Cross-tissue organization of the fibroblast lineage.

Fibroblasts are non-haematopoietic structural cells that define the architecture of organs, support the homeostasis of tissue-resident cells and have key roles in fibrosis, cancer, autoimmunity and wound healing1. Recent studies have described fibroblast heterogeneity within individual tissues1. However, the field lacks a characterization of fibroblasts at single-cell resolution across tissues in healthy and diseased organs. Here we constructed fibroblast atlases by integrating single-cell transcriptomic data from about 230,000 fibroblasts across 17 tissues, 50 datasets, 11 disease states and 2 species. Mouse fibroblast atlases and a DptIRESCreERT2 knock-in mouse identified two universal fibroblast transcriptional subtypes across tissues. Our analysis suggests that these cells can serve as a reservoir that can yield specialized fibroblasts across a broad range of steady-state tissues and activated fibroblasts in disease. Comparison to an atlas of human fibroblasts from perturbed states showed that fibroblast transcriptional states are conserved between mice and humans, including universal fibroblasts and activated phenotypes associated with pathogenicity in human cancer, fibrosis, arthritis and inflammation. In summary, a cross-species and pan-tissue approach to transcriptomics at single-cell resolution has identified key organizing principles of the fibroblast lineage in health and disease.

International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults.

Langerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.

3D printed models are an accurate, cost-effective, and reproducible tool for quantifying terrestrial thermal environments.

Predicting ecological responses to rapid environmental change has become one of the greatest challenges of modern biology. One of the major hurdles in forecasting these responses is accurately quantifying the thermal environments that organisms experience. The distribution of temperatures available within an organism's habitat is typically measured using data loggers called operative temperature models (OTMs) that are designed to mimic certain properties of heat exchange in the focal organism. The gold standard for OTM construction in studies of terrestrial ectotherms has been the use of copper electroforming which creates anatomically accurate models that equilibrate quickly to ambient thermal conditions. However, electroformed models require the use of caustic chemicals, are often brittle, and their production is expensive and time intensive. This has resulted in many researchers resorting to the use of simplified OTMs that can yield substantial measurement errors. 3D printing offers the prospect of robust, easily replicated, morphologically accurate, and cost-effective OTMs that capture the benefits but alleviate the problems associated with electroforming. Here, we validate the use of OTMs that were 3D printed using several materials across eight lizard species of different body sizes and living in habitats ranging from deserts to tropical forests. We show that 3D printed OTMs have low thermal inertia and predict the live animal's equilibration temperature with high accuracy across a wide range of body sizes and microhabitats. Finally, we developed a free online repository and database of 3D scans (https://www.3dotm.org/) to increase the accessibility of this tool to researchers around the world and facilitate ease of production of 3D printed models. 3D printing of OTMs is generalizable to taxa beyond lizards. If widely adopted, this approach promises greater accuracy and reproducibility in studies of terrestrial thermal ecology and should lead to improved forecasts of the biological impacts of climate change.

A diminutive snake species can maintain regional heterothermy in both homogeneous and heterogeneous thermal environments.

Regional heterothermy is a pattern whereby different body regions are maintained at different temperatures, often to prioritize the function of certain body parts over others, or to maximize the function of organs and tissues that vary in thermal sensitivity. Regional heterothermy is relatively well understood in endotherms, where physiological mechanisms maintain heterogeneity. However, less is known about regional heterothermy in ectotherms, where behavioral mechanisms are more important for generating thermal variation. In particular, whether small and elongate ectotherms with high surface area to volume ratios such as diminutive snakes can maintain regional heterothermy, despite rapid thermal equilibration, is not yet known. We measured regional variation in body temperature and tested whether environmental heterogeneity is used to generate regional heterothermy in the ring-necked snake (Diadophis punctatus) using both field and laboratory studies. We found that ring-necked snakes have robust regional heterothermy in a variety of contexts, despite their small body size and elongate body shape. Temperature variation along the length of their bodies was not detectable when measured externally. However, snakes had higher mouth than cloacal temperatures both in the field and in laboratory thermal gradients. Further, this regional heterothermy was maintained even in ambient laboratory conditions, where the thermal environment was relatively homogeneous. Our results indicate that regional heterothermy in ring-necked snakes is not solely driven by environmental variation but is instead linked to physiological or morphological mechanisms that maintain regional variation in body temperature irrespective of environmental context.

