated with a significantly decreased overall survival compared to non-escaped tumours (HR 2.197 (95% CI, 1.736– 46.63); p=0.009). Further, dNdS analysis indicated strong immune-mediated negative selection on clonal non-synonymous mutations in the immunopeptidome in most tumours. Conclusions: The decreased inter-tumour heterogeneity of karyotypes amongst small intestinal cancers compared to other GI cancers could indicate more restricted routes for karyotype evolution in the small intestine. Our data also suggest a more pertinent role for immune-predation than elsewhere in the GI tract. Together this may explain their lower incidence. Citation Format: Salpie Nowinski, Vickna Balarajah, Ann-Marie Baker, Riku Katainen, Christine Hughes, Qingli Guo, Luis Zapata, Eszter Lakatos, Hemant M. Kocher, Trevor A. Graham. Lower incidence of small intestinal adenocarcinomas may be due to constrained copy number karyotype and increased immune surveillance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B011.

Ultrahigh-Spatial-Resolution Photon-counting Detector CT Angiography of Coronary Artery Disease for Stenosis Assessment.

Background Coronary CT angiography is a first-line test in coronary artery disease but is limited by severe calcifications. Photon-counting-detector (PCD) CT improves spatial resolution. Purpose To investigate the effect of improved spatial resolution on coronary stenosis assessment and reclassification. Materials and Methods Coronary stenoses were evaluated prospectively in a vessel phantom (in vitro) containing two stenoses (25%, 50%), and retrospectively in patients (in vivo) who underwent ultrahigh-spatial-resolution cardiac PCD CT (from July 2022 to April 2023). Images were reconstructed at standard resolution (section thickness, 0.6 mm; increment, 0.4 mm; Bv44 kernel), high spatial resolution (section thickness, 0.4 mm; increment, 0.2 mm; Bv44 kernel), and ultrahigh spatial resolution (section thickness, 0.2; increment, 0.1 mm; Bv64 kernel). Percentages of diameter stenosis (DS) were compared between reconstructions. In vitro values were compared with the manufacturer specifications of the phantom and patient results were assessed regarding effects on Coronary Artery Disease Reporting and Data System (CAD-RADS) reclassification. Results The in vivo sample included 114 patients (mean age, 68 years ± 9 [SD]; 71 male patients). In vitro percentage DS measurements were more accurate with increasing spatial resolution for both 25% and 50% stenoses (mean bias for standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 10.1%, 8.0%, and 2.3%; P < .001). In vivo results confirmed decreasing median percentage DS with increasing spatial resolution for calcified stenoses (n = 161) (standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 41.5% [IQR, 27.3%-58.2%], 34.8% [IQR, 23.7%-55.1%], and 26.7% [IQR, 18.6%-44.3%]; P < .001), whereas noncalcified (n = 13) and mixed plaques (n = 19) did not show evidence of a difference (P ≥ .88). Ultrahigh-spatial-resolution reconstructions led to reclassification of 62 of 114 (54.4%) patients to lower CAD-RADS category than that assigned using standard resolution. Conclusion In vivo and in vitro coronary stenosis assessment improved for calcified stenoses by using ultrahigh-spatial-resolution PCD CT reconstructions, leading to lower percentage DS compared with standard resolution and clinically relevant rates of reclassification. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by McCollough in this issue.

Pre-surgical factors related to latent trajectories of 5-year weight loss for a diverse bariatric surgery population

BackgroundAnalyzing trajectories of weight loss may address how particular groups of patients respond to metabolic and bariatric surgery. ObjectivesThe Bariatric Experience Long Term (BELONG) study was designed to use a theoretical model to examine determinants of weight loss and recurrence. SettingLarge integrated health system in Southern California with 11 surgical practices and 23 surgeons. MethodsA total of n = 1338 patients who had metabolic and bariatric surgery were surveyed before surgery to measure factors related to median percent total weight loss (%TWL) over 5 years. Longitudinal weight data were available for n = 1024 (76.5% of the sample). Data were analyzed using latent growth mixture models (GMM) to estimate trajectories of weight change separately for gastric sleeve and bypass operations. These trajectories were then described using relevant variables from the baseline survey. ResultsFor both gastric sleeve (n = 733) and bypass (n = 291) operations, 3 latent trajectories of median %TWL were found corresponding to most, moderate, and least %TWL. Sleeve trajectories were distinguished by body mass index at surgery and geocoded environmental factors. Bypass trajectories varied by self-reported and geocoded environmental factors, comorbidity burden, race, experiential avoidance, and weight control strategies. ConclusionsFuture research should examine the role of the built and perceived environment in surgical weight loss. Bariatric practices should focus less on the presurgical period for predictors of long-term weight loss and begin efforts to monitor real-time patient-reported outcomes to help tailor intervention strategies for patients who either do not lose an expected amount of weight or who begin to experience weight recurrence.

