Anatomical Origin Research Articles

Perinatal Outcomes According to the Type of Prenatally Diagnosed Umbilical-Portal-Systemic Venous Shunt

Background: The abnormal course of the umbilical vein and the absence or displacement of the portal vein or ductus venosus may suggest the presence of other shunts. In recent years, an in utero classification of umbilical-portal-systemic venous shunts (UPSVS) has been introduced. This study aims to report our experience with the prenatal diagnosis of UPSVS and to evaluate the perinatal outcomes of fetuses with different types of UPSVS. Methods: This was a retrospective study of fetuses prenatally diagnosed with UPSVS between January 2005 and September 2020 at Asan Medical Center. UPSVS was prenatally classified into three types according to the anatomical origin of the shunt: type I, umbilical-systemic shunt; type II, ductus venosus-systemic shunt; and type III, portal-systemic shunt. Type III was further divided into two subtypes: type IIIa, intrahepatic shunt; type IIIb, extrahepatic shunt. Postnatal ultrasonography or abdominal computed tomography (CT) was performed to confirm UPSVS. Results: Out of 18 fetuses prenatally diagnosed with UPSVS, four were excluded. All four patients were confirmed to have portal vein variations without a shunt. The median gestational age at the diagnosis of the remaining 14 fetuses was 30.3 weeks (range, 23.1–37.3). The median gestational age at birth was 37.2 weeks (range, 31.0–39.3), and the median birth weight was 2105 g (range, 1350–2870), including nine (64%) who had body weights below the 10th percentile. Eleven patients (79%) had combined anomalies; cardiomegaly and fetal hydrops were observed in eight (57%) and two (14%) patients, respectively. Among the 11 patients who underwent chromosomal analysis, three had abnormal results. Two infants with abnormal karyotypes died. The most common type was type I (8, 57%), followed by type IIIa (4, 29%), type II (1, 7%), and type IIIb (1, 7%). In type I, all but one patient had structural anomalies; five (63%) showed cardiomegaly and five (63%) were associated with growth restriction. Nevertheless, half of the patients survived without major anomalies. In type IIIa, three (75%) patients were associated with growth restriction, but they showed catch-up growth after birth. All patients had mild transient hyperammonemia. One type II patient was associated with cardiomegaly, fetal hydrops, and an abnormal karyotype. One type IIIb patient had multiple anomalies and an abnormal karyotype. No surgical correction was required because of the UPSVS. Conclusions: Prenatal diagnosis of UPSVS is feasible. When an abnormal course of the umbilical or portal vein is detected on the transverse abdominal view, UPSVS should be suspected. UPSVS is commonly associated with structural anomalies, chromosomal anomalies, growth restriction, and cardiomegaly. UPSVS without associated anomalies may have a favorable prognosis. Our study can help predict the prognosis of UPSVS and assist in prenatal counseling.

Canal Transportation and Centring Ratio of Paediatric vs Regular Files in Primary Teeth

BackgroundDuring mechanical preparation of the primary root canal, the original anatomy of the tooth should be preserved and the instrument should be perfectly balanced centrally into the canal space for reducing the probability of canal transportation. The aim of this research was to compare canal transportation and canal centring ability in primary root canals using ProTaper Next (Dentsply Mailfair,), AF baby (Fanta), and Kidzo Elephant (Endostar, Poldent Sp.) files. Materials and methodsEighteen root canals were randomly divided into 3 experimental groups (n = 6 in each group). Instrumentation was performed using ProTaper Next, Fanta AF baby, and Kidzo Elephant files in groups 1, 2, and 3, respectively. During the instrumentation procedure, the irrigation of 2 mL of 1.5% sodium hypochlorite between each file was done, followed by 5 mL of 17% ethylenediaminetetraacetic acid as a final irrigating solution. Cone-beam computed tomography images were obtained before and after instrumentation. Each group was evaluated for transportation and centring ratios. ResultsOn comparing all the tested groups within each root canal level canal transportation, the results revealed a statistically nonsignificant difference in the buccolingual direction (P > 0.05). Meanwhile, in the mesiodistal direction, group 1 showed a statistically highly significant difference compared to groups 2 and 3 at the cervical level (P < .01). However, in both middle and apical root canal levels, there was a statistically nonsignificant difference amongst all groups (P > 0.05). Regarding the centring ability comparison of the 3 groups within each root canal level, there was a statistically nonsignificant difference amongst all groups (P > 0.05) in both buccolingual and mesiodistal directions. ConclusionsThe ProTaper Next regular rotary file and the paediatric rotary files showed no difference in canal transportation and centring ability in the buccolingual direction, while in the mesiodistal direction at the cervical root canal level, the ProTaper Next showed high transportation liability.