Species differences in hormonally mediated gene expression underlie the evolutionary loss of sexually dimorphic coloration in Sceloporus lizards.

Phenotypic sexual dimorphism often involves the hormonal regulation of sex-biased expression for underlying genes. However, it is generally unknown whether the evolution of hormonally mediated sexual dimorphism occurs through upstream changes in tissue sensitivity to hormone signals, downstream changes in responsiveness of target genes, or both. Here, we use comparative transcriptomics to explore these possibilities in 2 species of Sceloporus lizards exhibiting different patterns of sexual dichromatism. Sexually dimorphic S. undulatus develops blue and black ventral coloration in response to testosterone, while sexually monomorphic S. virgatus does not, despite exhibiting similar sex differences in circulating testosterone levels. We administered testosterone implants to juveniles of each species and used RNAseq to quantify gene expression in ventral skin. Transcriptome-wide responses to testosterone were stronger in S. undulatus than in S. virgatus, suggesting species differences in tissue sensitivity to this hormone signal. Species differences in the expression of genes for androgen metabolism and sex hormone-binding globulin were consistent with this idea, but expression of the androgen receptor gene was higher in S. virgatus, complicating this interpretation. Downstream of androgen signaling, we found clear species differences in hormonal responsiveness of genes related to melanin synthesis, which were upregulated by testosterone in S. undulatus, but not in S. virgatus. Collectively, our results indicate that hormonal regulation of melanin synthesis pathways contributes to the development of sexual dimorphism in S. undulatus, and that changes in the hormonal responsiveness of these genes in S. virgatus contribute to the evolutionary loss of ventral coloration.

Sustained Drought, but Not Short-Term Warming, Alters the Gut Microbiomes of Wild Anolis Lizards.

As rising temperatures threaten biodiversity across the globe, tropical ectotherms are thought to be particularly vulnerable due to their narrow thermal tolerance ranges. Nevertheless, physiology-based models highlighting the vulnerability of tropical organisms rarely consider the contributions of their gut microbiota, even though microbiomes influence numerous host traits, including thermal tolerance. We combined field and lab experiments to understand the response of the slender anole lizard (Anolis apletophallus) gut microbiome to climatic shifts of various magnitude and duration. First, to examine the effects of long-term climate warming in the wild, we transplanted lizards from the mainland Panama to a series of warmer islands in the Panama Canal and compared their gut microbiome compositions after three generations of divergence. Next, we mimicked the effects of a short-term "heat-wave" by using a greenhouse experiment and explored the link between gut microbiome composition and lizard thermal physiology. Finally, we examined variation in gut microbiomes in our mainland population in the years both before and after a naturally occurring drought. Our results suggest that slender anole microbiomes are surprisingly resilient to short-term warming. However, both the taxonomic and predicted functional compositions of the gut microbiome varied by sampling year across all sites, suggesting that the drought may have had a regional effect. We provide evidence that short-term heat waves may not substantially affect the gut microbiota, while more sustained climate anomalies may have effects at broad geographic scales. IMPORTANCE As climate change progresses, it is crucial to understand how animals will respond to shifts in their local environments. One component of this response involves changes in the microbial communities living in and on host organisms. These "microbiomes" can affect many processes that contribute to host health and survival, yet few studies have measured changes in the microbiomes of wild organisms experiencing novel climatic conditions. We examined the effects of shifting climates on the gut microbiome of the slender anole lizard (Anolis apletophallus) by using a combination of field and laboratory studies, including transplants to warm islands in the Panama Canal. We found that slender anole microbiomes remain stable in response to short-term warming but may be sensitive to sustained climate anomalies, such as droughts. We discuss the significance of these findings for a species that is considered highly vulnerable to climate change.

