Reliability of MR Enterography Features for Describing Fibrostenosing Crohn Disease.

Background Clinical decision making and drug development for fibrostenosing Crohn disease is constrained by a lack of imaging definitions, scoring conventions, and validated end points. Purpose To assess the reliability of MR enterography features to describe Crohn disease strictures and determine correlation with stricture severity. Materials and Methods A retrospective study of patients with symptomatic terminal ileal Crohn disease strictures who underwent MR enterography at tertiary care centers (Cleveland Clinic: September 2013 to November 2020; Mayo Clinic: February 2008 to March 2019) was conducted by using convenience sampling. In the development phase, blinded and trained radiologists independently evaluated 26 MR enterography features from baseline and follow-up examinations performed more than 6 months apart, with no bowel resection performed between examinations. Follow-up examinations closest to 12 months after baseline were selected. Reliability was assessed using the intraclass correlation coefficient (ICC). In the validation phase, after five features were redefined, reliability was re-estimated in an independent convenience sample using baseline examinations. Multivariable linear regression analysis identified features with at least moderate interrater reliability (ICC ≥0.41) that were independently associated with stricture severity. Results Ninety-nine (mean age, 40 years ± 14 [SD]; 50 male) patients were included in the development group and 51 (mean age, 45 years ± 16 [SD]; 35 female) patients were included in the validation group. In the development group, nine features had at least moderate interrater reliability. One additional feature demonstrated moderate reliability in the validation group. Stricture length (ICC = 0.85 [95% CI: 0.75, 0.91] and 0.91 [95% CI: 0.75, 0.96] in development and validation phase, respectively) and maximal associated small bowel dilation (ICC = 0.74 [95% CI: 0.63, 0.80] and 0.73 [95% CI: 0.58, 0.87] in development and validation group, respectively) had the highest interrater reliability. Stricture length, maximal stricture wall thickness, and maximal associated small bowel dilation were independently (regression coefficients, 0.09-3.97; P < .001) associated with stricture severity. Conclusion MR enterography definitions and scoring conventions for reliably assessing features of Crohn disease strictures were developed and validated, and feature correlation with stricture severity was determined. © RSNA, 2024 Supplemental material is available for this article. See also the article by Rieder and Ma et al in this issue. See also the editorial by Galgano and Summerlin in this issue.

Mortality Risks and Causes in Previous Carbon Monoxide Poisoning: A Nationwide Population-Based Cohort Study.

OBJECTIVES: Carbon monoxide (CO) poisoning can cause brain, heart, and kidney injuries. We aimed to determine the association of risks of all-cause and cause-specific mortality in patients with previous CO poisoning. DESIGN, SETTING, AND PATIENTS: This population-based cohort study used data from the National Health Insurance Service database and the National Death Registry of Korea. Adult patients diagnosed with CO poisoning and controls between 2002 and 2020 were included. Patients were matched with controls on a 1:1 ratio, considering age, sex, insurance type, income level, residential location, smoking status, alcohol consumption, obesity status, medical and psychiatric illness history, and Charlson Comorbidity Index at the index date. The cohort was monitored from 2002 to 2022 or until death or emigration in terms of all-cause and cause-specific mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 48,600 patients with CO poisoning and matched controls were included. The cohort included 41.30% females, and the mean age was 48.05 years. Patients with CO poisoning exhibited a substantially elevated risk of all-cause mortality compared with those in the control group, with an adjusted hazard ratio (aHR) of 15.67 (95% CI, 12.58-19.51). The mortality associated with infectious (aHR, 6.71; 95% CI, 1.51-29.72), neoplasm/oncologic (aHR, 5.20; 95% CI, 3.39-7.99), endocrine (aHR, 13.44; 95% CI, 1.76-102.70), neurologic (aHR, 7.42; 95% CI, 2.91-18.90), cardiovascular (aHR, 8.97; 95% CI, 5.05-15.93), respiratory (aHR, 17.54; 95% CI, 5.48-56.17), and gastrointestinal (aHR, 24.72; 95% CI, 3.34-182.69) disorders was significantly greater in the former. Deaths due to external causes, including suicide, were significantly higher in the CO poisoning group (aHR, 50.07; 95% CI, 30.98-80.90). CONCLUSIONS: Patients with CO poisoning exhibited a heightened risk of all-cause mortality compared with the matched controls. Additionally, the cause-specific mortality risk differed between the groups.

