Impact of thrombocytopenia on bleeding and thrombotic outcomes in adults with cancer-associated splanchnic vein thrombosis.

Malignancy is a risk factor for splanchnic vein thrombosis (SpVT). Data on the natural history of cancer-associated SpVT are limited. This was a single-center retrospective cohort study of 581 adult patients with cancer and SpVT. We aimed to characterize the impact of thrombocytopenia on major bleeding and progression or recurrence of SpVT within one year of initial cancer-associated SpVT diagnosis. Baseline thrombocytopenia (platelet < 100,000/uL within 15 days of SpVT diagnosis) was present in 39.5% of patients. A total of 39.2% of patients received therapeutic anticoagulation within two weeks of SpVT diagnosis. The cumulative once-year incidence of major bleeding was 10.7% (95% CI: 8.2-13.2), and for SpVT recurrence/progression was 16.2% (95% CI: 13.2-19.2). In multivariable regression analysis, therapeutic anticoagulation was associated with increased major bleeding (aRR: 1.74, 95% CI: 1.08-2.81) and decreased progression/recurrence of SpVT (aRR: 0.55, 95% CI: 0.35-0.86). Baseline thrombocytopenia was not independently associated with either major bleeding (aRR: 0.76, 95% CI: 0.43-1.34) or progression/recurrence of SpVT (aRR: 1.14, 95% CI: 0.73-1.78). A secondary analysis using inverse probability of treatment weighting with propensity scores for baseline thrombocytopenia corroborated that patients with thrombocytopenia did not have increased bleeding risk (aHR: 0.81, 95% CI: 0.48-1.39). Multivariable analysis treating platelets as a time varying covariate also did not reveal an association with major bleeding (aHR: 0.89, 95% CI: 0.55-1.45). Bleeding and thrombosis progression were frequent in patients with cancer-associated SpVT. Anticoagulation was associated with increased major bleeding and decreased thrombotic progression; thrombocytopenia did not impact outcomes.

Waves of Colonization and Gene Flow in a Great Speciator.

Secondary contact between previously allopatric lineages offers a test of reproductive isolating mechanisms that may have accrued in isolation. Such instances of contact can produce stable hybrid zones-where reproductive isolation can further develop via reinforcement or phenotypic displacement-or result in the lineages merging. Ongoing secondary contact is most visible in continental systems, where steady input from parental taxa can occur readily. In oceanic island systems, however, secondary contact between closely related species of birds is relatively rare. When observed on sufficiently small islands, relative to population size, secondary contact likely represents a recent phenomenon. Here, we examine the dynamics of a group of birds whose apparent widespread hybridization influenced Ernst Mayr's foundational work on allopatric speciation: the whistlers of Fiji (Aves: Pachycephala). We demonstrate two clear instances of secondary contact within the Fijian archipelago, one resulting in a hybrid zone on a larger island, and the other resulting in a wholly admixed population on a smaller, adjacent island. We leveraged low genome-wide divergence in the hybrid zone to pinpoint a single genomic region associated with observed phenotypic differences. We use genomic data to present a new hypothesis that emphasizes rapid plumage evolution and post-divergence gene flow.

Extraordinary levels of per- and polyfluoroalkyl substances (PFAS) in vertebrate animals at a New Mexico desert oasis: Multiple pathways for wildlife and human exposure.