Evolution of hormone-phenotype couplings and hormone-genome interactions.

When selection favors a new relationship between a cue and a hormonally mediated response, adaptation can proceed by altering the hormonal signal that is produced or by altering the phenotypic response to the hormonal signal. The field of evolutionary endocrinology has made considerable progress toward understanding the evolution of hormonal signals, but we know much less about the evolution of hormone-phenotype couplings, particularly at the hormone-genome interface. We briefly review and classify the mechanisms through which these hormone-phenotype couplings likely evolve, using androgens and their receptors and genomic response elements to illustrate our view. We then present two empirical studies of hormone-phenotype couplings, one rooted in evolutionary quantitative genetics and another in comparative transcriptomics, each focused on the regulation of sexually dimorphic phenotypes by testosterone (T) in the brown anole lizard (Anolis sagrei). First, we illustrate the potential for hormone-phenotype couplings to evolve by showing that coloration of the dewlap (an ornament used in behavioral displays) exhibits significant heritability in its responsiveness to T, implying that anoles harbor genetic variance in the architecture of hormonal pleiotropy. Second, we combine T manipulations with analyses of the liver transcriptome to ask whether and how statistical methods for characterizing modules of co-expressed genes and in silico techniques for identifying androgen response elements (AREs) can improve our understanding of hormone-genome interactions. We conclude by emphasizing important avenues for future work at the hormone-genome interface, particularly those conducted in a comparative evolutionary framework.

Genetic mechanisms and correlational selection structure trait variation in a coral snake mimic.

Covariation among traits shapes both phenotypic evolution and ecological interactions across space and time. However, rampant geographical variation in the strength and direction of such correlations can be particularly difficult to explain through generalized mechanisms. By integrating population genomics, surveys of natural history collections and spatially explicit analyses, we tested multiple drivers of trait correlations in a coral snake mimic that exhibits remarkable polymorphism in mimetic and non-mimetic colour traits. We found that although such traits co-occur extensively across space, correlations were best explained by a mixture of genetic architecture and correlational selection, rather than by any single mechanism. Our findings suggest that spatially complex trait distributions may be driven more by the simple interaction between multiple processes than by complex variation in one mechanism alone. These interactions are particularly important in mimicry systems, which frequently generate striking geographical variation and genetic correlations among colour pattern traits.

Elevation, oxygen, and the origins of viviparity.

Research focused on understanding the evolutionary factors that shape parity mode evolution among vertebrates have long focused on squamate reptiles (snakes and lizards), which contain all but one of the evolutionary transitions from oviparity to viviparity among extant amniotes. While most hypotheses have focused on the role of cool temperatures in favoring viviparity in thermoregulating snakes and lizards, there is a growing appreciation in the biogeographic literature for the importance of lower oxygen concentrations at high elevations for the evolution of parity mode. However, the physiological mechanisms underlying how hypoxia might reduce fitness, and how viviparity can alleviate this fitness decrement, has not been systematically evaluated. We qualitatively evaluated previous research on reproductive and developmental physiology, and found that (1) hypoxia can negatively affect fitness of squamate embryos, (2) oxygen availability in the circulatory system of adult lizards can be similar or greater than an egg, and (3) gravid females can possess adaptive phenotypic plasticity in response to hypoxia. These findings suggest that the impact of hypoxia on the development and physiology of oviparous and viviparous squamates would be a fruitful area of research for understanding the evolution of viviparity. To that end, we propose an integrative research program for studying hypoxia and the evolution of viviparity in squamates.

Sex-specific microhabitat use is associated with sex-biased thermal physiology in Anolis lizards.