Infrapopliteal Segments on Lower Extremity CTA: Prospective Intraindividual Comparison of Energy-Integrating Detector CT and Photon-Counting Detector CT.

BACKGROUND. The higher spatial resolution and image contrast for iodine-containing tissues of photon-counting detector (PCD) CT may address challenges in evaluating small calcified vessels when performing lower extremity CTA by energy-integrating detector (EID) CTA. OBJECTIVE. The purpose of the study was to compare the evaluation of infrapopliteal vasculature between lower extremity CTA performed using EID CT and PCD CT. METHODS. This prospective study included 32 patients (mean age, 69.7 ± 11.3 [SD] years; 27 men, five women) who underwent clinically indicated lower extremity EID CTA between April 2021 and March 2022; participants underwent investigational lower extremity PCD CTA later the same day as EID CTA using a reduced IV contrast media dose. Two radiologists independently reviewed examinations in two sessions, each containing a random combination of EID CTA and PCD CTA examinations; the readers assessed the number of visualized fibular perforators, characteristics of stenoses at 11 infrapopliteal segmental levels, and subjective arterial sharpness. RESULTS. Mean IV contrast media dose was 60.0 ± 11.0 (SD) mL for PCD CTA versus 139.6 ± 11.8 mL for EID CTA (p < .001). The number of identified fibular perforators per lower extremity was significantly higher for PCD CTA than for EID CTA for reader 1 (R1) (mean ± SD, 6.4 ± 3.2 vs 4.2 ± 2.4; p < .001) and reader 2 (R2) (8.8 ± 3.4 vs 7.6 ± 3.3; p = .04). Reader confidence for assessing stenosis was significantly higher for PCD CTA than for EID CTA for R1 (mean ± SD, 82.3 ± 20.3 vs 78.0 ± 20.2; p < .001) but not R2 (89.8 ± 16.7 vs 90.6 ± 7.1; p = .24). The number of segments per lower extremity with total occlusion was significantly lower for PCD CTA than for EID CTA for R2 (mean ± SD, 0.5 ± 1.3 vs 0.9 ± 1.7; p = .04) but not R1 (0.6 ± 1.3 vs 1.0 ± 1.5; p = .07). The number of segments per lower extremity with clinically significant nonocclusive stenosis was significantly higher for PCD CTA than for EID CTA for R1 (mean ± SD, 2.2 ± 2.2 vs 1.6 ± 1.7; p = .01) but not R2 (1.1 ± 2.0 vs 1.1 ± 1.4; p = .89). Arterial sharpness was significantly greater for PCD CTA than for EID CTA for R1 (mean ± SD, 3.2 ± 0.5 vs 1.8 ± 0.5; p < .001) and R2 (3.2 ± 0.4 vs 1.7 ± 0.8; p < .001). CONCLUSION. PCD CTA yielded multiple advantages relative to EID CTA for visualizing small infrapopliteal vessels and characterizing associated plaque. CLINICAL IMPACT. The use of PCD CTA may improve vascular evaluation in patients with peripheral arterial disease.

Improved Pulmonary Artery Evaluation Using High-Pitch Photon-Counting CT Compared to High-Pitch Conventional or Routine-Pitch Conventional Dual-Energy CT.