Assessment on the use of allopurinol to improve safety and efficacy of mercaptopurine in pediatric patients with Acute Lymphoblastic Leukemia and Lymphoma during maintenance therapy.

Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed to be the primary contributor to myelosuppression and immunosuppressive effects, while 6-methylmercaptopurine (6-MMPN) is believed to be responsible for several toxicities including hepatotoxicity, pancreatitis, and hypoglycemia. Previous reports suggest the addition of allopurinol may reduce these toxicities. To assess the use of allopurinol to improve both safety and efficacy of mercaptopurine in pediatric patients with ALL and LLy during maintenance therapy. Secondary objectives included evaluating patient tolerability and skewed metabolism. In addition, we also analyzed mercaptopurine daily dose reduction upon allopurinol initiation. The primary endpoint was time within goal ANC prior to and after initiation of allopurinol. Secondary endpoints included; improvement in selective toxicities (hepatotoxicity, pancreatitis, and hypoglycemia) and 6-MMPN to 6-TGN ratio prior to and after allopurinol initiation. In addition, an exploratory endpoint assessing mercaptopurine daily dose reduction prior to and after allopurinol initiation was included. Sixteen patients met inclusion criteria and 15 (94%) of which were included in this study. Median percent of maintenance days within goal ANC prior to and after initiation of allopurinol was 27.8 (IQR 22.6-44.9) and 41.6 (IQR 20.2-58.2) respectively. All patients experienced selective toxicities; 15 (100%) hepatotoxicity, 1 (7%) pancreatitis, and 3 (20%) hypoglycemia. Improvement of toxicities was seen in 13/15 (87%), 1/1 (100%), and 2/3 (67%) respectively. Average 6-MMPN:6-TGN ratio prior to allopurinol initiation was 304:1 and after, allopurinol initiation improved to 15:1, resulting in a 95% reduction. Average mercaptopurine dose prior to and after allopurinol initiation decreased by about 56% (63 to 28 mg/m2 /day). Results suggest that the use of allopurinol in pediatric patients with ALL and LLy receiving mercaptopurine during maintenance therapy is both safe and effective.

Assessment of the condylar response of two differently anchored fixed functional appliances in class II malocclusion in young adult orthodontic patients: A randomized clinical trial.

Measuring the condylar volume changes after treatment with skeletally anchored type IV Herbst appliance vs. Twin Force Bite Corrector (TFBC) in class II malocclusion in young adult patients. Twenty class II malocclusion participants were randomly involved in our randomized clinical study. They are divided equally into two groups: group I (10 patients with an age range of 16 to 18 years and a mean age of (17.15 ± 0.62) (five males and five females) with a mean Angle formed between (A) point and (Nasion) point and (B) point, to determine anteroposterior relation between maxilla and mandible (ANB) of 6.20 (1.03) and a mean mandibular length of 106.1 (1.7), who were treated by a skeletally anchored type IV Herbst appliance, supported at the mandible by two mini-plates fixed bilaterally at the mandibular symphysis; group II (10 patients with an age range of 15 to 18 years and a mean age of (16.85 ± 0.33) (six males and four females) with a mean ANB of 6.80 (0.89) and a mean mandibular length of 107.3 (2.36), who were treated by a TFBC that was installed just mesial to the tube of the maxillary first permanent molar and distal to the bracket of the lower canine for 4 months. According to the Index of Orthognathic Functional Treatment Need (IOFTN) index, the participants in both groups have grade 4 (great need for treatment) as they have excessive overjet (6-9 mm). Cone-beam computed tomography (CBCT) was taken just before installing fixed functional appliances and after the removal. The condylar volume was measured using Dolphin software. Parametric measurements were performed by the independent t-test, while non-parametric variables (percent change) were compared by the Mann-Whitney U-test. On the right side, the Herbst group recorded a percent increase (median = 1.23%), while TFBC recorded a median percent decrease (-7.85%). This change is statistically significant (P = 0.008). The difference in the condylar volume was significantly higher with the mini-plate anchored Herbst appliance than with the dentally anchored TFBC group.