Traumatic Great Toe MCL Avulsion in Professional Athlete Treated Surgically with MCL Repair with Suture Tape Augmentation Allowing Rapid Return to Sport

Category: Sports; Midfoot/Forefoot; Trauma Introduction/Purpose: Acute medial collateral ligament (MCL) tears of the great toe metatarsophalangeal joint (MTPJ) are a rare occurrence. There is minimal literature existing regarding both operative and non-operative management of this pathology, also known as 'traumatic bunion' due to its low incidence. The closest analog is a traumatic ulnar collateral ligament (UCL) rupture in the hand (Skier's thumb). Suture anchor repair with an internal brace has proven to be an effective treatment for thumb UCL tears with rapid rehabilitation and early range of motion. This method has not yet been reported in literature for a weightbearing joint such as the hallux MTPJ. We present a case report for a professional surfer with traumatic great toe MCL avulsion with surgical technique allowing rapid return to sport. Methods: We present a case report of a novel technique for this rare traumatic MCL avulsion. Surgical management of the great toe MCL was performed utilizing a pre-loaded interference screw to fixate suture at the MCL origin with suture tape augmentation. A mid-axial medial approach was used with L-shaped capsular flap to expose the MCL. 3-0 braided suture was passed through the proximal avulsed MCL. A drill tunnel was prepared at the MCL origin, and the MCL was repaired to its anatomic origin with an interference screw technique for knotless technique. The interference screw was preloaded with suture tape. The suture tape from the interference screw was passed extra articular and the capsule was repaired. The sutuer tape was then inserted into the MCL insertion on the distal phalanx using a small interference screw and drill tunnel for a suture tape augmentation while the toe was held in neutral MTPJ position. Results: He was made weightbearing as tolerated in a CAM boot post-operatively. Immediate active great toe MTPJ motion was permitted. At 2 weeks post-op, sutures were removed, and he was allowed self-directed passive range of motion of the toe, with continued weightbearing as tolerated in the boot. All restrictions were lifted at 4 weeks for a return to play protocol and the patient resumed surfing immediately at that time. His last follow up appointment was at 3 months post-op, at which time he had resumed full activity, had no deformity recurrence, no pain, and his range of motion was symmetric to the contralateral foot. The patient was able to compete at full activity in a national tournament to continue the professional tour at 3 months post- operatively. Conclusion: This report demonstrates a novel surgical technique for the treatment of a rare traumatic MCL avulsion of the great toe (the 'traumatic bunion'). In this case of great toe MCL repair in a professional surfer, we utilized a knotless technique to repair the MCL to it's anatomic origin and also provide suture tape augmentation to allow rapid rehabilitation. This report demonstrates rapid return to sport, an excellent outcome, easy rehabilitation, and straightforward surgical technique. More research will be needed to demonstrate the success of this technique in a broader population.

Non-Anatomic All-Inside Arthroscopic Anterior Talofibular Ligament Repair with a High Position Anchor Shows Inferior Clinical Outcomes: A 3D-CT Based Analysis in Chronic Ankle Instability Patients