OBJECTIVE: Pulmonary CT angiography (CTA) to detect pulmonary emboli can be performed using conventional dual-source CT with single-energy acquisition at high-pitch (high-pitch conventional CT), which minimizes motion artifacts, or routine-pitch, dual-energy acquisitions (routine-pitch conventional DECT), which maximize iodine signal. We compared iodine signal, radiation dose, and motion artifacts of pulmonary CTA between these conventional CT modalities and dual-source photon-counting detector CT with high-pitch, multienergy acquisitions (high-pitch photon-counting CT). METHODS: Consecutive clinically indicated pulmonary CTA exams were collected. CT number/noise was measured from the main to right lower lobe segmental pulmonary arteries using 120 kV threshold low, 120 kV, and mixed kV (0.6 linear blend) images. Three radiologists reviewed anonymized, randomized exams, rating them using a 4- or 5-point Likert scale (1 = worst, and 4/5 = best) for contrast enhancement in pulmonary arteries, motion artifacts in aortic root to subsegmental pulmonary arteries, lung image quality; pulmonary blood volume (PBV) map image quality (for multienergy or dual-energy exams), and contribution to reader confidence. RESULTS: One hundred fifty patients underwent high-pitch photon-counting CT (n = 50), high-pitch conventional CT (n = 50), and routine-pitch conventional DECT (n = 50). High-pitch photon-counting CT had lower radiation dose (CTDIvol: 8.1 ± 2.5 vs 9.6 ± 6.8 and 16.2 ± 8.5 mGy, respectively; P < 0.001), and routine-pitch conventional DECT had significantly less contrast (P < 0.009). CT number and CNR measurements were significantly greater at high-pitch photon-counting CT (P < 0.001). Across readers, high-pitch photon-counting CT demonstrated significantly higher subjective contrast enhancement in the pulmonary arteries compared to the other modalities (4.7 ± 0.6 vs 4.4 ± 0.7 vs 4.3 ± 0.7; P = 0.011) and lung image quality (3.4 ± 0.5 vs 3.1 ± 0.5 vs 3.1 ± 0.5; P = 0.013). High-pitch photon-counting CT and high-pitch conventional CT had fewer motion artifacts at all levels compared to DECT (P < 0.001). High-pitch photon-counting CT PBV maps had superior image quality (P < 0.001) and contribution to reader confidence (P < 0.001) compared to routine-pitch conventional DECT. CONCLUSION: High-pitch photon-counting pulmonary CTA demonstrated higher contrast in pulmonary arteries at lower radiation doses with improved lung image quality and fewer motion artifacts compared to high-pitch conventional CT and routine-pitch conventional dual-energy CT.

Obtaining assent for research involving children in Malaysia: a position statement from the Academy of Medicine of Malaysia College of Paediatrics.

The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.

Using Dynamic Oral Dosing of Rifapentine and Rifabutin to Simulate Exposure Profiles of Long-Acting Formulations in a Mouse Model of Tuberculosis Preventive Therapy.

Administration of tuberculosis preventive therapy (TPT) to individuals with latent tuberculosis infection is an important facet of global tuberculosis control. The use of long-acting injectable (LAI) drug formulations may simplify and shorten regimens for this indication. Rifapentine and rifabutin have antituberculosis activity and physiochemical properties suitable for LAI formulation, but there are limited data available for determining the target exposure profiles required for efficacy in TPT regimens. The objective of this study was to determine exposure-activity profiles of rifapentine and rifabutin to inform development of LAI formulations for TPT. We used a validated paucibacillary mouse model of TPT in combination with dynamic oral dosing of both drugs to simulate and understand exposure-activity relationships to inform posology for future LAI formulations. This work identified several LAI-like exposure profiles of rifapentine and rifabutin that, if achieved by LAI formulations, could be efficacious as TPT regimens and thus can serve as experimentally determined targets for novel LAI formulations of these drugs. We present novel methodology to understand the exposure-response relationship and inform the value proposition for investment in development of LAI formulations that have utility beyond latent tuberculosis infection.

Different prognostic role of EGFR mutation according to the IASLC histological grade in patients with resected early-stage lung adenocarcinoma.

AIMS: The prognostic role of EGFR mutations remains controversial. We aimed to evaluate the prognostic role of EGFR mutation in consideration of the IASLC histological grade in patients with resected early-stage lung adenocarcinoma. METHODS AND RESULTS: A total of 3297 patients with stages I-IIA resected lung adenocarcinoma who had had EGFR mutation tests between January 2014 and December 2019 at the Samsung Medical Center, Seoul, Korea were included. Recurrence-free survival (RFS) was compared by EGFR mutation status (EGFR-M+ versus EGFR-WT) and IASLC histological grade (G1, G2 and G3). Cox proportional hazards models were used to estimate the adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS: Compared to the EGFR-WT group, the EGFR-M+ group had a significantly lower proportion of G3 tumour (16 versus 33%, P < 0.001). During a median follow-up of 41.4 months, 376 patients experienced recurrence. After adjusting for histological grade, the aHR for recurrence comparing the EGFR-M+ to the EGFR-WT was 1.30 (95% CI = 1.04-1.62, P = 0.022). The EGFR-M+ group had a significantly lower 5-year RFS than the EGFR-WT group among G3 patients (58.4 versus 71.5%, P < 0.001), but not among G1 and G2 patients. CONCLUSIONS: EGFR mutation status was associated with a risk of recurrence after consideration of the IASLC histological grading, especially in G3 tumours. The results of this study would be useful for developing a new staging system and identifying a subset of patients who may benefit from adjuvant targeted therapy.