If fitness optima for a given trait differ between males and females in a population, sexual dimorphism may evolve. Sex-biased trait variation may affect patterns of habitat use, and if the microhabitats used by each sex have dissimilar microclimates, this can drive sex-specific selection on thermal physiology. Nevertheless, tests of differences between the sexes in thermal physiology are uncommon, and studies linking these differences to microhabitat use or behavior are even rarer. We examined microhabitat use and thermal physiology in two ectothermic congeners that are ecologically similar but differ in their degree of sexual size dimorphism. Brown anoles (Anolis sagrei) exhibit male-biased sexual size dimorphism and live in thermally heterogeneous habitats, whereas slender anoles (Anolis apletophallus) are sexually monomorphic in body size and live in thermally homogeneous habitats. We hypothesized that differences in habitat use between the sexes would drive sexual divergence in thermal physiology in brown anoles, but not slender anoles, because male and female brown anoles may be exposed to divergent microclimates. We found that male and female brown anoles, but not slender anoles, used perches with different thermal characteristics and were sexually dimorphic in thermal tolerance traits. However, field-active body temperatures and behavior in a laboratory thermal arena did not differ between females and males in either species. Our results suggest that sexual dimorphism in thermal physiology can arise from phenotypic plasticity or sex-specific selection on traits that are linked to thermal tolerance, rather than from direct effects of thermal environments experienced by males and females.

Langerhans cell histiocytosis with lung involvement in isolation and multisystem disease: Staging, natural history, and comparative survival.

Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that can involve the lungs as single system (LCH-SSL) or multisystem disease (LCH-MSL). The role of full-body radiographic staging to determine whether patients have LCH-SSL or LCH-MSL is unclear. Long-term outcomes of LCH-SSL versus LCH-MSL and multisystem without lung involvement (LCH-MSNL) are unknown. A retrospective study of adult LCH patients seen at our center from January 2000 to 2020 was performed. In Part 1, we addressed utility of whole-body staging imaging among those presenting with isolated pulmonary signs or symptoms. Staging was defined as fluorodeoxyglucose positron emission tomography-computed tomography (CT) or whole-body CT obtained within 3 months of diagnosis. In Part 2, we examined the frequency of developing extra-pulmonary disease over time and mortality in patients with LCH-SSL. In Part 3, we compared the overall survival of LCH-SSL, LCH-MSL, and LCH-MSNL. Part 1: 240 patients with LCH were identified. A total of 112 (47%) had pulmonary signs or symptoms at presentation. Thirty-four (30%) underwent radiographic staging and only one showed evidence of extra-pulmonary disease. Part 2: 108 (45%) were LCH-SSL. Median follow-up duration of 4.5 years (95% confidence interval [CI]: 2.9-6.0). None developed extra-pulmonary disease. Part 3: 5-year survival: 94% (95% CI: 84%-98%) for LCH-SSL, 78% (95% CI: 59%-90%) for LCH-MSL, and 75% (95% CI: 53%-89%) for LCH-MSNL. LCH patients presenting with isolated pulmonary signs or symptoms rarely have extra-pulmonary involvement at the time of diagnosis and generally do not develop extra-pulmonary progression. LCH-SSL has the best overall survival, while LCH-MSL and LCH-MSNL have similar clinical outcomes.

Acclimatization in the physiological performance of an introduced ectotherm.

Phenotypic flexibility may facilitate range expansion by allowing organisms to maintain high levels of performance when introduced to novel environments. Phenotypic flexibility, such as reversible acclimatization, permits organisms to achieve high performance over a wide range of environmental conditions, without the costly allocation or acquisition tradeoffs associated with behavioral thermoregulation, which may expedite range expansion in introduced species. The northern curly-tailed lizard, Leiocephalus carinatus, was introduced to the USA in the 1940s and is now established in southern Florida. We measured bite force and the thermal sensitivity of sprinting of L. carinatus during the winter and spring to determine how morphology and performance varied seasonally. We found evidence of seasonal variation in several aspects of physiological performance. Lizards sampled in spring sprinted faster and tolerated higher temperatures, while lizards sampled in winter had high performance over a wider range of temperatures. Furthermore, seasonal differences in physiology were only detected after generating thermal reaction norms. Both sprint and bite force performance did not differ seasonally when solely comparing performance at a common temperature. No seasonal relationships between morphology and performance were detected. Our results suggest that L. carinatus may use reversible acclimatization to maintain high levels of performance across seasons not typically experienced within their native range. Thermal physiology plasticity may ameliorate the impacts of sub-optimal temperatures on performance without the cost of behavioral thermoregulation. Our work highlights the importance of utilizing reaction norms when evaluating performance and the potential ecological impacts of introduced species.