Category: Arthroscopy; Sports Introduction/Purpose: In chronic ankle instability (CAI), it is important to repair the anterior talofibular ligament (ATFL) at the anatomic origin site. However, there are limited reports on the clinical outcomes according to anatomical ATFL repair. The purpose of this study is to compare the clinical outcomes after arthroscopic ATFL repair, according to whether the anchor is fixed at an anatomic position. Methods: We performed a retrospective review of consecutive patients who underwent arthroscopic ATFL repair for CAI and were available for a minimum of 2 years follow-up. The patients were divided into three groups according to the anchor position at the distal fibula on 3-dimensional computer tomography: group A, anatomical arthroscopic ATFL repair; group S, sub- anatomical arthroscopic ATFL repair; and group N, non-anatomical arthroscopic ATFL repair. The pain (visual analogue scale [VAS]) score, foot and ankle outcome score (FAOS), and the Karlsson ankle functional score were measured as subjective outcomes. Posturographic analysis and radiologic evaluation using stress radiographs and axial view magnetic resonance imaging were performed as objective outcomes. Results: Of 96 patients, 16 were excluded based on the exclusion criteria, and 80 were evaluated (group A, n = 24; group S, n = 42; and group N, n = 14). The mean age of the patients was 34.5 years, and the mean follow-up period was 27.4 months. A between-group comparison revealed significant differences in the FAOS, Karlsson score, and fall risk evaluated by posturography at the final follow-up. Post hoc analysis revealed that group A patients showed better clinical scores in the FAOS than group N patients in all five domains (all p &lt; 0.017). Patients in groups A and S showed better Karlsson score and fall risk than those in group N (p = 0.004 and 0.013, respectively). In terms of objective outcomes, patients in groups A and S showed better outcomes in fall risk than those in group N (both p = 0.001). Conclusion: Non-anatomic ATFL repair showed inferior outcomes compared to anatomic ATFL repair. When performing arthroscopic ATFL repair, the anchor should be fixed in the anatomical position to improve prognosis.

SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner

Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Visceral fat cells express more ACE2 and are more susceptible to SARS-CoV-2 infection than their subcutaneous counterparts. SARS-CoV-2 infection leads to inhibition of lipolysis in subcutaneous fat cells, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human fat cells, replicating and altering cell function and viability in a depot- and viral lineage-dependent fashion.

FGFR2 Inhibition in Cholangiocarcinoma.

Biliary tract cancer (BTC) is the second most common primary liver cancer after hepatocellular carcinoma and accounts for 2% of cancer-related deaths. BTCs are classified according to their anatomical origin into intrahepatic (iCCA), perihilar, or distal cholangiocarcinoma, as well as gall bladder carcinoma. While the mutational profiles in these anatomical BTC subtypes overlap to a large extent, iCCA is notable for the high frequency of IDH1/2 mutations (10-22%) and the nearly exclusive occurrence of FGFR2 fusions in 10-15% of patients. In recent years, FGFR2 fusions have become one of the most promising targets for precision oncology targeting BTC, with FGFR inhibitors already approved in Europe and the United States for patients with advanced, pretreated iCCA. While the therapeutic potential of nonfusion alterations is still under debate, it is expected that the field of FGFR2-directed therapies will be subject to rapid further evolution and optimization. The scope of this review is to provide an overview of oncogenic FGFR signaling in iCCA cells and highlight the pathophysiology, diagnostic testing strategies, and therapeutic promises and challenges associated with FGFR2-altered iCCA.

Comparative Evaluation of Root Canal Centering Ability of ProTaper, Mtwo, WaveOne, and Reciproc Using Cone-beam Computed Tomography: In Vitro Study

To compare the centering ability of rotating (ProTaper and Mtwo) and reciprocating (WaveOne and Reciproc) file systems using cone-beam computed tomography (CBCT). Eighty extracted human mandibular molars with curvature within 15-45° were selected and randomly divided into four groups (n = 20): group I (ProTaper), group II (Mtwo), group III (WaveOne), and group IV (Reciproc). The selected teeth were arranged in a template, and pre-instrumentation and post-instrumentation CBCT scans were taken using Kodak Carestream CS 9300 machine. The centering ability was measured in four planes namely, at furcation, 3 mm apical to furcation (coronal), 6 mm apical to furcation (middle), and 3 mm coronal to the apex (apical), wherein dentin thickness was measured from pre- and post-instrumentation CBCT scans and recorded for each canal (mesiobuccal and mesiolingual) separately and statistically analyzed. Mtwo and Reciproc remained better centered followed by WaveOne and least by ProTaper in different-level comparisons. In the mesiodistal dimension (MD) at the 3 mm, 6 mm, and 3 mm apical level, Mtwo and Reciproc showed better centering, meanwhile, in the buccolingual dimension, only in the 3 mm apical level, Mtwo and Reciproc remain better centered. A significant difference was seen between the group and type of canal. Mtwo and Reciproc showed better centered preparation than ProTaper and WaveOne. Significant differences were seen between the groups and types of canal. Root canal instrumentation should maintain the original canal anatomy. The proper enlargement keeping in mind the remaining strength in the tooth structure is essentially decided by how the selected instrument is centered. The alloy used for instrument manufacture and its design (taper, cross-section, and tip) will influence the centered preparation. The type of instrument and the instrumentation techniques should be chosen based on root canal anatomy.