Durable Response in Patients With Refractory Fistulizing Perianal Crohn's Disease Using Autologous Mesenchymal Stem Cells on a Dissolvable Matrix: Results from the Phase I Stem Cell on Matrix Plug Trial.

BACKGROUND: Refractory perianal Crohn's disease remains notoriously difficult to treat. We developed a novel technology using a commercially available bioabsorbable fistula plug to deliver autologous adipose-derived mesenchymal stem cells. OBJECTIVE: This study aimed to assess therapeutic safety and feasibility in the completed STOMP (stem cells on matrix plugs) phase 1 clinical trial. DESIGN: Prospective single-arm phase I clinical trial. SETTING: Tertiary academic medical center. PATIENTS: Adults (aged 18-65 y) with complex single-tract Crohn's disease perianal fistula who have failed conventional therapy were included in this study. INTERVENTION: Autologous adipose-derived mesenchymal stem cells were isolated, ex vivo culture expanded, and seeded onto a commercially available bioabsorbable fistula plug. Six weeks later, patients returned to the operating room for removal of the seton and placement of the stem cell-loaded plug. MAIN OUTCOME MEASURES: Patients were followed up for a total of 8 visits through 12 months. Safety was the primary end point; clinical healing and MRI response were secondary end points. RESULTS: Twenty patients (12 females; mean age 36 y) were treated with the stem cell-loaded plug. Of the 20 patients enrolled, 3 were not included in the 12-month analysis because of study withdrawal. Through 12 months, no patient experienced a serious adverse event related to the stem cell-loaded plug. Four patients experienced 7 serious adverse events and 12 patients experienced 22 adverse events. Complete clinical healing occurred in 14 of 18 patients at 6 months and 13 of 17 patients at 12 months. MRI response was observed in 12 of 18 patients at 6 months. LIMITATIONS: The main limitations were the small sample size and restrictive inclusion criteria. CONCLUSIONS: A stem cell-loaded plug can safely and effectively deliver cell-based therapy for patients with single-tract fistulizing perianal Crohn's disease. See Video Abstract at http://links.lww.com/DCR/C70 . RESPUESTA DURADERA OBSERVADA EN PACIENTES CON ENFERMEDAD DE CROHN PERIANAL FISTULIZANTE REFRACTARIA MEDIANTE EL USO DE CLULAS MADRE MESENQUIMALES AUTLOGAS EN UNA MATRIZ DISOLUBLE RESULTADOS DEL ENSAYO DE FASE I STEM CELL ON MATRIX PLUG: ANTECEDENTES:La enfermedad de Crohn perianal refractaria sigue siendo notoriamente difícil de tratar. Desarrollamos una tecnología novedosa utilizando un tapón de fístula bioabsorbible disponible comercialmente para administrar células madre mesenquimales derivadas de tejido adiposo autólogo.OBJETIVO:Evaluar la seguridad y viabilidad terapéutica en el ensayo finalizado STOMP.DISEÑO:Ensayo clínico prospectivo de fase I de un solo brazo.AJUSTE:Centro médico académico terciario.PACIENTES:Adultos (18-65) con fístula perianal compleja de la enfermedad de Crohn de un solo tracto que han fracasado con la terapia convencional.INTERVENCIÓN:Se aislaron células madre mesenquimales derivadas de tejido adiposo autólogo, se expandieron en cultivo ex vivo y se sembraron en un tapón de fístula bioabsorbible disponible comercialmente. Seis semanas después, los pacientes regresaron al quirófano para retirar el setón y colocar el tapón cargado de células madre.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes fueron seguidos durante un total de 8 visitas durante 12 meses. La seguridad fue el criterio principal de valoración; la curación clínica y la respuesta a la resonancia magnética fueron criterios de valoración secundarios.RESULTADOS:Veinte pacientes (12 mujeres, edad media 36 años) fueron tratados con el tapón cargado de células madre. De los 20 pacientes inscritos, tres no se incluyeron en el análisis de 12 meses porque se retiraron del estudio. A lo largo de 12 meses, ningún paciente experimentó un evento adverso grave relacionado con el tapón cargado de células madre. Cuatro pacientes experimentaron 7 eventos adversos graves y 12 pacientes experimentaron 22 eventos adversos. La curación clínica completa ocurrió en 14 de 18 pacientes a los 6 meses y en 13 de 17 pacientes a los 12 meses. La respuesta a la resonancia magnética se observó en 12 de 18 pacientes a los 6 meses.LIMITACIONES:Las principales limitaciones son el tamaño pequeño de la muestra y los criterios de inclusión restrictivos.CONCLUSIONES:Un tapón cargado de células madre se puede administrar de manera segura y efectiva, una terapia basada en células para pacientes con enfermedad de Crohn perianal fistulizante de un solo tracto. Consule Video Resumen en http://links.lww.com/DCR/C70 . (Traducción- Dr. Yesenia Rojas-Khalil ).

