T2-fluid attenuated inversion recovery mismatch in tumefactive multiple sclerosis.

The T2-fluid attenuated inversion recovery (FLAIR) mismatch sign has been suggested as an imaging marker of isocitrate dehydrogenase-mutant 1p/19q non-codeleted gliomas with 100% specificity. Tumefactive demyelination is a common mimic of neoplasm that has led to unnecessary biopsies and even resections. We report a case of tumefactive multiple sclerosis in a 46-year-old male without prior symptomatic demyelinating episodes that demonstrates the T2-FLAIR mismatch sign. Our findings suggest the T2-FLAIR mismatch sign should not be used as a differential feature between glioma and tumefactive demyelination. Because typical isocitrate dehydrogenase-mutant 1p/19q non-codeleted gliomas typically do not demonstrate significant enhancement, such diagnosis should be reserved when post-contrast images are unavailable.

Characteristics and Outcomes of Lung Cancers Detected on Low-Dose Lung Cancer Screening CT.

BACKGROUND: Lung cancer screening (LCS) with low-dose CT (LDCT) was implemented in the United States following the National Lung Screening Trial (NLST). The real-world benefits of implementing LCS are yet to be determined with outcome-oriented data. The study objective is to investigate the characteristics and outcomes of screening-detected lung cancers. METHODS: This single-institution retrospective study included LCS patients between June 2014 and December 2019. Patient demographics, number of screening rounds, imaging features, clinical workup, disease extent, histopathology, treatment, complications, and mortality outcomes of screening-detected lung cancers were extracted and compared with NLST data. RESULTS: LCS LDCTs (7,480) were performed on 4,176 patients. The cancer detection rate was 3.8%, higher than reported by NLST (2.4%, P < 0.0001), and cancers were most often found in patients ≥65 years (62%), older than those in NLST (41%, P < 0.0001). The patients' ethnicity was similar to NLST, P = 0.87. Most LCS-detected cancers were early stage I tumors (71% vs. 54% in NLST, P < 0.0001). Two thirds of cancers were detected in the first round of screening (67.1%) and were multifocal lung cancers in 15%. As in NLST, the complication rate after invasive workup or surgery was low (24% vs. 28% in NLST, P = 0.32). Over a median follow-up of 3.3 years, the mortality rate was 0.45%, lower than NLST (1.33%, P < 0.0001). CONCLUSIONS: LCS implementation achieved a higher cancer detection rate, detection of early-stage cancers, and more multifocal lung cancers compared with the NLST, with low complications and mortality. IMPACT: The real-world implementation of LCS has been successful for detection of lung cancer with favorable outcomes.

Imaging Considerations in Spinal Cord Evaluation.

Multiple diverse pathologies result in the clinical presentation of myelopathy. The preferred way to image the spinal cord depends on clinical history, anatomic site of interest, and patient issues limiting certain imaging modalities. This radiology-focused article discusses pertinent physiological considerations, reviews basic and newer imaging techniques, and examines several distinct disease entities in order to highlight the key role of imaging in the work-up of myelopathy.

Clinical and Imaging Features of Non-Small-Cell Lung Cancer in Young Patients.

BACKGROUND: Non-small-cell lung cancer (NSCLC) in young adult patients is rare, with scarce data available in patients aged < 40 years and even less in those aged < 35 years. Our goal was to determine the presenting symptoms, clinicopathologic characteristics, and imaging features of young patients with NSCLC at time of diagnosis and compare them to those of older adults. PATIENTS AND METHODS: We retrospectively analyzed the medical records and imaging of young patients (≤ 40 years old) with NSCLC treated at our institution between 1998 and 2018. Patients < 35 years old were compared to those between 35 and 40 years old. Characteristics of patients ≤ 40 years old were compared to older patients (> 40 years) from publicly available data sets. RESULTS: We identified 166 young patients with NSCLC (median age, 36.6 years; range, 18-40 years). Most presented with nonspecific respiratory symptoms and were diagnosed with pneumonia (84/136, 62%). Compared to patients < 35 years old, patients 35-40 years old were more likely to have malignancy detected incidentally (15% vs. 5%, P = .04). Patients < 35 years old were more likely to have central tumors (55% vs. 33%, P = .02) and to have bone (38% vs. 19%, P = .007) and lung (39% vs. 24%, P = .03) metastases. Compared to older patients (> 40 years), young patients were more likely to be never smokers (65.0% vs. 14.7%, P < .001) and to have advanced disease (88% vs. 66%, P < .001). CONCLUSION: Young patients with NSCLC often present with nonspecific symptoms and have advanced disease at diagnosis, often mimicking other pathologies. Awareness of the clinical presentation and imaging features of NSCLC in young patients may help minimize delays in diagnoses.