Unified rhombic lip origins of group 3 and group 4 medulloblastoma.

Medulloblastoma, a malignant childhood cerebellar tumour, segregatesmolecularly into biologically distinct subgroups, suggesting that a personalized approach to therapy would be beneficial1. Mouse modelling and cross-species genomics have provided increasing evidence of discrete, subgroup-specific developmental origins2. However, the anatomical and cellular complexity of developing human tissues3-particularly within the rhombic lip germinal zone, which produces all glutamatergic neuronal lineages before internalization into the cerebellar nodulus-makes it difficult to validate previous inferences that were derived from studies in mice. Here we use multi-omics to resolve the origins of medulloblastoma subgroups in the developing human cerebellum. Molecular signatures encoded within a human rhombic-lip-derived lineage trajectory aligned with photoreceptor and unipolar brush cellexpression profiles that aremaintained in group 3 and group 4 medulloblastoma, suggesting a convergent basis. A systematic diagnostic-imaging review of a prospective institutional cohort localized the putative anatomical origins of group 3 and group 4 tumours to the nodulus. Our results connect the molecular and phenotypic features of clinically challenging medulloblastoma subgroups to their unified beginnings in the rhombic lip in the early stages of human development.

Ancient DNA analysis from epoxy resin Biodur®-embedded bones.

For microscopic investigation, archaeological bone samples are often embedded in Biodur® epoxy resin. This study wants to test whether it is possible to extract DNA suitable for PCR amplification from this sample type. For eight individuals a set of samples - each consisting of a Biodur-embedded femur sample, a native femur sample and a control sample of different anatomical origin - were submitted to organic DNA extraction. The extraction success was tested by autosomal short tandem repeat amplification. Seven out of eight Biodur-embedded femur samples revealed successful amplification results. If Biodur-embedded bone material exists from earlier microscopic investigations, our results encourage the use of this sample type as a source for genetic research.

Structural association between heterotopia and cortical lesions visualised with 7 T MRI in patients with focal epilepsy

PurposeTo analyze structural characteristics of malformations of cortical development (MCD) at 7T and 3T MRI. MethodsTwenty-five patients were examined with a 7T MRI-scanner in addition to 3T examinations performed for epilepsy evaluation. 7T sequences included a 3D-T1-weighted (T1w) MPRAGE, 3D-T2w FLAIR, and heavily T2w axial and coronal high-resolution (0.5 × 0.5 × 0.75–1.0 mm3) 2D-TSE sequences. Images were reviewed for 7T MRI imaging characteristics of MCD, visibility and frequency of identified lesions on 7T and on 3T (original reports and second reading). ResultsIn 25 patients 112 lesions were identified (57 gray matter (GM) heterotopia, 37 focal cortical dysplasia (FCD), and 18 other MCD). Imaging characteristics of the 37 FCD were cortical thickening (n = 11); GM-WM border blurring (n = 30); GM signal intensity changes (n = 18); juxtacortical WM signal intensity changes (n = 18); and transmantle WM signal intensity changes (n = 11). None of the 7T MRI sequences was sufficient to detect all types of lesions. Heterotopia were in general isointense to normal GM. Structural associations between 36 heterotopia and overlaying cortex were observed, composed either of a direct connection, vessel-like structures, or GM-like bridges.FCD were mentioned in 30% (11 of 37) of the original reports at 3T, and in 57% (21 of 37) after second reading. FCD connections to subcortical heterotopia were clinically not reported at all. Conclusion7T MRI revealed subtle connections between heterotopia and previous unidentified pathology in overlaying cortex. These findings may be significant for the understanding of the anatomical seizure origin and propagation pathways.