Diagnostic Performance in Low- and High-Contrast Tasks of an Image-Based Denoising Algorithm Applied to Radiation Dose-Reduced Multiphase Abdominal CT Examinations.

BACKGROUND. Anatomic redundancy between phases can be used to achieve denoising of multiphase CT examinations. A limitation of iterative reconstruction (IR) techniques is that they generally require use of CT projection data. A frequency-split multi-band-filtration algorithm applies denoising to the multiphase CT images themselves. This method does not require knowledge of the acquisition process or integration into the reconstruction system of the scanner, and it can be implemented as a supplement to commercially available IR algorithms. OBJECTIVE. The purpose of the present study is to compare radiologists' performance for low-contrast and high-contrast diagnostic tasks (i.e., tasks for which differences in CT attenuation between the imaging target and its anatomic background are subtle or large, respectively) evaluated on multiphase abdominal CT between routine-dose images and radiation dose-reduced images processed by a frequency-split multiband-filtration denoising algorithm. METHODS. This retrospective single-center study included 47 patients who underwent multiphase contrast-enhanced CT for known or suspected liver metastases (a low-contrast task) and 45 patients who underwent multiphase contrast-enhanced CT for pancreatic cancer staging (a high-contrast task). Radiation dose-reduced images corresponding to dose reduction of 50% or more were created using a validated noise insertion technique and then underwent denoising using the frequency-split multi-band-filtration algorithm. Images were independently evaluated in multiple sessions by different groups of abdominal radiologists for each task (three readers in the low-contrast arm and four readers in the high-contrast arm). The noninferiority of denoised radiation dose-reduced images to routine-dose images was assessed using the jackknife alternative free-response ROC (JAFROC) figure-of-merit (FOM; limit of noninferiority, -0.10) for liver metastases detection and using the Cohen kappa statistic and reader confidence scores (100-point scale) for pancreatic cancer vascular invasion. RESULTS. For liver metastases detection, the JAFROC FOM for denoised radiation dose-reduced images was 0.644 (95% CI, 0.510-0.778), and that for routine-dose images was 0.668 (95% CI, 0.543-0.792; estimated difference, -0.024 [95% CI, -0.084 to 0.037]). Intraobserver agreement for pancreatic cancer vascular invasion was substantial to near perfect when the two image sets were compared (κ = 0.53-1.00); the 95% CIs of all differences in confidence scores between image sets contained zero. CONCLUSION. Multiphase contrast-enhanced abdominal CT images with a radiation dose reduction of 50% or greater that undergo denoising by a frequency-split multiband-filtration algorithm yield performance similar to that of routine-dose images for detection of liver metastases and vascular staging of pancreatic cancer. CLINICAL IMPACT. The image-based denoising algorithm facilitates radiation dose reduction of multiphase examinations for both low- and high-contrast diagnostic tasks without requiring manufacturer-specific hardware or software.

Impact of dual-energy 50-keV virtual monoenergetic images on radiologist confidence in detection of key imaging findings of small hepatocellular carcinomas using multiphase liver CT.

BACKGROUND: Dual-energy virtual monoenergetic images can increase iodine signal, potentially increasing the conspicuity of hepatic masses. PURPOSE: To determine if dual-energy 50-keV virtual monoenergetic images improve visualization of key imaging findings or diagnostic confidence for small (≤2 cm) hepatocellular carcinomas (HCC) at multiphase, contrast-enhanced liver computed tomography (CT). MATERIAL AND METHODS: Patients with chronic liver disease underwent multiphase dual-energy CT imaging for HCC, with late arterial and delayed phase dual-energy 50-keV images reconstructed. Two non-reader subspecialized gastrointestinal (GI) radiologists established the reference standard, determining the location and diagnosis of all hepatic lesions using predetermined criteria. Three GI radiologists interpreted mixed kV CT images without or with dual-energy 50-keV images. Radiologists identified potential HCCs and rated their confidence (0-100 scales) in imaging findings of arterial enhancement, enhancing capsule, tumor washout, and LI-RADS 5 (2018) category. RESULTS: In total, 45 patients (14 women; mean age = 59.5 ± 10.9 years) with chronic liver disease were included. Of them, 19 patients had 25 HCCs ≤2 cm (mean size = 1.5 ± 0.4 cm). There were 17 LI-RADS 3 and 4 lesions and 19 benign lesions. Reader confidence in imaging findings of arterial enhancement, enhancing capsule, and non-peripheral washout significantly increased with dual-energy images (P ≤ 0.022). Overall confidence in HCC diagnosis increased significantly with dual-energy 50-keV images (52.4 vs. 68.8; P = 0.001). Dual-energy images demonstrated a slight but significant decrease in overall image quality. CONCLUSION: Radiologist confidence in key imaging features of small HCCs and confidence in imaging diagnosis increases with use of dual-energy 50-keV images at multiphase, contrast-enhanced liver CT.