Canine primary liver tumors treated with stereotactic body radiation therapy: A case series.

Stereotactic body radiation therapy (SBRT) is an increasingly used alternative treatment option for nonresectable hepatocellular carcinoma (HCC) in people. Comparatively, the publication of SBRT of dogs with HCC is limited. The objective of this retrospective, descriptive case series was to evaluate the clinical outcomes and toxicity data of SBRT in dogs with HCC and imaging-documented primary liver tumors using volumetric-modulated arc therapy delivery at two private institutions. Medical records of 14 dogs treated between 2018 and 2023 were reviewed. All dogs had macroscopic tumors, and 9 of 14 dogs had HCC diagnoses confirmed on cytology or histopathology. The median longest tumor diameter was 5.5cm. The median percentage of planning target volume relative to liver volume was 27.1%. Most dogs were treated with three daily fractions of 7-7.5Gy. All dogs completed their radiotherapy protocols. Three of nine HCC dogs experienced partial responses and clinical improvement. Five of nine HCC dogs had stable disease. Overall median survival time was 164 days for nine HCC dogs (range: 93-706 days). One late grade 5 liver and two late grade 3 kidney side effects were reported. One dog received repeated SBRT to the same HCC treatment field, and one dog had two courses of SBRT to bifocal HCC treatment fields, both with no more than grade 2 acute and chronic toxicities.

Ketamine for Primary Analgosedation in Critically Ill Surgery and Trauma Patients Requiring Mechanical Ventilation.

Evaluate effectiveness and safety outcomes associated with the use of ketamine for primary analgosedation in the surgical/trauma ICU setting. Retrospective cohort study. Academic medical center in Minnesota. Patients admitted to the surgical ICU between 2015 and 2019 requiring mechanical ventilation and meeting one of three definitions for ketamine primary analgosedation were included: 1) no concomitant opioid infusion, 2) ketamine monotherapy for greater than or equal to 6 hours with subsequent opioid infusion, or 3) ketamine initiated concomitantly or within 4 hours of opioid and total opioid duration less than 4 hours. None. Use of ketamine, analgesics, and sedatives were evaluated. Pain, sedation, and delirium assessments immediately before and during ketamine infusion were collected and compared with reported goals. Concomitant analgesics, sedatives, and psychotropics were recorded. Reported failures due to ineffectiveness and toxicity were collected. Of 164 included patients, 88% never received a concomitant opioid infusion (primary analgosedation definition 1), 12% met alternative criteria for primary analgosedation (definitions 2 and 3). A majority, 68%, were surgical admissions and mean Acute Physiology and Chronic Health Evaluation III score was 90 (± 30). Median mechanical ventilation duration was 2.5 days (1.1-4.5) and ICU length of stay of 4.9 days (3-8). The median ketamine infusion dose and duration were 0.18 mg/kg/hr (0.1-0.3) and 30 hours (15.1-51.8). Concomitant infusions of propofol and dexmedetomidine were administered in 49% and 29% of patients, respectively. During ketamine infusion, the median percent of total pain scores at goal was 62% (33-96%), while 64% (37-91%) of Richmond Agitation Sedation Scale scores were at goal, and 47% of patients were Confusion Assessment Method-ICU positive during the ketamine infusion. Hallucinations were documented in 14% of patients and ketamine failure occurred in 11% of patients. Ketamine may be an effective primary analgosedation option in intubated surgical ICU patients, but prospective randomized studies are needed to evaluate this strategy.

