The Asymmetry Within: A Renewed Look at Cupids Bow in Unilateral Cleft Lip.

The purpose of this study is to analyze the angular variations within Cupid's bow in patients with unoperated unilateral cleft lip (UCL). Angular features of Cupid's bow were quantified in standardized presurgical photographs of children with UCL by 5 medical professionals specializing in craniofacial anomalies. The peaks and valley of Cupid's bow were identified. A cleft side (CSA) and a noncleft side angle (NCSA) were delineated and measured by each expert. The data was pooled, and the angles were analyzed for symmetry. Cupid's bow asymmetry was defined as a difference between NCSA and CSA ≥3°. Of the 37 patients studied, 29 were found to have asymmetry of Cupid's bow with an average angle difference of 8.0° (95% CI: 6.6°-9.5°). Within this group,15 patients were found with acute asymmetry and 14 with obtuse asymmetry. Geometric analysis was performed on an example of a patient with acute asymmetry to demonstrate how correction of asymmetry can be considered during surgical repair. There is an asymmetry that exists in the Cupid's bow of a significant number of patients with unoperated UCL. This finding not only adds to our understanding of UCL but may also have important implications when selecting the method/technique of surgical repair.

Thrombosis Rates and Genetic Thrombophilia Risk Among Patients With Advanced Germ Cell Tumors Treated With Chemotherapy.

INTRODUCTION: Men with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). Predictors of VTE may identify patients who would benefit from prophylactic anticoagulation. PATIENTS AND METHODS: Men with advanced GCT (Stage IS, II, III) treated with chemotherapy were identified at 2 centers. High genomic risk was defined from a 5 single nucleotide polymorphism (SNP) germline panel. Logistic regression was used to evaluate the impact of genomic risk on VTE within 6 months of chemotherapy initiation. Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA) was used to build models to predict VTE based on clinical variables and an 86 SNP panel. RESULTS: This 123-patient cohort experienced a VTE rate of 26% with an incidence of high genomic risk of 21%. Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5-3.5, P = .54). Incorporation of clinical variables (Khorana score, N3 status and elevated LDH) resulted in adjusted OR 2.1 (95% CI 0.7-6.5, P = .18). A combined model using clinical variables and 86 SNPs performed similarly (AUC 0.77) compared to clinical variables alone (AUC 0.72). CONCLUSIONS: A previously established 5-SNP panel was not associated with VTE among patients with GCT receiving chemotherapy. However, multivariable models based on clinical variables alone warrant further validation to inform prophylactic anticoagulation strategies.

68 Ga-DOTATATE and 18 F-FDG PET Imaging of a Rare Chordoid Meningioma With Intracranial Recurrence and Extracranial Metastases.

ABSTRACT: Chordoid meningiomas, rare meningioma variants, are characterized by their histopathological features and clinical behavior resembling that of other chondroid/myxoid neoplasms. We present a case of pathology-proven chordoid meningioma imaged with both 68 Ga-DOTATATE and 18 F-FDG PET images during a complicated postoperative course with multiple episodes of local recurrence and, ultimately, extracranial metastasis. This case underscores the aggressive behavior of chordoid meningiomas while highlighting how molecular imaging plays an important role in clinical monitoring and guidance of management.

Long-term outcomes after terminalization for acute fingertip injuries.

The primary aim of this study was to report outcomes after fingertip terminalization in 90 patients over a 19-year period. We report excellent functional outcomes and satisfaction, but a 33% incidence of neuropathic pain.

Sequential bilateral total ankle replacements: No difference in patient-reported outcomes between the first and second ankle.

BACKGROUND: Total ankle replacement is an established treatment for end-stage arthritis. However, there is little data examining outcomes in sequential bilateral replacements. This study aimed to compare outcomes between first and second ankles in sequential replacement. METHODS: Patients were retrospectively contacted to complete a follow-up questionnaire including the Manchester-Oxford Foot Questionnaire (MOXFQ), EQ-5D-3 L, and a question assessing satisfaction. Electronic records identified demographics, procedural details, and complications. RESULTS: Twenty patients underwent sequential bilateral ankle replacement over the study period. At a mean follow-up of four years, 18 patients completed the follow-up questionnaire. There was no statistically significant difference between first and second ankles in terms of MOXFQ score, EQ-5D-3 L or satisfaction. Eleven complications were noted. CONCLUSIONS: We report excellent outcomes after sequential bilateral ankle replacement with no difference in outcomes between first and second ankles. These results can be used to counsel patients in the future and manage expectations. LEVEL OF EVIDENCE: IV.