Per- and polyfluoroalkyl substances (PFAS) in the environment pose persistent and complex threats to human and wildlife health. Around the world, PFAS point sources such as military bases expose thousands of populations of wildlife and game species, with potentially far-reaching implications for population and ecosystem health. But few studies shed light on the extent to which PFAS permeate food webs, particularly ecologically and taxonomically diverse communities of primary and secondary consumers. Here we conducted >2000 assays to measure tissue-concentrations of 17 PFAS in 23 species of mammals and migratory birds at Holloman Air Force Base (AFB), New Mexico, USA, where wastewater catchment lakes form biodiverse oases. PFAS concentrations were among the highest reported in animal tissues, and high levels have persisted for at least three decades. Twenty of 23 species sampled at Holloman AFB were heavily contaminated, representing middle trophic levels and wetland to desert microhabitats, implicating pathways for PFAS uptake: ingestion of surface water, sediments, and soil; foraging on aquatic invertebrates and plants; and preying upon birds or mammals. The hazardous long carbon-chain form, perfluorooctanosulfonic acid (PFOS), was most abundant, with liver concentrations averaging >10,000 ng/g wet weight (ww) in birds and mammals, respectively, and reaching as high 97,000 ng/g ww in a 1994 specimen. Perfluorohexanesulfonic acid (PFHxS) averaged thousands of ng/g ww in the livers of aquatic birds and littoral-zone house mice, but one order of magnitude lower in the livers of upland desert rodent species. Piscivores and upland desert songbirds were relatively uncontaminated. At control sites, PFAS levels were strikingly lower on average and different in composition. In sum, legacy PFAS at this desert oasis have permeated local aquatic and terrestrial food webs across decades, severely contaminating populations of resident and migrant animals, and exposing people via game meat consumption and outdoor recreation.

Specimen collection is essential for modern science.

Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.

Genomic signatures of convergent shifts to plunge-diving behavior in birds.

Understanding the genetic basis of convergence at broad phylogenetic scales remains a key challenge in biology. Kingfishers (Aves: Alcedinidae) are a cosmopolitan avian radiation with diverse colors, diets, and feeding behaviors-including the archetypal plunge-dive into water. Given the sensory and locomotor challenges associated with air-water transitions, kingfishers offer a powerful opportunity to explore the effects of convergent behaviors on the evolution of genomes and phenotypes, as well as direct comparisons between continental and island lineages. Here, we use whole-genome sequencing of 30 diverse kingfisher species to identify the genomic signatures associated with convergent feeding behaviors. We show that species with smaller ranges (i.e., on islands) have experienced stronger demographic fluctuations than those on continents, and that these differences have influenced the dynamics of molecular evolution. Comparative genomic analyses reveal positive selection and genomic convergence in brain and dietary genes in plunge-divers. These findings enhance our understanding of the connections between genotype and phenotype in a diverse avian radiation.

Mitonuclear discordance results from incomplete lineage sorting, with no detectable evidence for gene flow, in a rapid radiation of Todiramphus kingfishers.

Many organisms possess multiple discrete genomes (i.e. nuclear and organellar), which are inherited separately and may have unique and even conflicting evolutionary histories. Phylogenetic reconstructions from these discrete genomes can yield different patterns of relatedness, a phenomenon known as cytonuclear discordance. In many animals, mitonuclear discordance (i.e. discordant evolutionary histories between the nuclear and mitochondrial genomes) has been widely documented, but its causes are often considered idiosyncratic and inscrutable. We show that a case of mitonuclear discordance in Todiramphus kingfishers can be explained by extensive genome-wide incomplete lineage sorting (ILS), likely a result of the explosive diversification history of this genus. For these kingfishers, quartet frequencies reveal that the nuclear genome is dominated by discordant topologies, with none of the internal branches in our consensus nuclear tree recovered in >50% of genome-wide gene trees. Meanwhile, a lack of inter-species shared ancestry, non-significant pairwise tests for gene flow, and little evidence for meaningful migration edges between species, leads to the conclusion that gene flow cannot explain the mitonuclear discordance we observe. This lack of evidence for gene flow combined with evidence for extensive genome-wide gene tree discordance, a hallmark of ILS, leads us to conclude that the mitonuclear discordance we observe likely results from ILS, specifically deep coalescence of the mitochondrial genome. Based on this case study, we hypothesize that similar demographic histories in other 'great speciator' taxa across the Indo-Pacific likely predispose these groups to high levels of ILS and high likelihoods of mitonuclear discordance.