Outcomes of patients with exomphalos and associated congenital heart diseases.

INTRODUCTION: Exomphalos is an anterior abdominal wall defect resulting in herniation of contents into the umbilical cord. Severe associated chromosomal anomalies and congenital heart disease (CHD) are known to influence mortality, but it is not clear which cardiac anomalies have the greatest impact on survival. METHODS: We performed a retrospective review of the treatment and outcome of patients with exomphalos over a 30-year period (1990-2020), with a focus on those with the combination of exomphalos major and major CHD (EMCHD). RESULTS: There were 123 patients with exomphalos identified, 59 (48%) had exomphalos major (ExoMaj) (defect > 5 cm or containing liver), and 64 (52%) exomphalos minor (ExoMin). In the ExoMaj group; 17% had major CHD (10/59), M:F 28:31, 29% premature (< 37 weeks, 17/59) and 14% had low birth-weight (< 2.5 kg, 8/59). In the ExoMin group; 9% had major CHD (6/64), M:F 42:22, 18% premature and 10% had low birth-weight. The 5-year survival was 20% in the EMCHD group versus 90% in the ExoMaj with minor or no CHD [p < 0.0001]. Deaths in the EMCHD had mainly right heart anomalies and all of them required mechanical ventilation (MV) for pulmonary hypoplasia prior to cardiac intervention. In contrast, survivors did not require mechanical ventilation prior to cardiac intervention. CONCLUSION: EMCHD is associated with high mortality. The most significant finding was high mortality in those with right heart anomalies in combination with pulmonary hypoplasia, especially if pre-intervention mechanical ventilation is required.

Tumor immune microenvironment of primary colorectal adenocarcinomas metastasizing to the liver or lungs.

BACKGROUND: Because of the heterogeneity of metastatic colorectal cancer (mCRC), a genome-wide analysis was performed to characterize the tumor immune microenvironment (TIME). METHODS: RNA-seq analysis of 62 primary CRCs without and 63 with systemic metastasis (SM- and SM+ groups) was conducted, and the data were used in a training set after adjustment by propensity score matching. Samples were further subdivided into those with hepatic metastasis (CHM subgroup), pulmonary metastasis (CPM subgroup), or concurrent CHM and CPM (concurrent group). Validation was done by quantitative reverse-transcription polymerase chain reaction using another 40 primary CRC samples. RESULTS: Compared with the CHM or CPM subgroups, the concurrent group showed upregulated in inflammatory or immune processes, cytokine secretion, and myeloid leukocyte migration. Nine candidate genes were selected: SM-specific IDO1, JAM3, and PDE2A; CHM- or CPM-specific BIRC7; CPM-specific HISI1H2BK, and both SM-specific and CHM- or CPM-specific EPHB6, LPL, THBD, and PPBP. In a validation set of primary CRCs, JAM3 and IDO1 (p = 0.044 and p = 0.036, respectively) were confirmed to show significant upregulation and downregulation, respectively, in the SM+ group, whereas HIST1H2BK (p = 0.017) was significantly upregulated in the CPM subgroup. CONCLUSIONS: Our findings indicate that a host-suppressive TIME is established in the primary tumor of mCRC and identify immune-related site-specific markers of mCRC.

Caregiving, care burden and awareness of caregivers and patients with dementia in Asian locations: a secondary analysis.

BACKGROUND: This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer's disease (AD) across different Asian locations. METHODS: This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients' awareness of their dementia diagnosis was assessed by asking the following yes/no question: "Do you have dementia?" Caregivers' awareness of the patient's dementia diagnosis was assessed by asking the following yes/no question: "Does your patient have dementia?" RESULTS: In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p < 0.001 and p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p < 0.001). CONCLUSIONS: Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02262975 . Registered 13 October 2014.