Perinatal maternal undernutrition does not result in offspring capillary rarefaction in the middle-aged male baboon at rest.

Microvascular health is a main determinant of coronary blood flow reserve and myocardial vascular resistance. Extracardiac capillary abnormality has been reported in subjects at increased coronary heart disease risk, such as prehypertension, hypertension, diabetes, hyperlipidemia, and atherosclerosis. We have reported cardiovascular dysfunction in a cohort of maternal nutrient reduction (MNR)-induced intrauterine growth restriction (IUGR) baboon offspring. Here we test the hypothesis that there is oral capillary rarefaction associated with MNR-induced IUGR. Capillary density was quantified using in vivo high-power capillaroscopy on seven middle-aged (~10.7 yr; human equivalent ~40 yr) male IUGR baboons and seven male age-matched controls in the lateral buccal and inferior labial mucosa. While no difference was found between groups in either area by fraction area or optical density for these vascular beds derived from fetal preductal vessels, further studies are needed on post-ductal vascular beds, retina, and function.

The nonhuman primate hypothalamo-pituitary-adrenal axis is an orchestrator of programming-aging interactions: role of nutrition.

Developmental programming alters life-course multi-organ function and significantly affects life-course health. Recently, interest has developed in how programming may influence the rate of aging. This review describes interactions of nutrition and programming-aging interactions in hypothalamo-pituitary-adrenal (HPA) development and function from fetal development to old age. A full picture of these interactions requires data on levels of HPA activity relating to the hypothalamic, adrenal cortical, circulating blood, and peripheral cortisol metabolism. Data are provided from studies on our baboon, nonhuman primate model both across the normal life course and in offspring of maternal baboons who were moderately undernourished by a global 30% diet reduction during pregnancy and lactation. Sex differences in offspring outcomes in response to similar challenges are described. The data clearly show programming of increased HPA axis activity by moderate maternal undernutrition. Increased postnatal circulating cortisol concentrations are related to accelerated aging of the brain and cardiovascular systems. Future studies should address peripheral cortisol production and the influence of aging advantage in females. These data support the view that the HPA is an orchestrator of interactions of programming-aging mechanisms.

Target-specific yield rate and clinical utility of percutaneous tissue sampling in spinal infection.

BACKGROUND: Percutaneous tissue sampling in spondylodiscitis is frequently performed but with highly variable yield in literature and unclear clinical impact. Factors that influence the culture success rate are not well established. OBJECTIVE: To determine target specific yield and clinical impact of percutaneous biopsy in clinically and imaging diagnosed spinal infection and factors that may influence the yield rate. METHODS: Institutional review board approved single center retrospective chart review from 2015 to 2019 analyzing imaging findings, clinical notes, procedural reports, and laboratory results on cases of concurrent imaging and clinically diagnosed spondylodiscitis that underwent percutaneous tissue sampling. RESULTS: A total of 111 patients and 189 specimens were analyzed. The overall culture yield in spondylodiscitis was approximately 27%, 9% affecting management. Abscess/fluid and septic arthritis aspirations had higher yield rates compared to soft tissue/phlegmon aspirations. Core sampling of the bone and disc yielded positive culture 12% of the time, 2% resulted in change in management. Upper thoracic spine biopsies were more frequently positive and associated with change in management. Positive culture elsewhere in the body represented the major reason underlying lack of clinical impact. Lack of prior antibiotic treatment and diabetes mellitus demonstrated a trend toward higher culture positivity, although a larger sample size is needed to confirm these findings. No repeat biopsy yielded positive culture. Staphylococcus spp. accounted for approximately half of the microorganisms cultured. In positive biopsies where infection was also found elsewhere in the body, the organism was nearly always congruent (96%).