P835 Acceptability, feasibility, and adherence of an emulsifier-free diet in healthy volunteers

Abstract Background Emulsifiers are associated with intestinal inflammation and therefore excluded in new dietary strategies in inflammatory bowel diseases (IBD). We aimed to investigate the feasibility, acceptability, and adherence of an emulsifier-free diet (EFD) in healthy volunteers as part of the FOod Additives on the Mucosal barrier (FOAM) study. Methods We recruited 60 healthy volunteers to a 7-week interventional trial. After 1 baseline week of their habitual diet, participants followed an EFD for 6 weeks. Participants were instructed on how to follow an EFD yet were not advised on ultra-processed food (UPF) reduction. Every 2 weeks after starting the EFD (week 2, 4, and 6), subjects were asked about their experience on a 12-item questionnaire, including 5-point Likert scales, open-ended and multiple answer-type questions. Food logs were kept in the smartphone application 'Fatsecret', including photographs to capture brand names. Manual calculation of all days with plausible energy intakes (800-4200 kcals per day for men and 600-3500 kcals for women) for at least 79.5% of the time was performed to exclude incomplete reporting. Emulsifier intake was measured as number of servings of emulsifier-containing foods. Adherence rate was calculated as a percentage of mistake-free days. Results Of the 60 healthy volunteers, 2 were excluded due to NSAID use. Median (IQR) age was 25.5 years (23.0-33.0), median BMI was 22.7 kg/m2 (21.2-25.6) and 19.0% were male. Median percentage of plausible food logs was 100% (98.0-100%), and 1 subject was excluded due to inadequate dietary reporting. During the EFD, emulsifier intake significantly decreased (baseline vs week 1; p=2.3x10-9, vs week 6; p=5.3x10-9, Figure 1A), as well as UPF consumption according to the NOVA classification (baseline vs week 1; p=5.6x10-7, vs week 6; p=1.6x10-7, Friedman test with post-hoc paired Wilcoxon, Figure 1B). The adherence rate to the EFD was very high (median 88.1%, IQR 76.2-95.2%). Median number of mistakes during the EFD was 6 (2-14), for a median number of 3 selected food items (1-5). Most mistakes were made in the categories of dairy-like products, meat products, and bakery goods. The top 3 reported challenges included restricted food choices, checking food labels, and longer shopping times (Table 1). At week 6, For 70.7% the EFD was tasty to very tasty and for 72.4% it was acceptable to very acceptable. Hot meals and snacks were the most challenging meal types. Conclusion In this 7-week interventional trial in 60 healthy volunteers, adhering to an EFD was feasible and acceptable. While following the EFD, an inadvertent and stable decrease in UPF intake was noted. These finding represent important considerations when designing future dietary trials in IBD.

P417 1 year follow-up of pediatric ulcerative colitis using intestinal ultrasound

Abstract Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been limited to small samples of patients with no long-term follow up. Our aim is to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings. Methods Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit. Results 42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (p&amp;lt;0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (p&amp;lt;0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (&amp;gt;250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months. Conclusion BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity.

Optimization of collimator angle combined island blocking with parked gap achieves superior normal tissue sparing in SBRT planning of multiple liver lesions.

To propose an efficient collimator angle optimization method by combining island blocking (IB) and parked gap (PG) problem to reduce the radiotherapy dose for normal tissue. The reduction will be done with single-isocenter multi-lesion volumetric modulated arc therapy (VMAT) for the stereotactic body radiation therapy (SBRT) of liver cancer. A novel collimator angle optimization algorithm was developed based on the two-dimensional projection of targets on a beam's eye view (BEV) plane as a function of gantry and collimator angle. This optimization algorithm minimized the sum of the combined IB and PG (IB & PG) areas from all gantry angles for each arc. For comparison, two SBRT plans were respectively generated for each of the 20 retrospective liver cancer cases with multiple lesions. One plan was optimized using the IB & PG algorithm, and the other plan was optimized with a previously reported optimization algorithm that only considered the IB area. Plans were then evaluated and compared using typical dosimetric metrics. With the comparable target coverage, IB & PG plans had significantly lower D500cc, D700cc, mean dose (Dmean), and V15 of normal liver tissues when compared to IB plans. The median percent reductions were 3.32% to 5.36%. The D1cc, D5cc, and Dmean for duodenum and small intestine in IB & PG plans were significantly reduced in a range from 7.60% up to 16.03%. Similarly, the median integral dose was reduced by 3.73%. Furthermore, the percentage of normal liver Dmean sparing when IB & PG plans compared to IB plans, was found to be positively correlated (ρ=0.669, P=0.001) with the inter-target distance. The proposed IB & PG algorithm has been demonstrated to outperform the IB algorithm in almost all normal tissue sparing, and the magnitude of liver sparing was positively correlated with inter-target distance.