Ectoparasite extinction in simplified lizard assemblages during experimental island invasion.

Introduced species can become invasive, damaging ecosystems and disrupting economies through explosive population growth. One mechanism underlying population expansion in invasive populations is 'enemy release', whereby the invader experiences relaxation of agonistic interactions with other species, including parasites. However, direct observational evidence of release from parasitism during invasion is rare. We mimicked the early stages of invasion by experimentally translocating populations of mite-parasitized slender anole lizards (Anolis apletophallus) to islands that varied in the number of native anoles. Two islands were anole-free prior to the introduction, whereas a third island had a resident population of Gaige's anole (Anolis gaigei). We then characterized changes in trombiculid mite parasitism over multiple generations post-introduction. We found that mites rapidly went extinct on one-species islands, but that lizards introduced to the two-species island retained mites. After three generations, the two-species island had the highest total density and biomass of lizards, but the lowest density of the introduced species, implying that the 'invasion' had been less successful. This field-transplant study suggests that native species can be 'enemy reservoirs' that facilitate co-colonization of ectoparasites with the invasive host. Broadly, these results indicate that the presence of intact and diverse native communities may help to curb invasiveness.

Diffuse Pulmonary Ossification on High-Resolution Computed Tomography in Idiopathic Pulmonary Fibrosis, Systemic Sclerosis-Related Interstitial Lung Disease, and Chronic Hypersensitivity Pneumonitis: A Comparative Study.

OBJECTIVE: The aim of the study was to compare the prevalence of diffuse pulmonary ossification (DPO) in idiopathic pulmonary fibrosis (IPF), systemic sclerosis (SSc)-related interstitial lung disease (ILD), and chronic hypersensitivity pneumonitis (HP). METHODS: High-resolution computed tomography (HRCT) from 71 IPF, 67 SSc-ILD, and 75 HP cases were independently evaluated by 2 thoracic radiologists blinded to patient data. Studies were assessed for the presence of DPO, HRCT scanning pattern, stigmata of granulomatous infection, and honeycombing. RESULTS: The prevalence of DPO was significantly higher in cases of IPF and SSc compared with HP, although there was no significant difference in prevalence between the IPF and SSc groups, even when accounting for the presence of prior granulomatous infection. Interobserver agreement for the presence of DPO was substantial. CONCLUSIONS: Although prevalence DPO on HRCT varies between some forms of ILD, the use of DPO to influence characterization of ILD should be considered with caution.

Thermal ecology and physiology of an elongate and semi-fossorial arthropod, the bark centipede.

Organismal performance is strongly linked to temperature because of the fundamental thermal dependence of chemical reaction rates. However, the relationship between the environment and body temperature can be altered by morphology and ecology. In particular, body size and body shape can impact thermal inertia, as high surface area to volume ratios will possess low thermal mass. Habitat type can also influence thermal physiology by altering the opportunity for thermoregulation. We studied the thermal ecology and physiology of an elongate invertebrate, the bark centipede (Scolopocryptops sexspinosus). We characterized field body temperature and environmental temperature distributions, measured thermal tolerance limits, and constructed thermal performance curves for a population in southern Georgia. We found evidence that bark centipedes behaviorally thermoregulate, despite living in sheltered microhabitats, and that performance was maintained over a broad range of temperatures (over 20 °C). However, both the thermal optimum for performance and upper thermal tolerance were much higher than mean body temperature in the field. Together, these results suggest that centipedes can thermoregulate and maintain performance over a broad range of temperatures but are sensitive to extreme temperatures. More broadly, our results suggest that wide performance breadth could be an adaptation to thermal heterogeneity in space and time for a species with low thermal inertia.