Newly formed dust within the circumstellar environment of SN Ia-CSM 2018evt.

Dust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta-circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line. Our model suggests enhanced CSM dust concentration at increasing distances from the SN as compared to what can be expected from the density profile of the mass loss from a steady stellar wind. By the time of the last mid-infrared observations at day +1,041, a total amount of 1.2 ± 0.2 × 10-2 M⊙ of new dust has been formed by SN 2018evt, making SN 2018evt one of the most prolific dust factories among supernovae with evidence of dust formation. The unprecedented witness of the intense production procedure of dust may shed light on the perceptions of dust formation in cosmic history.

The burden of acute eye conditions on different healthcare providers: a retrospective population-based study.

BACKGROUND: The demand for acute eyecare exponentially outstrips capacity. The public lacks awareness of community eyecare services. AIM: To quantify the burden of acute eyecare on different healthcare service providers in a national population through prescribing and medicines provision by GPs, optometrists, and pharmacists, and provision of care by accident and emergency (A&E) services. A secondary aim was to characterise some of the drivers of this burden. DESIGN AND SETTING: A retrospective data-linkage study set in Wales, UK. METHOD: Analysis of datasets was undertaken from the Secure Anonymised Information Linkage Databank (GP and A&E), the Eye Health Examination Wales service (optometry), and the Common Ailments Scheme (pharmacy) during 2017-2018. RESULTS: A total of 173 999 acute eyecare episodes delivered by GPs (168 877 episodes) and A&E services (5122) were identified during the study. This resulted in 65.4 episodes of care per 1000 people per year. GPs prescribed a total of 87 973 653 prescriptions within the general population. Of these, 820 693 were related to acute eyecare, resulting in a prescribing rate of 0.9%. A total of 5122 eye-related and 905 224 general A&E attendances were identified, respectively, resulting in an A&E attendance rate of 0.6%. Optometrists and pharmacists managed 51.8% (116 868) and 0.6% (2635) of all episodes, respectively. Older females and infants of both sexes were more likely to use GP prescribing services, while adolescent and middle-aged males were more likely to visit A&E. GP prescribing burden was driven partially by economic deprivation, access to services, and health score. Season, day of the week, and time of day were predictors of burden in GP and A&E. CONCLUSION: Acute eyecare continues to place considerable burden on GP and A&E services in Wales, particularly in urban areas with greater economic deprivation and lower overall health. This is likely to increase with a rapidly ageing population. With ongoing pathway development to better utilise optometry and pharmacy, and improved public awareness, there may be scope to change this trajectory.

Impact of primary care triage using the Head and Neck Cancer Risk Calculator version 2 on tertiary head and neck services in the post-coronavirus disease 2019 period.

OBJECTIVE: This study investigates the impact of primary care utilisation of a symptom-based head and neck cancer risk calculator (Head and Neck Cancer Risk Calculator version 2) in the post-coronavirus disease 2019 period on the number of primary care referrals and cancer diagnoses. METHODS: The number of referrals from April 2019 to August 2019 and from April 2020 to July 2020 (pre-calculator) was compared with the number from the period January 2021 to August 2022 (post-calculator) using the chi-square test. The patients' characteristics, referral urgency, triage outcome, Head and Neck Cancer Risk Calculator version 2 score and cancer diagnosis were recorded. RESULTS: In total, 1110 referrals from the pre-calculator period were compared with 1559 from the post-calculator period. Patient characteristics were comparable for both cohorts. More patients were referred on the cancer pathway in the post-calculator cohort (pre-calculator patients 51.1 per cent vs post-calculator 64.0 per cent). The cancer diagnosis rate increased from 2.7 per cent in the pre-calculator cohort to 3.3 per cent in the post-calculator cohort. A lower rate of cancer diagnosis in the non-cancer pathway occurred in the cohort managed using the Head and Neck Cancer Risk Calculator version 2 (10 per cent vs 23 per cent, p = 0.10). CONCLUSION: Head and Neck Cancer Risk Calculator version 2 demonstrated high sensitivity in cancer diagnosis. Further studies are required to improve the predictive strength of the calculator.