371 Topographical Anatomy of the Annulus of Zinn

Abstract Aim The anatomy and even existence of a common tendinous origin of the extraocular eye muscles, or annulus of Zinn, has widely been debated in anatomical literature. This study explored the anatomical origins of the recti muscles, their course into the orbit and the dural connections of the common tendinous origin with the skull base. Method Twenty orbits of ten adult human cadavers were dissected. The orbital apex and its dural connections were photographed. Histological examination of apical specimens was performed. Results In all cadavers, extraocular muscles were observed to have a common tendinous origin at the orbital apex, continuous with dural connections extending into the skull base. Accessory slips of the medial rectus were observed across all cadavers. Dual heads of the lateral rectus were observed in fourteen orbits of seven cadavers. The origin of the levator palpebrae superioris appeared to be contiguous with the superior rectus at the common tendinous origin in all but one cadaver. Conclusions These results support the existence of a common tendinous origin of the extraocular muscles, that is continuous with the skull base dura. In addition, they support the existence of variations in orbital anatomy including dual or accessory muscle slips of the extraocular muscles.

Micro-Computed Tomography Evaluation of Minimally Invasive Shaping Systems in Mandibular First Molars.

The aim of this study was to compare the shaping ability of a modified ProTaper Next technique (PTNm) with that of TruNatomy (TN) in lower molars mesial curved canals using micro-computed tomography (Micro-CT). Sixty mesial canals of first mandibular molars were randomly assigned between two groups (n = 30). After canal scouting with K-File #10, glide path and shaping were carried out with TN or PTNm systems. The PTNm sequence consists of ProGlider, followed by ProTaper Next X1 and apical finishing with NiTiFlex #25 up to working length (WL) to ensure adequate apical cleaning. Samples were scanned using micro-CT and pre- and post-shaping volumes were matched to analyse geometric parameters: the volume of removed dentin; the difference of canal surface; centroid shift, minimum and maximum root canal diameters; cross-sectional areas; the ratio of diameter ratios (RDR) and the ratio of cross-sectional areas (RA). Measurements were assessed 2 mm from the apex and in relation to the middle and coronal root canal thirds. Data were analysed using ANOVA (p < 0.05). No statistically significant differences were found between the groups for any parameter at each level of analysis, except for RA at the coronal level (p = 0.037). The PTNm system showed the tendency to enlarge more in the coronal portion with a lower centroid shift at apical level compared with TN sequence (p > 0.05). Both PTNm and TN sequences demonstrated similar maintenance of original anatomy during the shaping of lower molar mesial curved canals.

How and when of eyelid reconstruction using autologous transplantation.

Reconstructive surgery of the eyelid after tumor excision, trauma or other causes can be challenging, especially due to the complexities of the anatomic structures and to the necessity of both functional and aesthetic successful outcomes. The aim of this minireview was to investigate the use of tissue transplantation in eyelid reconstruction. Surgical procedures are various, based on the use of both flaps, pedicled or free, and grafts, in order to guarantee adequate tissue reconstruction and blood supply, which are necessary for correct healing. Common techniques normally include the use of local tissues, combining non-vascularized grafts with a vascularized flap for the two lamellae repair, to attempt a reconstruction similar to the original anatomy. When defects are too wide, vast, deep, and complex or when no adjacent healthy tissues are available, distant area tissues need to be recruited as free flaps or grafts and paired with mucosal layer reconstruction. With regards to the anterior lamella, full thickness skin grafts are commonly preferred. With regards to the reconstruction of posterior lamella, there are different graft options, which include conjunctival or tarsoconjunctival, mucosal or palatal or cartilaginous grafts usually combined with local flaps. Free flap transplantation, normally reserved for rare select cases, include the use of the radial forearm and anterolateral flaps combined with mucosal grafts, which are surgical options currently reported in the literature.