Association between changes in prices and out-of-pocket costs for brand-name clinician-administered drugs.

To determine whether annual changes in prices for clinician-administered drugs are associated with changes in patient out-of-pocket costs. National commercial claims database, 2009 to 2018. In a serial, cross-sectional study, we calculated the annual percent change in manufacturer list prices and net prices after rebates. We used two-part generalized linear models to assess the relationship between annual changes in price with (1) the percentage of individuals incurring any out-of-pocket costs and (2) the percent change in median non-zero out-of-pocket costs. We created annual cohorts of privately insured individuals who used one of 52 brand-name clinician-administered drugs. List prices increased 4.4%/yr (interquartile range [IQR], 1.1% to 6.0%) and net prices 3.3%/yr (IQR, 0.3% to 5.5%). The median percentage of patients with any out-of-pocket costs increased from 38% in 2009 to 48% in 2018, and median non-zero annual out-of-pocket costs increased by 9.6%/yr (IQR, 4.1% to 15.4%). There was no association between changes in prices and out-of-pocket costs for individual drugs. From 2009 to 2018, prices and out-of-pocket costs for brand-name clinician-administered drugs increased, but these were not directly related for individual drugs. This may be due to changes to insurance benefit design and private insurer drug reimbursement rates.

Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study

BackgroundSoluble urokinase plasminogen activator receptor is an inflammatory biomarker that may prognosticate cardiovascular outcomes. We sought to determine the associations between soluble urokinase plasminogen activator receptor and established markers of cardiotoxicity in breast cancer patients receiving doxorubicin.MethodsWe conducted a prospective cohort study of women with newly diagnosed breast cancer receiving standard-dose doxorubicin (240 mg/m2) at Rush University Medical Center and Rush Oak Park Hospital (Chicago, IL) between January 2017 and May 2019. Left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers (N-terminal prohormone B-type natriuretic peptide, troponin-I, and high-sensitivity C-reactive protein) were measured at baseline and at intervals up to 12-month follow-up after end of treatment. The associations between soluble urokinase plasminogen activator receptor and these endpoints were evaluated using multivariable mixed effects linear regression.ResultsOur study included 37 women (mean age 47.0 ± 9.3 years, 60% white) with a median baseline soluble urokinase plasminogen activator receptor level of 2.83 ng/dL. No participant developed cardiomyopathy based on serial echocardiography by one-year follow-up. The median percent change in left ventricular strain was -4.3% at 6-month follow-up and absolute changes in cardiac biomarkers were clinically insignificant. There were no significant associations between soluble urokinase plasminogen activator receptor and these markers of cardiotoxicity (all p > 0.05).ConclusionsIn this breast cancer cohort, doxorubicin treatment was associated with a very low risk for cardiotoxicity. Across this narrow range of clinical endpoints, soluble urokinase plasminogen activator receptor was not associated with markers of subclinical cardiotoxicity. Further studies are needed to clarify the prognostic utility of soluble urokinase plasminogen activator receptor in doxorubicin-associated cardiomyopathy and should include a larger cohort of leukemia and lymphoma patients who receive higher doses of doxorubicin.

Enhancing Patient Selection in Stage IIIA-IIIB NSCLC: Invasive Lymph Node Restaging after Neoadjuvant Therapy.