PFAS Exposures and the Human Metabolome: A Systematic Review of Epidemiological Studies.

Purpose of Review: There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In this systematic review, we aimed to identify consistent findings between PFAS and metabolomic signatures. We conducted a search matching specific keywords that was independently reviewed by two authors on two databases (EMBASE and PubMed) from their inception through July 19, 2022 following PRISMA guidelines. Recent Findings: We identified a total of 28 eligible observational studies that evaluated the associations between 31 different PFAS exposures and metabolomics in humans. The most common exposure evaluated was legacy long-chain PFAS. Population sample sizes ranged from 40 to 1,105 participants at different stages across the lifespan. A total of 19 studies used a non-targeted metabolomics approach, 7 used targeted approaches, and 2 included both. The majority of studies were cross-sectional (n = 25), including four with prospective analyses of PFAS measured prior to metabolomics. Summary: Most frequently reported associations across studies were observed between PFAS and amino acids, fatty acids, glycerophospholipids, glycerolipids, phosphosphingolipids, bile acids, ceramides, purines, and acylcarnitines. Corresponding metabolic pathways were also altered, including lipid, amino acid, carbohydrate, nucleotide, energy metabolism, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. We found consistent evidence across studies indicating PFAS-induced alterations in lipid and amino acid metabolites, which may be involved in energy and cell membrane disruption.

Addressing barriers to increased adoption of DPYD genotyping at a large multisite cancer center.

PURPOSE: To describe the implementation of an in-house genotyping program to detect genetic variants linked to impaired dihydropyrimidine dehydrogenase (DPD) metabolism at a large multisite cancer center, including barriers to implementation and mechanisms to overcome barriers to facilitate test adoption. SUMMARY: Fluoropyrimidines, including fluorouracil and capecitabine, are commonly used chemotherapy agents in the treatment of solid tumors, such as gastrointestinal cancers. DPD is encoded by the DPYD gene, and individuals classified as DPYD intermediate and poor metabolizers due to certain genetic variations in DPYD can experience reduced fluoropyrimidine clearance and an increased risk of fluoropyrimidine-related adverse events. Although pharmacogenomic guidelines provide evidence-based recommendations for DPYD genotype-guided dosing, testing has not been widely adopted in the United States for numerous reasons, including limited education/awareness of clinical utility, lack of testing recommendations by oncology professional organizations, testing cost, lack of accessibility to a comprehensive in-house test and service, and prolonged test turnaround time. Based on stakeholder feedback regarding barriers to testing, we developed an in-house DPYD test and workflow to facilitate testing in multiple clinic locations at Levine Cancer Institute. Across 2 gastrointestinal oncology clinics from March 2020 through June 2022, 137 patients were genotyped, and 13 (9.5%) of those patients were heterozygous for a variant and identified as DPYD intermediate metabolizers. CONCLUSION: Implementation of DPYD genotyping at a multisite cancer center was feasible due to operationalization of workflows to overcome traditional barriers to testing and engagement from all stakeholders, including physicians, pharmacists, nurses, and laboratory personnel. Future directions to scale and sustain testing in all patients receiving a fluoropyrimidine across all Levine Cancer Institute locations include electronic medical record integration (eg, interruptive alerts), establishment of a billing infrastructure, and further refinement of workflows to improve the rate of pretreatment testing.

A radio-detected type Ia supernova with helium-rich circumstellar material.

Type Ia supernovae (SNe Ia) are thermonuclear explosions of degenerate white dwarf stars destabilized by mass accretion from a companion star1, but the nature of their progenitors remains poorly understood. A way to discriminate between progenitor systems is through radio observations; a non-degenerate companion star is expected to lose material through winds2 or binary interaction3 before explosion, and the supernova ejecta crashing into this nearby circumstellar material should result in radio synchrotron emission. However, despite extensive efforts, no type Ia supernova (SN Ia) has ever been detected at radio wavelengths, which suggests a clean environment and a companion star that is itself a degenerate white dwarf star4,5. Here we report on the study of SN 2020eyj, a SN Ia showing helium-rich circumstellar material, as demonstrated by its spectral features, infrared emission and, for the first time in a SN Ia to our knowledge, a radio counterpart. On the basis of our modelling, we conclude that the circumstellar material probably originates from a single-degenerate binary system in which a white dwarf accretes material from a helium donor star, an often proposed formation channel for SNe Ia (refs. 6,7). We describe how comprehensive radio follow-up of SN 2020eyj-like SNe Ia can improve the constraints on their progenitor systems.