In This Issue

Current murine models of myeloproliferative neoplasms (MPN) cannot address how MPN can invade hematopoietic organs from a defined single anatomical origin as observed in patients. Murakami et al. developed an immunocompetent wild-type mouse model of Polycythemia Vera (PV) spreading from a single bone marrow site. PV development was abrogated in mice with splenectomy or lacking carbonic anhydrase 1 (CA1) in mutant hematopoietic progenitors. Increased expression of CA1 was found in CD34+ cells from PV patients, and its pharmacologic inhibition decreased variant allele frequency in colony-forming assays, suggesting CA1 as a potential therapeutic target for PV.See article, p. 285.Approximately every fifth patient with myeloproliferative neoplasms (MPN) harbors a CALR mutation of either type I or type II, which differ in clinical features and outcomes. Ibarra et al. show that type I, but not type II, mutant CALR proteins lose Ca2+ binding, causing Ca2+ depletion from the endoplasmic reticulum and activation of the IRE1α/XBP1 pathway. IRE1α inhibition prevented type I-mutant CALR cell survival in culture and thrombocythemia development in mice. These results identify IRE1α/XBP1 as a potentially targetable dependency specific to type I CALR-mutated MPNs.See article, p. 298.By single-cell DNA, RNA and proteogenomic sequencing of matched patient samples, Guess et al. uncovered three clonal evolution patterns associated with clinical progression from myelodysplastic syndrome (MDS) to secondary acute myeloid leukemia (sAML). The Static pattern, characterized by minimal clonal change, had founding clones with mutations in DNA methylation genes and transitioned to sAML in the absence of further genomic aberrations, suggesting nongenetic evolution. Clonal architecture changed dramatically in Dynamic groups, often involving acquisition of mutations in signaling pathways (Dynamic-S) or progressive structural aberrations along with TP53 mutations (Dynamic-C). Collectively, these findings elucidate the interplay of genetic and nongenetic factors in leukemic transformation.See article, p. 316.To investigate patterns of subclone evolution during progression from myelodysplastic syndrome (MDS) to secondary acute myeloid leukemia (sAML), Menssen et al. sequenced paired MDS and sAML samples from a cohort of patients. Signaling gene mutations were found to occur universally in subclones and undergo complex patterns of clonal evolution, including acquisition, expansion, persistence, and contraction of mutations during progression, with multiple patterns often coexisting in the same patient. The presence of at least one signaling gene mutation at MDS was associated with future progression to sAML in patients with lower risk MDS.See article, p. 330.Nakauchi et al. report the genome-wide landscape of DNA hydroxymethylation (5hmC) in human hematopoietic lineages. The authors map TET2-dependent 5hmC, epigenetic and transcriptional programs matched to competitive advantage, myeloid skewing, and reduced erythroid output in TET2-deficient hematopoietic stem and progenitor cells (HSPC). Vitamin C and azacitidine restore the 5hmC landscape and phenotypes in TET2-mutant HSPCs. These findings offer a comprehensive resource for TET-dependent transcriptional regulation of human hematopoiesis and shed light on the potential mechanisms by which TET deficiency contributes to clonal hematopoiesis and malignancies.See article, p. 346.

Considerations in Critical-Care and Anesthetic Management of Adult Patients Living With Fontan Circulation

The Fontan procedure is a staged palliation for various complex congenital cardiac lesions, including tricuspid atresia, pulmonary atresia, hypoplastic left heart syndrome, and double-inlet left ventricle, all of which involve a functional single-ventricle physiology. The complexity of the patients' original anatomy combined with the anatomic and physiologic consequences of the Fontan circulation creates challenges. Teens and adults living with Fontan palliation will need perioperative support for noncardiac surgery, peripartum management for labour and delivery, interventions related to their structural heart disease, electrophysiology procedures, pacemakers, cardioversions, cardiac surgery, transplantation, and advanced mechanical support. This review focuses on the anesthetic and intensive care unit (ICU) management of these patients during their perioperative journey, with an emphasis on the continuity of preintervention planning, referral pathways, and postintervention ICU management. Requests for recipes and doses of medications are frequent; however, as in normal anesthesia and ICU practice, the method of anesthesia and dosing are dependent on the presenting medical/surgical conditions and the underlying anatomy and physiologic reserve. A patient with Fontan palliation in their early 20s attending school full-time with a cavopulmonary connection is likely to have more reserve than a patient in their late 40s with an atriopulmonary Fontan at home waiting for a heart transplant. Each case will require an anesthetic and critical care plan tailored to the situation. The critical care environment is a natural extension of the anesthetic management of a patient, with complex considerations for a patient with Fontan palliation.