Restaging of mediastinal lymph nodes plays a crucial role in the multimodal treatment of stage IIIA Non-Small-Cell Lung Cancer (NSCLC). This study aimed to assess the impact of restaging using endobronchial ultrasound (EBUS), endoesophageal ultrasound (EUS), and transcervical extended mediastinal lymphadenectomy (TEMLA) after neoadjuvant chemotherapy (CHT) or chemoradiotherapy (CRT) on the 5-year overall survival (OS) of patients with NSCLC diagnosed with clinical stage IIIA-IIIB and metastatic ipsilateral mediastinal nodes (N2) who underwent radical pulmonary resections. Patients diagnosed with stage IIIA-IIIB NSCLC and N2 mediastinal nodes were included in this study. Restaging of mediastinal lymph nodes was performed using EBUS, EUS, and TEMLA. The patients were divided into two groups based on the restaging method: the TEMLA restaging group and the chest CT scan-only group. The primary outcome measure was the 5-year OS rate, and the secondary outcome measures included median OS and survival percentages. Statistical analysis, including the log-rank test, was conducted to assess the differences between the two groups. The TEMLA restaging group demonstrated significantly better overall survival compared to the chest CT scan-only group (log-rank test, p = 0.02). This was evident through a four-fold increase in median OS (59 vs. 14 months) and a higher 5-year OS rate of 55.9% (95% CI: 40.6-71.1) compared to 25.0% (95% CI: 13.7-36.3) in the chest CT scan-only group (p = 0.003). Invasive restaging of mediastinal lymph nodes improves the selection of patients with stage IIIA-IIIB (N2) NSCLC after neoadjuvant therapy. The use of EBUS, EUS, and TEMLA provides valuable information for identifying patients who may benefit from surgery by identifying N2 to N0-1 downstaging. These findings emphasize the importance of incorporating restaging procedures into the treatment decision-making process for NSCLC patients with mediastinal lymph node involvement.

Stabilizing the Proteomes of Acute Myeloid Leukemia Cells: Implications for Cancer Proteomics

Previous work has shown that inhibition of abundant myeloid azurophil granule-associated serine proteases (ELANE [neutrophil elastase], PRTN3 [protease 3], and CTSG [Cathepsin G]) is required to stabilize some proteins in myeloid cells. We therefore hypothesized that effective inhibition of these proteases may be necessary for quantitative proteomic analysis of samples containing myeloid cells. To test this hypothesis, we thawed viably preserved acute myeloid leukemia cells from cryovials in the presence or the absence of diisopropyl fluorophosphate (DFP), a cell-permeable and irreversible serine protease inhibitor. Global proteomic analysis was performed, using label-free and isobaric peptide-labeling quantitation. The presence of DFP resulted in an increase of tryptic peptides (14–57%) and proteins (9–31%). In the absence of DFP, 11 to 31% of peptide intensity came from nontryptic peptides; 52 to 75% had cleavage specificity consistent with activities of ELANE–PRTN3. Treatment with DFP reduced the intensity of nontryptic peptides to 4-8% of the total. ELANE inhibition was 95%, based on diisopropyl phosphate modification of active site serine residue. Overall, the relative abundance of 20% of proteins was significantly altered by DFP treatment. These results suggest that active myeloid serine proteases, released during sample processing, can skew quantitative proteomic measurements. Finally, significant ELANE activity was also detected in Clinical Proteomics Tumor Analysis Consortium datasets of solid tumors (many of which have known myeloid infiltration). In the pancreatic cancer dataset, the median percentage of nontryptic intensity detected across patient samples was 34%, with many patient samples having more than half of their detected peptide intensity from nontryptic cleavage events consistent with ELANE-PRTN3 cleavage specificity. Our study suggests that in vitro cleavage of proteins by myeloid serine proteases may be relevant for proteomic studies of any tumor that contains infiltrating myeloid cells.

Regional Variation in Antenatal Late Preterm Steroid Use Following the ALPS Trial