Environmental heterogeneity and not vicariant biogeographic barriers generate community-wide population structure in desert-adapted snakes.

Genetic structure can be influenced by local adaptation to environmental heterogeneity and biogeographic barriers, resulting in discrete population clusters. Geographic distance among populations, however, can result in continuous clines of genetic divergence that appear as structured populations. Here, we evaluate the relevant importance of these three factors over a landscape characterized by environmental heterogeneity and the presence of a hypothesized biogeographic barrier in producing population genetic structure within 13 codistributed snake species using a genomic data set. We demonstrate that geographic distance and environmental heterogeneity across western North America contribute to population genomic divergence. Surprisingly, landscape features long thought to contribute to biogeographic barriers play little role in divergence community wide. Our results suggest that isolation by environment is the most important contributor to genomic divergence. Furthermore, we show that models of population clustering that incorporate spatial information consistently outperform nonspatial models, demonstrating the importance of considering geographic distances in population clustering. We argue that environmental and geographic distances as drivers of community-wide divergence should be explored before assuming the role of biogeographic barriers.

Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide.

In the human genome, translation initiation from non-AUG codons plays an important role in various gene regulation programs. However, mechanisms regulating the non-AUG initiation rate remain poorly understood. Here, we show that the non-AUG initiation rate is nearly consistent under a fixed nucleotide context in various human and insect cells. Yet, it ranges from <1% to nearly 100% compared to AUG translation, depending on surrounding sequences, including Kozak, and possibly additional nucleotide contexts. Mechanistically, this range of non-AUG initiation is controlled in part, by the eIF5-mimic protein (5MP). 5MP represses non-AUG translation by competing with eIF5 for the Met-tRNAi-binding factor eIF2. Consistently, eIF5 increases, whereas 5MP decreases translation of NAT1/EIF4G2/DAP5, whose sole start codon is GUG. By modulating eIF5 and 5MP1 expression in combination with ribosome profiling we identified a handful of previously unknown non-AUG initiation sites, some of which serve as the exclusive start codons. If the initiation rate for these codons is low, then an AUG-initiated downstream ORF prevents the generation of shorter, AUG-initiated isoforms. We propose that the homeostasis of the non-AUG translatome is maintained through balanced expression of eIF5 and 5MP.

High-pitch versus standard mode CT pulmonary angiography: a comparison of indeterminate studies.

PURPOSE: To compare the causes of indeterminate CT pulmonary angiograms using standard mode and high-pitch mode, and determine at what level of the pulmonary arterial tree studies were non-diagnostic. METHODS: IRB approval was obtained. A retrospective review of patients at our institution who underwent a CT pulmonary angiogram, between November 1, 2015 and February 10, 2016 was performed. CT pulmonary angiograms using both high-pitch mode and standard mode were evaluated with positive and indeterminate rates calculated. Causes of indeterminate studies and the level of the pulmonary arterial tree at which the study became non-diagnostic were determined by a board certified radiologist by looking at the images of each indeterminate study. The indeterminate rates were compared between high-pitch and standard modes using a generalized estimating equation. RESULTS: Five hundred fifty-nine CT pulmonary angiograms using high-pitch mode were evaluated, while 661 standard mode scans were evaluated. 69/559 (12.3%) scans with high-pitch mode were positive and 84/661 (12.7%) scans with standard mode were positive (not statistically significant, p > 0.05). There was a higher rate of indeterminate scans with standard mode compared to the high-pitch mode (80 [12.1%] standard vs. 25 [4.5%] high-pitch, p value < 0.0001). Findings were indeterminate at the lobar level in 4 (16%), at the segmental level in 11 (44%), and at the subsegmental level in 10 (40%) using high-pitch mode. The most common causes of an indeterminate scan using high-pitch mode were motion in 11 (44%), transient interruption of contrast in 6 (24%), and contrast timing in 5 (20%). Findings were indeterminate at the main pulmonary artery level in 1 (1.3%), at the lobar level in 13 (16.3%), at the segmental level in 28 (35.0%), and at the subsegmental level in 38 (47.5%) using the standard mode. The most common causes of an indeterminate scan using the standard mode were motion in 53 (66.3%), transient interruption of contrast in 19 (23.8%), and contrast timing in 15 (18.8%). CONCLUSIONS: High-pitch mode results in statistically significant fewer indeterminate studies compared with standard mode. Furthermore, there were statistically significant fewer indeterminate studies due to motion artifact with high-pitch mode compared with standard mode.