Clinical and imaging features predict mortality in COVID-19 infection in Iran.

The new coronavirus disease 2019 (COVID-19) pandemic has challenged many healthcare systems around the world. While most of the current understanding of the clinical features of COVID-19 is derived from Chinese studies, there is a relative paucity of reports from the remaining global health community. In this study, we analyze the clinical and radiologic factors that correlate with mortality odds in COVID-19 positive patients from a tertiary care center in Tehran, Iran. A retrospective cohort study of 90 patients with reverse transcriptase-polymerase chain reaction (RT-PCR) positive COVID-19 infection was conducted, analyzing demographics, co-morbidities, presenting symptoms, vital signs, laboratory values, chest radiograph findings, and chest CT features based on mortality. Chest radiograph was assessed using the Radiographic Assessment of Lung Edema (RALE) scoring system. Chest CTs were assessed according to the opacification pattern, distribution, and standardized severity score. Initial and follow-up Chest CTs were compared if available. Multiple logistic regression was used to generate a prediction model for mortality. The 90 patients included 59 men and 31 women (59.4 ± 16.6 years), including 21 deceased and 69 surviving patients. Among clinical features, advanced age (p = 0.02), low oxygenation saturation (p<0.001), leukocytosis (p = 0.02), low lymphocyte fraction (p = 0.03), and low platelet count (p = 0.048) were associated with increased mortality. High RALE score on initial chest radiograph (p = 0.002), presence of pleural effusions on initial CT chest (p = 0.005), development of pleural effusions on follow-up CT chest (p = 0.04), and worsening lung severity score on follow-up CT Chest (p = 0.03) were associated with mortality. A two-factor logistic model using patient age and oxygen saturation was created, which demonstrates 89% accuracy and area under the ROC curve of 0.86 (p<0.0001). Specific demographic, clinical, and imaging features are associated with increased mortality in COVID-19 infections. Attention to these features can help optimize patient management.

Not hepatic infarction: Cold quadrate sign.

A 50-year-old male presented with bilateral lower extremity plain is found to have a wedge-shape hypodense region in the hepatic quadrate lobe. The hypoenhancement was thought to be a result of systemic-portal venous shunting due to IVC obstruction, a "cold" version of the classically described hot quadrate sign. Follow-up CT confirmed the diagnosis. Venous drainage pathway for both hot and cold quadrate signs is discussed.

Association between circulating tumor DNA burden and disease burden in patients with ALK-positive lung cancer.

BACKGROUND: Plasma genotyping is an emerging approach for the identification of genetic alterations mediating resistance to anaplastic lymphoma kinase (ALK)-targeted therapy. The authors reviewed plasma genotyping and imaging findings to assess the correlation between circulating tumor DNA (ctDNA) burden and disease burden in patients with ALK-positive lung cancer. METHODS: The authors analyzed 97 plasma specimens from 75 patients with ALK-positive lung cancer to identify ALK and non-ALK alterations. Disease burden was estimated by tabulating lesions per organ and calculating lesion diameters, areas, and volumes. Disease burden was correlated with the allelic frequency (AF) of plasma alterations. RESULTS: The mean interval between plasma collection and imaging was 8 days. ctDNA was detected in approximately 85% of plasma specimens. An ALK fusion and ALK mutation were detected in 79% and 76%, respectively, of plasma specimens. Using the maximum plasma alteration AF and maximum ALK alteration AF as independent surrogates of ctDNA burden, a higher disease burden measurement on imaging was found to be associated with higher ctDNA burden. Total body and extrathoracic tumor volume but not intrathoracic tumor volume correlated with ctDNA burden. Of all the disease sites assessed, the ctDNA burden correlated most with involvement of the liver, bones, and adrenal glands. Despite being the defining alteration in ALK-positive lung cancer, isolated plasma ALK fusion AF did not perform as well as the maximum plasma alteration AF or maximum ALK alteration AF for correlating tumor burden. CONCLUSIONS: In patients with ALK-positive lung cancer, the maximum plasma alteration AF and maximum ALK alteration AF correlate with the extrathoracic burden of disease and are more predictive of tumor burden compared with the ALK fusion AF alone. LAY SUMMARY: Analysis of genetic material shed from cancer cells into the circulation offers insights into the molecular composition of tumors. The circulating tumor DNA (ctDNA) varies over time and across individuals and is impacted by the distribution of disease. Herein, the authors estimated tumor burden on imaging and correlated it with ctDNA by calculating the maximum allelic frequency. The current study findings demonstrated that the greatest correlation exists between extrathoracic, extracranial tumor burden (particularly involvement of the liver, adrenal glands, or bones) and ctDNA burden, suggesting a biological basis for the interpatient and temporal intrapatient differences in ctDNA yield that have been described in previous studies.