Natural Language Processing Approaches for Retrieval of Clinically Relevant Genomic Information in Cancer.

The accelerating impact of genomic data in clinical decision-making has generated a paradigm shift from treatment based on the anatomic origin of the tumor to the incorporation of key genomic features to guide therapy. Assessing the clinical validity and utility of the genomic background of a patient’s cancer represents one of the emerging challenges in oncology practice, demanding the development of automated platforms for extracting clinically relevant genomic information from medical texts. We developed PubMiner, a natural language processing tool to extract and interpret cancer type, therapy, and genomic information from biomedical abstracts. Our initial focus has been the retrieval of gene names, variants, and negations, where PubMiner performed highly in terms of total recall (91.7%) with a precision of 79.7%. Our next steps include developing a web-based interface to promote personalized treatment based on each tumor’s unique genomic fingerprints.

Frontal Lobe Epilepsy in a Pediatric Population: Characterization of Clinical Manifestations and Semiology

Purpose: Frontal lobe epilepsy (FLE) has various clinical presentations depending on the anatomy involved. Seizures are brief and can mimic psychiatric conditions, and patients often cannot describe the aura. Therefore, it is difficult to characterize the semiology, especially in pediatric patients. This study investigated the characteristics of pediatric FLE.Methods: We retrospectively reviewed the data of pediatric patients with FLE who underwent long-term video-electroencephalography (EEG) monitoring between January 2010 and June 2020. Patients’ demographic data, seizure-related clinical presentations, semiology, brain magnetic resonance imaging (MRI), and EEG data were analyzed.Results: Fifty-six patients were included (31 males, 25 females). The age of seizure onset varied from 1 month to 14 years (mean±standard deviation, 6.1±4.4 years). Seizures were classified into nine categories, including focal tonic (30/56), aura (22/56), hypermotor (17/56), focal clonic (15/56), versive (13/56), and bilateral asymmetric tonic (4/56). Seventeen patients (30.4%) had abnormal MRI results, including focal cortical dysplasia, heterotopic gray matter, and neuroepithelial tumors. Ictal EEG changes were commonly observed in the dorsolateral premotor and central cortices. In focal tonic seizures, EEG changes often originated in the premotor cortex. The location of the lesions on MRI and EEG coincided in six cases.Conclusion: In pediatric FLE, various seizure types occur depending on the ictal anatomic origin, and individual patients had multiple semiologies. Brain MRI was normal in two-thirds of patients, and interictal EEG did not reveal epileptiform discharges in approximately 25%. Semiology reported on the basis of home videos and interictal EEG will help localize the ictal onset zone.

On the Comparison Between the Nc/CRN and the Ne/ERN.

After the Error Negativity (Ne or ERN) has been described on full-blown errors and on partial error, a smaller Error Negativity-like wave (CRN or Nc) has also been evidenced on correct trials, first in patients with schizophrenia and, later on, in healthy subjects. The functional significance of the Nc as compared to the Ne is of critical importance since most models accounting for the genesis of the Ne on errors and partial errors cannot account for the existence of the Nc if this Nc simply corresponds to a small Ne. On the contrary, if the Nc and the Ne are two completely distinct components, then the existence of a Nc poses no constraint to the existing models. To this end, we examine in the present review the similarities and the differences existing between the Ne and the Nc regarding their functional properties and their anatomical origin.

Abstract 2289: Comprehensive multiomic analysis reveals different subtypes in neuroendocrine tumors from multiple origins