A machine learning algorithm to predict a culprit lesion after out of hospital cardiac arrest.

BACKGROUND: We aimed to develop a machine learning algorithm to predict the presence of a culprit lesion in patients with out-of-hospital cardiac arrest (OHCA). METHODS: We used the King's Out-of-Hospital Cardiac Arrest Registry, a retrospective cohort of 398 patients admitted to King's College Hospital between May 2012 and December 2017. The primary outcome was the presence of a culprit coronary artery lesion, for which a gradient boosting model was optimized to predict. The algorithm was then validated in two independent European cohorts comprising 568 patients. RESULTS: A culprit lesion was observed in 209/309 (67.4%) patients receiving early coronary angiography in the development, and 199/293 (67.9%) in the Ljubljana and 102/132 (61.1%) in the Bristol validation cohorts, respectively. The algorithm, which is presented as a web application, incorporates nine variables including age, a localizing feature on electrocardiogram (ECG) (≥2 mm of ST change in contiguous leads), regional wall motion abnormality, history of vascular disease and initial shockable rhythm. This model had an area under the curve (AUC) of 0.89 in the development and 0.83/0.81 in the validation cohorts with good calibration and outperforms the current gold standard-ECG alone (AUC: 0.69/0.67/0/67). CONCLUSIONS: A novel simple machine learning-derived algorithm can be applied to patients with OHCA, to predict a culprit coronary artery disease lesion with high accuracy.

Neotropical Clavulina: Two new species from Mexico and a re-evaluation of Clavulina floridana.

Clavulina comprises ca. 90 described species distributed worldwide in both tropical and temperate regions. However, only one species (C. floridana) has been described so far from tropical North America. We used morphological and molecular data from three DNA loci (nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 [ITS], a portion of nuc 28S rDNA [28S], and a fragment of DNA-directed RNA polymerase II second largest subunit [RPB2]) from basidiomata and ectomycorrhizas collected in tropical ecosystems from three biogeographic provinces of Mexico and one tropical province in the USA to investigate the phylogenetic and taxonomic diversity of Clavulina in the region. Nine new species-level clades were discovered, two of which are proposed as new species (C. arboreiparva and C. tuxtlasana). Specimens of C. floridana recently collected in Florida were included in our analyses, for which a modern description is provided. In addition, C. floridana is a new record for Mexico. The diversity of Clavulina in tropical North America is comparable to that found in lowland tropical South America. However, some of the species found in tropical deciduous forests produce small, rare, and inconspicuous basidiomata, which easily go unnoticed, and therefore are poorly represented in collections. Many species remain undescribed in tropical regions of North America.

Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022.

BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.

Transsplenic Portal System Catheterization: Review of Current Indications and Techniques.

Multiple diseases of the portal system require effective portal vein access for endovascular management. While percutaneous transhepatic and transjugular approaches remain the standard methods of portal vein access, transsplenic access (TSA) has gained recognition as an effective and safe technique to access the portal system in patients with contraindications to traditional approaches. Recently, the utility of percutaneous TSA has grown, with described treatments including recanalization of chronic portal vein occlusion, placement of stents for portal vein stenosis, portal vein embolization of the liver, embolization of gastric varices, placement of complicated transjugular intrahepatic portosystemic shunts, and interventions after liver transplant. The authors provide a review of percutaneous TSA, including indications, a summary of related portal vein diseases, and the different techniques used for access and closure. In addition, an imaging-based review of technical considerations of TSA interventions is presented, with a review of potential procedural complications. With technical success rates that mirror or rival the standard methods and reported low rates of major complications, TSA can be a safe and effective option in clinical scenarios where traditional approaches are not feasible. ©RSNA, 2022.

Integrative interactomics applied to bovine fescue toxicosis.