Complex plumages spur rapid color diversification in kingfishers (Aves: Alcedinidae).

Colorful signals in nature provide some of the most stunning examples of rapid phenotypic evolution. Yet, studying color pattern evolution has been historically difficult owing to differences in perceptual ability of humans and analytical challenges with studying how complex color patterns evolve. Island systems provide a natural laboratory for testing hypotheses about the direction and magnitude of phenotypic change. A recent study found that plumage colors of island species are darker and less complex than continental species. Whether such shifts in plumage complexity are associated with increased rates of color evolution remains unknown. Here, we use geometric morphometric techniques to test the hypothesis that plumage complexity and insularity interact to influence color diversity in a species-rich clade of colorful birds-kingfishers (Aves: Alcedinidae). In particular, we test three predictions: (1) plumage complexity enhances interspecific rates of color evolution, (2) plumage complexity is lower on islands, and (3) rates of plumage color evolution are higher on islands. Our results show that more complex plumages result in more diverse colors among species and that island species have higher rates of color evolution. Importantly, we found that island species did not have more complex plumages than their continental relatives. Thus, complexity may be a key innovation that facilitates evolutionary response of individual color patches to distinct selection pressures on islands, rather than being a direct target of selection itself. This study demonstrates how a truly multivariate treatment of color data can reveal evolutionary patterns that might otherwise go unnoticed.

Birds are among the most colorful animals on Earth. The different patterns and colors displayed on their feathers help them to identify their own species, attract mates or hide from predators. The bright plumages of birds are achieved through either pigments (such as reds and yellows) or structures (such as blues, greens or ultraviolet) inside feathers, or through a combination of both pigments and structures. Variation in the diversity of color patterns over time can give a helpful insight into the rate of evolution of a species. For example, structural colors evolve more quickly than pigment-based ones and can therefore be a key feature involved in species recognition or mate attraction. Studying the evolution of plumage patterns has been challenging due to differences in the vision of humans and birds. However, recent advances in technology have enabled researchers to map the exact wavelengths of the colors that make up the patterns, allowing for rigorous comparison of plumage color patterns across different individuals and species. To gain a greater understanding of how plumage color patterns evolve in birds, Eliason et al. studied kingfishers, a group of birds known for their complex and variable color patterns, and their worldwide distribution. The experiments analyzed the plumage color patterns of 72 kingfisher species (142 individual museum specimens) from both mainland and island populations by quantifying the amount of different wavelengths of light reflecting from a feather and accounting for relationships among species and among feather patches. The analyzes showed that having more complex patterns leads to a greater accumulation of plumage colors over time, supporting the idea that complex plumages provide more traits for natural or sexual selection to act upon. Moreover, in upper parts of the bodies, such as the back, the plumage varied more across the different species and evolved faster than in ventral parts, such as the belly or throat. This indicates that sexual selection may be the evolutionary force driving variation in more visible areas, such as the back, while patterns in the ventral part of the body are more important for kin recognition. Eliason et al. further found no differences in plumage complexity between kingfishers located in island or mainland habitats, suggesting that the isolation of the island and the different selection pressures this may bring does not impact the complexity of color patterns. However, kingfisher species located on islands did display higher rates of color evolution. This indicates that, regardless of the complexity of the plumage, island-specific pressures are driving rapid color diversification. Using a new multivariate approach, Eliason et al. have unearthed a pattern in plumage complexity that may otherwise have been missed and, for the first time, have linked differences in color pattern on individual birds with evolutionary differences across species. In doing so, they have provided a framework for future studies of color evolution. The next steps in this research would be to better understand why the island species are evolving more rapidly even though they do not have more complex plumage patterns and how the observed color differences relate to rapid rates of speciation.

A new genus for Dasycrotapha plateni and D. pygmaea (Aves: Zosteropidae).

N/A.

Genomic novelty within a "great speciator" revealed by a high-quality reference genome of the collared kingfisher (Todiramphus chloris collaris).