Spontaneous Pneumomediastinum in Connective Tissue Diseases.

BACKGROUND: Spontaneous pneumomediastinum (SP) is an uncommon disorder but has been described in cases with connective tissue diseases (CTDs), most commonly dermatomyositis and polymyositis. We aimed to explore this relationship by analyzing the characteristics of CTD patients with SP. METHODS: Using a computer-assisted search, we identified 25 patients with CTD and SP evaluated between January 1997 and December 2016 at our institution. Clinicoradiologic characteristics, treatment, and outcomes were extracted and chest computed tomography studies analyzed. RESULTS: We identified 25 patients with CTD and SP. Median (range) age at SP occurrence was 55 (18-82) years, and 60% of the patients were women. Smoking history was present in 37%. Spontaneous pneumomediastinum was symptomatic in 56% of patients. Eighteen patients (72%) had a known CTD diagnosis, and 20 patients (80%) manifested radiologic evidence of interstitial lung disease. Spontaneous pneumomediastinum diagnosis was achieved with chest radiography in 20% of cases and chest computed tomography in the other cases. Spontaneous pneumomediastinum was managed with expectant observation alone in 22 cases (88%). Four patients (16%) had concomitant pneumothorax, 1 of whom required chest tube drainage. There were no deaths attributable to SP during the median (range) follow-up of 13 (0-174) months. Cumulative survival was 52% at 1 year and 40% at 2 years. CONCLUSIONS: Spontaneous pneumomediastinum is an uncommon manifestation of CTD and usually occurs in the presence of interstitial lung disease. Although SP seems to be associated with a relatively benign short-term course, occurrence of SP in CTD patients may be a poor prognostic factor.

CT Features of the Usual Interstitial Pneumonia Pattern: Differentiating Connective Tissue Disease-Associated Interstitial Lung Disease From Idiopathic Pulmonary Fibrosis.

OBJECTIVE: A substantial proportion of cases of usual interstitial pneumonia (UIP) are due to connective tissue disease (CTD)-associated interstitial lung disease (ILD). The purpose of this study was to determine whether specific CT findings can help differentiate a UIP pattern of CTD-ILD from a UIP pattern of idiopathic pulmonary fibrosis (IPF) and whether these signs are associated with survival. MATERIALS AND METHODS: Adults visiting an ILD clinic from 2006 to 2015 enrolled in a research registry with a multidisciplinary diagnosis of CTD-ILD or IPF and a UIP pattern at high-resolution CT were included in the study. In these subjects with CT findings of UIP due to either IPF or CTD-ILD, three CT findings anecdotally associated with CTD-ILD were assessed for diagnostic accuracy: the "straight-edge" sign, the "exuberant honeycombing" sign, and the "anterior upper lobe" sign. Survival assessments were performed with univariate and multivariable techniques. RESULTS: The subjects included 63 patients who had CTD-ILD and 133 patients who had IPF with a UIP pattern at CT. All three CT signs were significantly more common in subjects with CTD-ILD than those with IPF (prevalence, 22.2-25.4% for CTD-ILD, 6.0-12.8% for IPF; p = 0.028 to < 0.001). The highest specificity (94.0%) and sensitivity (25.4%) were seen for the straight-edge sign. No CT sign was associated with survival in multivariable analysis. CONCLUSION: Although UIP is usually associated with IPF, the index of suspicion for CTD-ILD should be raised in the care of patients with any of the three CT signs. A thorough workup for CTD-ILD should be pursued, including referral to the rheumatology department.