The feasibility of low iodine dynamic CT angiography with test bolus for evaluation of lower extremity peripheral artery disease.

OBJECTIVE: This study aims to determine if low iodine dynamic computed tomography angiography performed after a fixed delay or test bolus acquisition demonstrates high concordance with clinical computed tomography angiography (using a routine amount of iodinated contrast) to display lower extremity peripheral arterial disease. METHODS: After informed consent, low iodine dynamic computed tomography angiography examination (using either a fixed delay or test bolus) using 50 ml of iodine contrast media was performed. A subsequent clinical computed tomography angiography using standard iodine dose (115 or 145 ml) served as the reference standard. A vascular radiologist reviewed dynamic and clinical computed tomography angiography images to categorize the lumen into "not opacified", "<50% stenosis", " 50 ̶70% stenosis", ">70% stenosis", and "occluded" for seven arterial segments in each lower extremity. Concordance between low iodine dynamic computed tomography angiography and the routine iodine reference standard was calculated. The clinical utility of 4D volume-rendered images was also evaluated. RESULTS: Sixty-eight patients (average age 66.1 ± 12.3 years, male; female = 49: 19) were enrolled, with 34 patients each undergoing low iodine dynamic computed tomography angiography using fixed delay and test bolus techniques, respectively. One patient assigned to the test bolus group did not undergo low iodine computed tomography angiography due to unavailable delayed time. The fixed delay was 13 s, with test bolus acquisition resulting in a mean variable delay prior to image acquisition of 19.5 s (range; 8-32 s). Run-off to the ankle was observed using low iodine dynamic computed tomography angiography following fixed delay and test bolus acquisition in 76.4% (26/34) and 100% (33/33) of patients, respectively (p = 0.005). Considering extremities with run-off to the ankle and without severe artifact, the concordance rate between low iodine dynamic computed tomography angiography and the routine iodine reference standard was 86.8% (310/357) using fixed delay and 97.9% (425/434) using test bolus (p < 0.001). 4D volume-rendered images using fixed delay and test bolus demonstrated asymmetric flow in 57.7% (15/26) and 58.1% (18/31) (p = 0.978) of patients, and collateral blood flow in 11.5% (3/26) and 22.6% (7/31) of patients (p = 0.319), respectively. CONCLUSION: Low iodine dynamic computed tomography angiography with test bolus acquisition has a high concordance with routine peripheral computed tomography angiography performed with standard iodine dose, resulting in improved run-off to the ankle compared to dynamic computed tomography angiography performed after a fixed delay. This method is useful for minimizing iodine dose in patients at risk for contrast-induced nephropathy. 4D volume-rendered computed tomography angiography images provide useful dynamic information.

Transapical access for dilatation of a Melody valve in the mitral position using large balloons, in a small child: a case description with midterm follow-up and literature review.

The surgical placement of the Melody®valve in the mitral position in infants and young children was first reported in 2012. Since then, there have only been a limited number of technically oriented reports describing catheter techniques to tackle valve-related issues such as valve adjustment for somatic growth or the management of haemodynamically significant paravalvar regurgitation. We present a case study where severe paravalvar leaks were tackled using a hybrid approach and large low-pressure balloons in a child who had previously undergone Melody® valve implantation in the mitral position. The technical outcome remains very good at 18 months follow-up and the patient remains symptom-free.

Giant epithelial nonparasitic splenic cyst a pre-operative diagnosis dilemma: A case report.

Giant splenic cyst is rare disorder affecting the spleen. As the occurrence is so in-frequent that the diagnosis preoperatively remains a challenge. We report a 12-year-old boy who presented to Sarawak General Hospital, Malaysia with left upper abdominal pain initially mistaken as a complex left liver cyst. He underwent surgery which turned out to be a giant splenic cyst and underwent laparotomy and total splenectomy. He was discharged well and remains asymptomatic after 6 months postoperative follow up.

Lanthanide-Binding Tags for 3D X-ray Imaging of Proteins in Cells at Nanoscale Resolution.

We report the application of lanthanide-binding tags (LBTs) for two- and three-dimensional X-ray imaging of individual proteins in cells with a sub-15 nm beam. The method combines encoded LBTs, which are tags of minimal size (ca. 15-20 amino acids) affording high-affinity lanthanide ion binding, and X-ray fluorescence microscopy (XFM). This approach enables visualization of LBT-tagged proteins while simultaneously measuring the elemental distribution in cells at a spatial resolution necessary for visualizing cell membranes and eukaryotic subcellular organelles.