Islands are natural laboratories for studying patterns and processes of evolution. Research on island endemic birds has revealed elevated speciation rates and rapid phenotypic evolution in several groups (e.g. white-eyes, Darwin's finches). However, understanding the evolutionary processes behind these patterns requires an understanding of how genotypes map to novel phenotypes. To date, there are few high-quality reference genomes for species found on islands. Here, we sequence the genome of one of Ernst Mayr's "great speciators," the collared kingfisher (Todiramphus chloris collaris). Utilizing high molecular weight DNA and linked-read sequencing technology, we assembled a draft high-quality genome with highly contiguous scaffolds (scaffold N50 = 19 Mb). Based on universal single-copy orthologs, we estimated a gene space completeness of 96.6% for the draft genome assembly. The population demographic history analyses reveal a distinct pattern of contraction and expansion in population size throughout the Pleistocene. Comparative genomic analysis of gene family evolution revealed that species-specific and rapidly expanding gene families in the collared kingfisher (relative to other Coraciiformes) are mainly involved in the ErbB signaling pathway and focal adhesion. Todiramphus kingfishers are a species-rich group that has become a focus of speciation research. This draft genome will be a platform for future taxonomic, phylogeographic, and speciation research in the group. For example, target genes will enable testing of changes in sensory structures associated with changes in vision and taste genes across kingfishers.

Wallacean and Melanesian Islands Promote Higher Rates of Diversification within the Global Passerine Radiation Corvides.

The complex island archipelagoes of Wallacea and Melanesia have provided empirical data behind integral theories in evolutionary biology, including allopatric speciation and island biogeography. Yet, questions regarding the relative impact of the layered biogeographic barriers, such as deep-water trenches and isolated island systems, on faunal diversification remain underexplored. One such barrier is Wallace's Line, a significant biogeographic boundary that largely separates Australian and Asian biodiversity. To assess the relative roles of biogeographic barriers-specifically isolated island systems and Wallace's Line-we investigated the tempo and mode of diversification in a diverse avian radiation, Corvides (Crows and Jays, Birds-of-paradise, Vangas, and allies). We combined a genus-level data set of thousands of ultraconserved elements (UCEs) and a species-level, 12-gene Sanger sequence matrix to produce a well-resolved supermatrix tree that we leveraged to explore the group's historical biogeography and the effects of the biogeographic barriers on their macroevolutionary dynamics. The tree is well resolved and differs substantially from what has been used extensively for past comparative analyses within this group. We confirmed that Corvides, and its major constituent clades, arose in Australia and that a burst of dispersals west across Wallace's Line occurred after the uplift of Wallacea during the mid-Miocene. We found that dispersal across this biogeographic barrier was generally rare, though westward dispersals were two times more frequent than eastward dispersals. Wallacea's central position between Sundaland and Sahul no doubt acted as a bridge for island-hopping dispersal out of Australia, across Wallace's Line, to colonize the rest of Earth. In addition, we found that the complex island archipelagoes east of Wallace's Line harbor the highest rates of net diversification and are a substantial source of colonists to continental systems on both sides of this biogeographic barrier. Our results support emerging evidence that island systems, particularly the geologically complex archipelagoes of the Indo-pacific, are drivers of species diversification. [Historical biogeography; island biogeography; Melanesia; molecular phylogenetics; state-dependent diversification and extinction.].

Systematics and biogeography of the whistlers (Aves: Pachycephalidae) inferred from ultraconserved elements and ancestral area reconstruction.