The publication of the Antenatal Late Preterm Steroids (ALPS) trial in February 2016 demonstrated that antenatal administration of betamethasone in the late preterm period (between 34 to 36 weeks of gestation) for individuals with a high risk of delivery decreased neonatal respiratory morbidity. National estimates have suggested the trial did change obstetric practice, but little is known if the evidence was adopted uniformly or equitably. To assess regional variation in the use of late preterm steroids after the publication of the Antenatal Late Preterm Steroids (ALPS) Trial and to understand factors associated with a region's pace of adoption. This cross-sectional study used US natality data from February 2015 to October 2017 from hospital referral regions (HRRs) within the US. Inclusion criteria included live-born, nonanomalous, singleton, late preterm (34 to 36 completed weeks of gestation) neonates born to individuals without pregestational diabetes. This study was conducted from November 15, 2022, to January 13, 2023. HRRs were categorized as either a slower adopter or faster adopter of antenatal late preterm steroids based on the observed vs expected pace of antenatal steroid adoption in a 1-year period after the trial's dissemination. Patient and regional factors hypothesized a priori to be associated with the uptake of late preterm steroids were compared between faster and slower adopters. Comparisons were made using Student t test or Wilcoxon rank-sum test, as appropriate. A multivariable logistic regression was constructed to identify factors associated with faster adopter status in the postperiod. There were 666 097 late preterm births in 282 HRRs. The mean (SD) maternal age in HRRs was 27.9 (1.2) years. The median (IQR) percentage of births by race categories in HRRs for patients identifying as American Indian or Alaskan Native was 0.5% (0.2%-1.3%); Asian or Pacific Islander, 3.0% (1.7%-5.3%); Black, 12.9% (5.1%-29.1%); and White, 78.6% (66.6%-87.0%). The median percentage of births in HRRs to patients of Hispanic ethnicity was 11.2% (6.3%-27.4%). In this study, 136 HRRs (48.2%) were classified as faster adopters and 146 (51.8%) were classified as slower adopters. Faster adopters increased their steroid use by 12.1 percentage points (from 5.9% to 18.0%) compared with a 5.5 percentage point increase (from 3.7% to 9.2%) among slower adopters (P < .001). Most examined patient and regional factors were not associated with a region's pace of adoption, with the exception of the regional prevalence of prior preterm birth (adjusted odds ratio [aOR], 2.04 [95% CI, 1.48-2.82]) and the percentage of deliveries at 34 to 35 weeks of gestation (aOR, 0.68 [95% CI, 0.47-0.99]) compared with 36 weeks. In this cross-sectional study, there was widespread geographic variation in the adoption of antenatal steroid administration for late preterm births that largely remained unexplained by population factors. These findings should prompt further investigations to barriers to timely or equitable access to new evidence-based practices and guide future dissemination strategies with the goal of more uniform adoption.

The Bronchodilator Potential of Astragalus sarcocolla: An in vitro Experiment.

To evaluate the bronchodilatory mechanism of Astragalus sarcocolla (ASE) extract on tracheal smooth muscles of rabbits. In-vitro experimental study. Place and Duration of the Study: The animal house of CMH Lahore Medical College, Lahore, and Institute of Dentistry, NUMS, from October 2022 to May 2023. Six rabbits were randomly divided into four groups. After euthanising the rabbit, the trachea was carefully dissected out and stabilised in Kreb's Henseleit solution for 30 minutes and then, stimulated by acetylcholine (Ach) 1µm, under mimicked physiological conditions. Group I served as the control group with tracheal smooth muscles stabilised with 1g tension. In Group II (positive control), tracheal smooth muscles were stimulated by potassium chloride (KCl) (80 mM and 25 mM, respectively) to get maximum tracheal smooth muscle contractions. Later, the tissue was exposed to theophylline with three molar concentrations 0.2, 0.4, 0.6, and 0.8 mM, and cumulative dose response curves were formed. In Group III (ASE group), tracheal smooth muscles were stimulated by KCl (80 mM and 25 mM) and was exposed to increasing concentration of ASE. In group IV, tissue was stimulated by KCl (25 mM) and glibenclamide (3 µM), later exposed to increasing concentration of ASE to confirm the bronchodilatory mechanism. The change in isometric contraction of the tissue was recorded using the force displacement transducer connected to a PowerLab data acquisition system. Concentration response curves were drawn, and median effective concentrations (EC50 values) and percentage inhibition were calculated. Non-linear regression was applied for the analysis of the concentration-response curves. ASE inhibited the KCl-induced low potassium (25 mM) contractions (EC50 = 0.38 mg/ml, 95% CI: 0.04 - 0.38, n = 6). It only partially inhibited the high potassium-induced contractions in tracheal smooth muscles. Pretreatment with glibenclamide showed a rightward shift of the dose-response curve. Theophylline and ASE significantly reduced the low K+ induced smooth muscle contractions in comparison to the control group (p <0.001, each). Astragalus sarcocolla extract produced bronchodilator effects through the activation of ATP sensitive potassium channels in isolated rabbit trachea. Astragalus sarcocolla, Bronchodilators, ATP-sensitive potassium channels, Effective concentration 50, Concentration response curves.