Bovine fescue toxicosis (FT) is caused by grazing ergot alkaloid-producing endophyte (Epichloë coenophiala)-infected tall fescue. Endophyte's effects on the animal's microbiota and metabolism were investigated recently, but its effects in planta or on the plant-animal interactions have not been considered. We examined multi-compartment microbiota-metabolome perturbations using multi-'omics (16S and ITS2 sequencing, plus untargeted metabolomics) in Angus steers grazing non-toxic (Max-Q) or toxic (E+) tall fescue for 28 days and in E+ plants. E+ altered the plant/animal microbiota, decreasing most ruminal fungi, with mixed effects on rumen bacteria and fecal microbiota. Metabolic perturbations occurred in all matrices, with some plant-animal overlap (e.g., Vitamin B6 metabolism). Integrative interactomics revealed unique E+ network constituents. Only E+ had ruminal solids OTUs within the network and fecal fungal OTUs in E+ had unique taxa (e.g., Anaeromyces). Three E+-unique urinary metabolites that could be potential biomarkers of FT and targeted therapeutically were identified.

Identification of Acute Mesenteric Ischemia on 18F-FDG PET/CT.

ABSTRACT: Acute mesenteric ischemia resulting in bowel necrosis is a surgical emergency. First identification of acute mesenteric ischemia with FDG PET/CT is uncommon, because patients with bowel ischemia are usually diagnosed by other imaging methods such as CT. Nevertheless, prompt imager recognition of the PET/CT findings of mesenteric ischemia and necrosis is critical for proper triage of the patient to potentially lifesaving interventions. We present a 39-year-old woman with portal vein thrombosis who was sent for 18F-FDG PET/CT evaluation of a suspected pancreatic head neoplasm but was unexpectedly found to have ischemic and necrotic small bowel secondary to mesenteric venous infarction.

Swallow-induced syncope after magnetic sphincter augmentation: a case report and physiologic explanation.

Swallow-induced syncope is a rare cause of syncope that occurs during or immediately after swallowing. This phenomenon has been reported in association with few esophageal pathologies and the likely explanation is a vagal reflex during deglutition that results in inhibition of the cardiac conduction system. This report describes a case of swallow-induced syncope related to the implantation of a magnetic sphincter augmenting (MSA) device. Two episodes of syncope after food bolus occurred with the device in place and upon removal of the device, the patient had no further episodes of syncope. Vagal stimulation from distention of the esophagus or vagus nerve contact irritation by the implant are the potential explanation for syncope in this patient. Although this is an extremely rare complication of magnetic sphincter device augmentation, it is one that physicians should be cognizant of given the dangers of syncope events.

Analysis of Diffusion Tensor Imaging Data From the UK Biobank Confirms Dosage Effect of 15q11.2 Copy Number Variation on White Matter and Shows Association With Cognition.

BACKGROUND: Copy number variations at the 15q11.2 BP1-BP2 locus are present in 0.5%-1.0% of the population, and the deletion is associated with several neurodevelopmental disorders. Previously, we showed a reciprocal effect of 15q11.2 copy number variation on fractional anisotropy, with widespread increases in deletion carriers. We aim to expand these findings using a larger sample of participants (N = 29,166) and higher resolution imaging and by examining the implications for cognitive performance. METHODS: Diffusion tensor imaging measures from participants with no neurological or psychiatric diagnoses were obtained from the UK Biobank database. We compared 15q11.2 BP1-BP2 deletion (n = 102) and duplication (n = 113) carriers to a large cohort of control individuals with no neuropsychiatric copy number variants (n = 28,951). Additionally, we assessed how changes in white matter mediated the association between carrier status and cognitive performance. RESULTS: Deletion carriers showed increases in fractional anisotropy in the internal capsule and cingulum and decreases in the posterior thalamic radiation compared with both duplication carriers and control subjects (who had intermediate values). Compared with control subjects, deletion carriers had lower scores across cognitive tasks, which were partly influenced by white matter. Reduced fractional anisotropy in the posterior thalamic radiation partially contributed to worse cognitive performance in deletion carriers. CONCLUSIONS: These results, together with our previous findings, provide convergent evidence for an effect of 15q11.2 BP1-BP2 on white matter microstructure, this being more pronounced in deletion carriers. Additionally, changes in white matter were found to partially mediate cognitive ability in deletion carriers, providing a link between white matter changes in 15q11.2 BP1-BP2 carriers and cognitive function.