The utility of islands as natural laboratories of evolution is exemplified in the patterns of differentiation in widespread, phenotypically variable lineages. The whistlers (Aves: Pachycephalidae) are one of the most complex avian radiations, with a combination of widespread and locally endemic taxa spanning the vast archipelagos of the Indo-Pacific, making them an ideal group to study patterns and processes of diversification on islands. Here, we present a robust, species-level phylogeny of all five genera and 85% of species within Pachycephalidae, based on thousands of ultraconserved elements (UCEs) generated with a target-capture approach and high-throughput sequencing. We clarify phylogenetic relationships within Pachycephala and report on divergence timing and ancestral range estimation. We explored multiple biogeographic coding schemes that incorporated geological uncertainty in this complex region. The biogeographic origin of this group was difficult to discern, likely owing to aspects of dynamic Earth history in the Indo-Pacific. The Australo-Papuan region was the likely origin of crown-group whistlers, but the specific ancestral area could not be identified more precisely than Australia or New Guinea, and Wallacea may have played a larger role than previously realized in the evolutionary history of whistlers. Multiple independent colonizations of island archipelagos across Melanesia, Wallacea, and the Philippines contributed to the relatively high species richness of extant whistlers. This work refines our understanding of one of the regions' most celebrated bird lineages and adds to our growing knowledge about the patterns and processes of diversification in the Indo-Pacific.

Population connectivity across a highly fragmented distribution: Phylogeography of the Chalcophaps doves.

Chalcophaps is a morphologically conserved genus of ground-walking doves distributed from India to mainland China, south to Australia, and across the western Pacific to Vanuatu. Here, we reconstruct the evolutionary history of this genus using DNA sequence data from two nuclear genes and one mitochondrial gene, sampled from throughout the geographic range of Chalcophaps. We find support for three major evolutionary lineages in our phylogenetic reconstruction, each corresponding to the three currently recognized Chalcophaps species. Despite this general concordance, we identify discordant mitochondrial and nuclear ancestries in the subspecies C. longirostris timorensis, raising further questions about the evolutionary history of this Timor endemic population. Within each of the three species, we find evidence for isolation by distance or hierarchical population structure, indicating an important role for geography in the diversification of this genus. Despite being distributed broadly across a highly fragmented geographic region known as a hotspot for avian diversification, the Chalcophaps doves show modest levels of phenotypic and genetic diversity, a pattern potentially explained by strong population connectivity owing to high overwater dispersal capability.

A phylogeny of white-eyes based on ultraconserved elements.

White-eyes are an iconic radiation of passerine birds that have been the subject of studies in evolutionary biology, biogeography, and speciation theory. Zosterops white-eyes in particular are thought to have radiated rapidly across continental and insular regions of the Afro- and Indo-Pacific tropics, yet their phylogenetic history remains equivocal. Here, we sampled 77% of the genera and 47% of known white-eye species and sequenced thousands of ultraconserved elements to infer the phylogeny of the avian family Zosteropidae. We used concatenated maximum likelihood and species tree methods and found strong support for seven clades of white-eyes and three clades within the species-rich Zosterops radiation.

Accelerated Brain Shape Evolution Is Associated with Rapid Diversification in an Avian Radiation.

AbstractNiche expansion is a critical step in the speciation process. Large brains linked to improved cognitive ability may enable species to expand their niches and forage in new ways, thereby promoting speciation. Despite considerable work on ecological divergence in brain size and its importance in speciation, relatively little is known about how brain shape relates to behavioral, ecological, and taxonomic diversity at macroevolutionary scales. This is due in part to inherent challenges with quantifying brain shape across many species. Here we present a novel, semiautomated approach for rapidly phenotyping brain shape using semilandmarks derived from X-ray computed microtomography scans. We then test its utility by parsing evolutionary trends within a diverse radiation of birds: kingfishers (Aves: Alcedinidae). Multivariate comparative analyses reveal that rates of brain shape evolution (but not beak shape) are positively correlated with lineage diversification rates. Distinct brain shapes are further associated with changes in body size and foraging behavior, suggesting both allometric and ecological constraints on brain shape evolution. These results are in line with the idea of brains acting as a "master regulator" of critical processes governing speciation, such as dispersal, foraging behavior, and dietary niche.

Complex histories of gene flow and a mitochondrial capture event in a nonsister pair of birds.