Abstract Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with a wide anatomical distribution and different clinical behaviors that share common “neuro” and “endocrine” properties. They are classified in well differentiated G1, G2 and G3 neuroendocrine tumors (NETs), or poorly differentiated neuroendocrine carcinomas (NECs) which are all G3. Some studies have assessed the NET molecular landscape of certain primary sites, but no cross-sites molecular assessment has been performed to date. Thus, we aimed to perform a comprehensive transcriptomic and methylomic characterization of large series of NENs of different anatomical origins in order to identify molecular subgroups, unravel genes and/or pathways involved, and explore their potential clinical relevance. Transcriptomic and methylation data were obtained from tumor samples of 181 and 99 patients with NENs (37.02%G1; 54.7%G2 and 8.29%G3) using Clariom S Human microarrays and EPIC methylation arrays, respectively. Most common primary tumor site was the lung (43.1%), followed by the small intestine (35.4%), large intestine (8.8%), stomach (4.4%), pancreas (1.7%), other localizations (3.9%), and unknown primary (2.8%). Tumors were clustered using transcriptomic and methylation data by NMF and hierarchical clustering algorithms respectively, and differential expression (limma analysis) and gene set enrichment analysis (GSEA) was applied to transcriptomic data clusters NENs were classified into three different clusters. Two of them (C1 and C3) showed an inverse transcriptomic profile, while C2 presented a mixed profile. We identified that C3 had the highest expression levels of neuroendocrine-related genes (somatostatin receptor SSTR5 LFC: 0.77 ; FDR: 1.52x10e-25 ; serotonin receptor HTR1A LFC: 0.79 ; FDR: 1.20X10e-20 ; VIP LFC: 0.64 ; FDR= 1.41x10e-10 etc), in lung primary tumor samples (50%) and methylation cluster 1 (82.14%). On the other hand, C1 was enriched in some important cancer-related pathways ( MYC targets NES -6.37 FDR &amp;lt; 10-3; MTORC1 NES -3.78 FDR &amp;lt; 10-3) and oxidative phosphorylation (NES -4.87 FDR &amp;lt; 10-3) ; and showed a higher proportion of small intestine primary tumors (46.34%), Grade 2 tumors (73.17%) and methylation cluster 2 (75%). NENs of different primary sites can be stratified into two major transcriptomic clusters, with a third cluster having a mixed expression profile. The groups with extreme transcriptomic signatures were enriched in neuroendocrine-related genes or principal cancer pathways. These results suggest a dedifferentiation from a more indolent neuroendocrine phenotype to more aggressive proliferative tumor types that could be driven partially with the methylation profile. Citation Format: Carlos Carretero Puche, Beatriz Soldevilla, Beatriz Gil, Anna La Salvia, Alberto Lens-Pardo, Paula Espinosa, Beatriz Anton-Pascual, Gonzalo Gómez-López, Fátima Al-Shahrour, Rocío García-Carbonero. Comprehensive multiomic analysis reveals different subtypes in neuroendocrine tumors from multiple origins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2289.

EPEN-05. Adenosine receptor expression in paediatric ependymoma

PURPOSE: Paediatric ependymoma is associated with dismal outcomes. Whilst understanding of its underlying biology has advanced, there has been little progress in treatment and clinical outcomes. Acting through four G protein-coupled receptors (encoded by ADORA1, ADORA2A, ADORA2B and ADORA3), adenosine is a signalling molecule often present at high levels in tumours. Adenosine signalling can aid tumour proliferation and invasiveness via mechanisms including suppression of tumour-infiltrating immune cells. Adenosine receptors therefore represent a potential therapeutic target in paediatric ependymoma, however neither levels nor patterns of expression have been previously reported. We hypothesised that adenosine receptors would be expressed in paediatric ependymoma and that this expression would vary between molecular subgroups. METHODS: Three publicly available gene expression datasets were analysed for adenosine receptor expression using Kruskal-Wallis, Mann-Whitney U and chi-square tests. RNAscope assays for adenosine receptors and CD68 were then performed on ten full-face ependymoma FFPE sections from posterior fossa A (PFA1 and PFA2) tumours to understand patterns of expression within ependymomas with the highest levels of expression identified by the gene expression datasets. RESULTS: Statistically significant differences were identified between adenosine-related genes across ependymoma subgroups of differing anatomical origin (supratentorial ZFTA-positive versus posterior fossa A and B (PFA/PFB)), with median adenosine-related gene levels generally higher in the PFA subgroup. Particularly, ADORA1, 2A, 2B and 3 gene expression was higher in PFA tumours than other subgroups. Analysis of the ten cases demonstrated measurable expression of all four adenosine receptors by RNAscope and patterns in the distribution and relative levels of expression of the adenosine receptors across PFA1 and PFA2 tumours were described. CONCLUSION: Using two different techniques we demonstrated that adenosine receptors are expressed in paediatric ependymomas. There are significant differences in level of expression between tumour subgroups. Adenosine receptors therefore represent a potential therapeutic target which should be explored further.