Preserved Efficacy and Reduced Toxicity with Intermittent Linezolid Dosing in Combination with Bedaquiline and Pretomanid in a Murine Tuberculosis Model.

The novel regimen of bedaquiline, pretomanid, and linezolid (BPaL) is highly effective against drug-resistant tuberculosis, but linezolid toxicities are frequent. We hypothesized that, for a similar total weekly cumulative dose, thrice-weekly administration of linezolid would preserve efficacy while reducing toxicity compared with daily dosing, in the context of the BPaL regimen. Using C3HeB/FeJ and BALB/c mouse models of tuberculosis disease, thrice-weekly linezolid dosing was compared with daily dosing, with intermittent dosing introduced (i) from treatment initiation or (ii) after an initial period of daily dosing. In all animals, BPa was dosed daily throughout treatment. Blood counts were used to assess hematologic toxicity. After unexpected findings of apparent antagonism, we conducted additional experiments to investigate strain-to-strain differences in the contribution of linezolid to regimen efficacy by comparing each 1- and 2-drug component to the BPaL regimen in BALB/c mice infected with Mycobacterium tuberculosis H37Rv or HN878. Giving linezolid daily for 1 to 2 months achieved the greatest efficacy but, after that, results were similar if the drug was stopped, dosed thrice-weekly, or continued daily. Erythrocyte counts were lower with daily than thrice-weekly dosing. Linezolid had additive effects with BPa against M. tuberculosis H37Rv but antagonistic effects with BPa against M. tuberculosis HN878. However, the overall efficacy of BPaL was high and similar against both strains. Dosing linezolid daily for the first 2 months and then less frequently thereafter may optimize its therapeutic margin. Linezolid's contribution to BPaL regimens may depend on the M. tuberculosis strain.

2D MEMS-based multilayer Laue lens nanofocusing optics for high-resolution hard x-ray microscopy.

We report on the development of 2D integrated multilayer Laue lens (MLL) nanofocusing optics used for high-resolution x-ray microscopy. A Micro-Electro-Mechanical-Systems (MEMS) - based template has been designed and fabricated to accommodate two linear MLL optics in pre-aligned configuration. The orthogonality requirement between two MLLs has been satisfied to a better than 6 millidegrees level, and the separation along the x-ray beam direction was controlled on a micrometer scale. Developed planar 2D MLL structure has demonstrated astigmatism free point focus of ∼14 nm by ∼13 nm in horizontal and vertical directions, respectively, at 13.6 keV photon energy. Approaching 10 nm resolution with integrated 2D MLL optic is a significant step forward in applications of multilayer Laue lenses for high-resolution hard x-ray microscopy and their adoption by the general x-ray microscopy community.

The relationship among flow index, uroflowmetry curve shape, and EMG lag time in children.

PURPOSE: To determine the relationship among flow index (FI), uroflowmetry curve shape, and electromyography (EMG) lag time in children. MATERIALS AND METHODS: A total of 294 children with lower urinary tract symptoms were included. The overall relationship between lag time and FI was investigated with curve estimation regression. Normal and primary bladder neck dysfunction was defined according to the previous classification, while patients with a lag time less than 2 seconds were grouped based on 2-second intervals. We also categorized cases into four groups (tower shaped, bell shaped, plateau shaped, and fractionated void) by FI and compared lag time. RESULTS: The overall distribution chart demonstrated that FI was the highest at lag time 0 second and decreased with the change in lag time both ways. The best fitting model for maximum FI and lag time was a cubic model (R2 = .282; P < .001). Children with lag times from 0 to less than 2 seconds showed the highest mean FI, while those with prolonged (>6 seconds) or delayed lag time (<-4 seconds) demonstrated lower mean FI values. EMG lag time of the tower-shaped curve was significantly close to 0 second, and plateau shaped and fractionated void had either prolonged or delayed. CONCLUSIONS: A lag time close to 0 second was associated with higher FI, representing hyperefficient voiding with a tower-shaped flow pattern. However, children with prolonged or delayed lag time showed a lower FI, implicating hypoefficient voiding and a plateau-shaped flow pattern. The relationship between FI and EMG lag time could be a cornerstone for a comprehensive understanding of voiding status.