Hybridization, introgression, and reciprocal gene flow during speciation, specifically the generation of mitonuclear discordance, are increasingly observed as parts of the speciation process. Genomic approaches provide insight into where, when, and how adaptation operates during and after speciation and can measure historical and modern introgression. Whether adaptive or neutral in origin, hybridization can cause mitonuclear discordance by placing the mitochondrial genome of one species (or population) in the nuclear background of another species. The latter, introgressed species may eventually have its own mtDNA replaced or "captured" by other species across its entire geographical range. Intermediate stages in the capture process should be observable. Two nonsister species of Australasian monarch-flycatchers, Spectacled Monarch (Symposiachrus trivirgatus) mostly of Australia and Indonesia and Spot-winged Monarch (S. guttula) of New Guinea, present an opportunity to observe this process. We analysed thousands of single nucleotide polymorphisms (SNPs) derived from ultraconserved elements of all subspecies of both species. Mitochondrial DNA sequences of Australian populations of S. trivirgatus form two paraphyletic clades, one being sister to and presumably introgressed by S. guttula despite little nuclear signal of introgression. Population genetic analyses (e.g., tests for modern and historical gene flow and selection) support at least one historical gene flow event between S. guttula and Australian S. trivirgatus. We also uncovered introgression from the Maluku Islands subspecies of S. trivirgatus into an island population of S. guttula, resulting in apparent nuclear paraphyly. We find that neutral demographic processes, not adaptive introgression, are the most likely cause of these complex population histories. We suggest that a Pleistocene extinction of S. guttula from mainland Australia resulted from range expansion by S. trivirgatus.

Fine needle aspiration of an intranodal follicular dendritic cell sarcoma: A case report with molecular analysis and review of the literature.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm of follicular dendritic cell origin which can present a diagnostic challenge. Due to the rarity of this neoplasm, its molecular pathogenesis has not been fully elaborated. A previous series of 13 cases reported that 38% contained mutations of genes encoding proteins involved in negative regulation of NF-κB. NF-κB is a family of transcription factors regulated through multiple cellular processes known as the canonical and noncanonical pathways. Here we present the case of a 62-year-old man who presented with abdominal pain and systemic symptoms and was found to have a mass in the porta hepatis. Fine needle aspiration cytology demonstrated a spindle cell neoplasm with vesicular chromatin and prominent nucleoli with admixed lymphocytes. Surgical resection showed an intranodal, 7.3 × 5.5 × 3.5 cm, solid mass composed of plump, spindle to histiocytoid cells with ovoid nuclei and small, prominent nucleoli arranged in a whorled and fascicular pattern. The lesional cells stained positively for CD21, CD23, and CD35 by immunohistochemistry, consistent with a diagnosis of FDCS. Next-generation sequencing revealed pathologic mutations in three genes involved in NF-κB regulation pathways: NFKBIA, TNFAIP3, and TRAF3. A pathologic TP53 mutation was also identified. This case report supports prior associations of the NF-κB pathway dysregulation and FDCS. Additionally, it is the first reported FDCS case with TRAF3 mutation as well as the first reported case to suggest disruption in both the canonical and noncanonical NF-κB pathways in the same lesion.

A large-scale internal validation study of unsupervised virtual trichrome staining technologies on nonalcoholic steatohepatitis liver biopsies.