Vascular magnetic resonance angiography techniques.

Magnetic resonance angiography (MRA) denotes a unique option for the evaluation of peripheral vasculature due to its noninvasive nature, lack of ionizing radiation exposure, potential for non-contrast examination, and ability for generating volumetric representations that showcase vascular pathology. The constant evolution of the available MRA techniques, however, makes understanding and determining an optimal imaging protocol difficult. Here we present a brief overview of the major MRA sequence options, their major weaknesses and strengths, and related imaging considerations. Understanding the technical underpinnings of the various MRA methods helps with recognition of common imaging issues and artifacts and rendering clinically relevant interpretations.

Systematic review of civilian intravascular ballistic embolism reports during the last 30 years.

BACKGROUND: Intravascular ballistic embolization is a rare complication of missile injury. Because of its rarity, much remains to be known about its presentation, pathophysiology, complications, and management. In this study, we analyze case reports of ballistic embolization in the last 30 years and available cases from our institution to determine the likely patient, the nature of the embolization, the possible complications, and a general management strategy. METHODS: A PubMed search was performed in search of missile embolization cases from 1988 to 2018 in the English language, including only cases of intravascular emboli. Cases resulting from combat and explosive devices were excluded. In addition, five cases from our institution were included in the analysis. RESULTS: A total of 261 cases were analyzed. The most common presentation was that of a young man (reflecting the demographics of those sustaining gunshot wound injuries) with injury to the anterior torso from a single gunshot wound. Venous entry was most common, most often through large-caliber vessels. There was roughly equal involvement of the right and left circulation. Left circulation emboli were frequently symptomatic, with ischemia being the most frequent sequela. In contrast, a right circulation embolus was rarely associated with significant complications. CONCLUSIONS: Despite its rarity, ballistic embolization should be considered in gunshot injury with known large-vessel injury when an exit wound is not identified. In particular, signs of ischemia distant from the injury site warrant timely investigation to maximize tissue salvageability. We present a management strategy model for consideration.

Antenatal Synthetic Glucocorticoid Exposure at Human Therapeutic Equivalent Doses Predisposes Middle-Age Male Offspring Baboons to an Obese Phenotype That Emerges With Aging.

INTRODUCTION: Women threatening premature delivery receive synthetic glucocorticoids (sGC) to accelerate fetal lung maturation, reducing neonatal mortality and morbidity. Few investigations have explored potential long-term offspring side effects. We previously reported increased pericardial fat and liver lipids in 10-year-old (human equivalent 40 years) male baboons exposed to 3 antenatal sGC courses. We hypothesized middle-aged sGC male offspring show obesity-related morphometric changes. METHODS: Pregnant baboons received courses of 2 betamethasone injections (175 µg·kg-1·d-1 intramuscular) at 0.6, 0.64, and 0.68 gestation. At 10 to 12.5 years, we measured morphometrics and serum lipids in 5 sGC-exposed males and 10 age-matched controls. We determined whether morphometric parameters predicted amount of pericardial fat or lipids. Life-course serum lipids were measured in 25 males (7-23 years) providing normal regression formulas to compare sGC baboons' lipid biological and chronological age. RESULTS: Birth weights were similar. When studied, sGC-exposed males showed a steeper weight increase from 8 to 12 years and had increased waist and hip circumferences, neck and triceps skinfolds, and total and low-density lipoprotein cholesterol. Triceps skinfold correlated with apical and midventricular pericardial fat thickness, hip and waist circumferences with insulin. CONCLUSIONS: Triceps skinfold and waist and hip circumferences are useful biomarkers for identifying individuals at risk for obesity and metabolic dysregulation following fetal sGC exposure. Prenatal sGC exposure predisposes male offspring to internal adiposity, greater body size, and increased serum lipids. Results provide further evidence for developmental programming by fetal sGC exposure and call attention to potential emergence of adverse life-course effects.

Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.).

KEY POINTS: Life course changes in cardiovascular function in a non-human primate have been comprehensively characterized. Age-related declines in normalized left ventricular stroke volume and cardiac output were found with corresponding decreases in biventricular ejection fractions and filling rates. There were age-related decreases in male and female baboon normalized left ventricular myocardial mass index, which declined at similar rates. Systolic functional declines in right ventricular function were observed with age, similar to the left ventricle. Sex differences were found in the rates and directions of right ventricular volume changes along with decreased end-systolic right ventricular sphericity. The results validate the baboon as an appropriate model for translational studies of cardiovascular functional decline with ageing. ABSTRACT: Previous studies reported cardiac function declines with ageing. This study determined changes in biventricular cardiac function in a well-characterized baboon model. Cardiac magnetic resonance imaging measured key biventricular parameters in 47 baboons (22 female, age 4-23 years). ANCOVA assessed sex and age changes with P < 0.05 deemed significant. Stroke volume, cardiac output and other cardiac functional parameters were normalized to body surface area. There were similar, age-related rates of decrease in male (M) and female (F) normalized left ventricular (LV) myocardial mass index (M: -1.2 g m-2  year-1 , F: -0.9 g m-2  year-1 ). LV ejection fraction declined at -0.96% year-1 (r = -0.43, P = 0.002) and right ventricular (RV) ejection fraction decreased at -1.2% year-1 (r = -0.58, P < 0.001). Normalized LV stroke volume fell at -1.1 ml m-2  year-1 (r = -0.47, P = 0.001), normalized LV ejection rate at -3.8 ml s-1  m-2  year-1 (r = -0.43, P < 0.005) and normalized LV filling rate at -4.1 ml s-1  m-2  year-1 (r = -0.44, P < 0.005). Also, RV wall thickening fraction decreased with age (slope = -1% year-1 , P = 0.008). RV ejection rate decreased at -3.6 ml s-1  m-2  year-1 (P = 0.002) and the normalized average RV filling rate dropped at -3.7 ml s-1  m-2  year-1 (P < 0.0001). End-systolic RV sphericity index also dropped with age (r = -0.33, P = 0.02). Many observed changes parallel previously reported data in human and animal studies. These measured biventricular functional declines in hearts with ageing from the closest experimental primate species to man underscore the utility of the baboon model for investigating mechanisms related to heart ageing.

Efficacy and safety of antenatal steroids.

Antenatal steroids (ANS) are among the most important and widely utilized interventions to improve outcomes for preterm infants. A significant body of evidence demonstrates improved outcomes in preterm infants (24-34 wk) delivered between 1 and 7 days after the administration of a single course of ANS. Moreover, ANS have the advantage of being widely available, low cost, and easily administered via maternal intramuscular injection. The use of ANS to mature the fetal lung is, however, not without contention. Their use in pregnancy is not FDA approved, and treatment doses and regimens remain largely unoptimized. Their mode of use varies considerably between countries, and there are lingering concerns regarding the safety of exposing the fetus to high doses of exogenous steroids. A significant proportion of women deliver outside the 1- to 7-day therapeutic window after ANS treatment, and this delay may be associated with an increased risk of adverse outcomes for both mother and baby. Today, animal-based studies are one means by which key questions of dosing and safety relating to ANS may be resolved, allowing for further refinement(s) of this important therapy. Complementary approaches using nonhuman primates, sheep, and rodents have provided invaluable advances to our understanding of how exogenous steroid exposure impacts fetal development. Focusing on these three major model groups, this review highlights the role of three key animal models (sheep, nonhuman primates, rodents) in the development of antenatal steroid therapy, and provides an up-to-date synthesis of current efforts to refine this therapy in an era of personalised medicine.