Non-alcoholic steatohepatitis (NASH) is a fatty liver disease characterized by accumulation of fat in hepatocytes with concurrent inflammation and is associated with morbidity, cirrhosis and liver failure. After extraction of a liver core biopsy, tissue sections are stained with hematoxylin and eosin (H&E) to grade NASH activity, and stained with trichrome to stage fibrosis. Methods to computationally transform one stain into another on digital whole slide images (WSI) can lessen the need for additional physical staining besides H&E, reducing personnel, equipment, and time costs. Generative adversarial networks (GAN) have shown promise for virtual staining of tissue. We conducted a large-scale validation study of the viability of GANs for H&E to trichrome conversion on WSI (n = 574). Pathologists were largely unable to distinguish real images from virtual/synthetic images given a set of twelve Turing Tests. We report high correlation between staging of real and virtual stains ([Formula: see text]; 95% CI: 0.84-0.88). Stages assigned to both virtual and real stains correlated similarly with a number of clinical biomarkers and progression to End Stage Liver Disease (Hazard Ratio HR = 2.06, 95% CI: 1.36-3.12, p < 0.001 for real stains; HR = 2.02, 95% CI: 1.40-2.92, p < 0.001 for virtual stains). Our results demonstrate that virtual trichrome technologies may offer a software solution that can be employed in the clinical setting as a diagnostic decision aid.

Inter- and intra-archipelago dynamics of population structure and gene flow in a Polynesian bird.

Islands are separated by natural barriers that prevent gene flow between terrestrial populations and promote allopatric diversification. Birds in the South Pacific are an excellent model to explore the interplay between isolation and gene flow due to the region's numerous archipelagos and well-characterized avian communities. The wattled honeyeater complex (Foulehaio spp.) comprises three allopatric species that are widespread and common across Fiji, Tonga, Samoa, and Wallis and Futuna. Here, we explored patterns of diversification within and among these lineages using genomic and morphometric data. We found support for three clades of Foulehaio corresponding to three recognized species. Within F. carunculatus, population genetic analyses identified nine major lineages, most of which were composed of sub-lineages that aligned nearly perfectly to individual island populations. Despite genetic structure and great geographic distance between populations, we found low levels of gene flow between populations in adjacent archipelagos. Additionally, body size of F. carunculatus varied randomly with respect to evolutionary history (as Ernst Mayr predicted), but correlated negatively with island size, consistent with the island rule. Our findings support a hypothesis that widespread taxa can show population structure between immediately adjacent islands, and likely represent many independent lineages loosely connected by gene flow.

Fecal Calprotectin Is Highly Effective to Detect Endoscopic Ulcerations in Crohn's Disease Regardless of Disease Location.

BACKGROUND: As the reliability of fecal calprotectin (Fcal) remains debatable to detect endoscopic ulcerations in patients with pure ileal Crohn's disease (CD), we aimed to compare its performances with those observed in patients with colonic or ileocolonic location. METHODS: Using a prospectively maintained database, we analyzed 123 CD patients with Fcal measurement and ileocolonoscopy performed within 1 month with no therapeutic intervention during this interval. Receiver operating characterstic curves (ROC) were used to determine the best Fcal threshold to detect endoscopic ulcerations, taking into account the clinical relevance and usual recommended indices. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were presented with 95% confidence intervals. RESULTS: The mean Fcal level was significantly higher in patients with endoscopic ulcerations in the L1 group (P = 0.025) and the L2-L3 group (P < 0.001). Using ROC curves, Fcal >200 µg/g and Fcal >250 µg/g were the best thresholds to detect endoscopic ulcerations in the L1 group (sensitivity = 75.0, 95% CI, 47.6-92.7; specificity = 87.5, 95% CI, 67.6-97.3; PPV = 80.0, 95% CI, 51.9-95.7; and NPV = 84.0; 95% CI, 63.9-95.5) and in the L2-L3 group (sensitivity = 84.1 95% CI, 69.9-93.4; specificity = 74.4, 95% CI, 57.9-87.0; PPV = 78.7, 95% CI, 64.3-89.3, and NPV = 80.6, 95% CI, 64.0-91.8), respectively. We compared the AUC between L1 and L2-L3 groups, and no difference was shown (0.89 vs 0.84, respectively, P = 0.46). We also compared 2-by-2 sensitivity, specificity, PPV, NPV, and accuracy and we did not observe any significant difference. CONCLUSION: Fecal calprotectin is highly effective to detect endoscopic ulcerations regardless of CD location but requires a lower cutoff value in patients with pure ileal involvement.