Update from the 5th Edition of the WHO Classification of Nasal, Paranasal, and Skull Base Tumors: Imaging Overview with Histopathologic and Genetic Correlation.

Sinonasal and skull base tumors are a heterogeneous group of neoplasms with considerable histologic variation and overlapping imaging features. In 2022, the World Health Organization updated the head and neck tumor classification, further emphasizing the importance of molecular data and genetic alterations in sinonasal neoplasms. The changes include the addition of new entities and discussion of emerging entities, as well as changes to the taxonomy and characterization of tumors. The new classification focuses on entities that develop in these sites either exclusively (eg, olfactory neuroblastoma) or most frequently. Another change includes reduction in the number of categories by creating separate category-specific chapters for soft-tissue, hematolymphoid, and neuroectodermal lesions. In this review, we briefly discuss the various categories in the new classification with a more detailed description of the 2 new entities (SWItch/Sucrose Non-Fermentable complex-deficient sinonasal carcinomas and human papillomavirus-related multiphenotypic sinonasal carcinoma). We also highlight the emerging entities including IDH-mutant sinonasal malignancies and DEK-AFF2 carcinoma, presently classified as sinonasal undifferentiated carcinoma and nonkeratinizing squamous cell carcinoma, respectively.

Germination of shrub species from Chinese subtropical forests: implications for restoration.

Incorporating native shrubs into restoration projects can improve biodiversity conservation and enhance the sustainability of ecosystem functions. Shrubs grow under different forest canopy structures, having varied microclimatic conditions according to forest type and composition. Currently, there is a lack of information on propagation from seed and planting material availability for the utilization of shrubs in forest restoration. In the present study, we evaluated the effects of temperature and light on germination of ten shrub species (Ardisia japonica, Callicarpa cathayana, Callicarpa giraldii var. subcanescens, Deutzia schneideriana, Fraxinus sieboldiana, Hydrangea chinensis, Maesa japonica, Rhododendron simsii, Spiraea japonica var. fortunei and Weigela japonica var. sinica) occurring in subtropical forests in China. No seeds of any species germinated in the coolest thermal regime (5/10 °C), while optimal temperature requirements varied from 10/20 °C to 25/35 °C. Seeds of small-seeded species had higher germination percentages in the light treatments, while larger seeds were not photoblastic. There was no relationship between germination in the light and the seed shape index. Our results may assist in identification of seed traits and suitable shrub species for restoration in specific forest types, thus aiding native forest recovery of structure and composition. Successful recovery leads to enhanced biodiversity, reestablishment of microhabitats and ecological interactions in the forest understorey.

High-Resolution 7T MR Imaging of the Trochlear Nerve.

BACKGROUND AND PURPOSE: The trochlear nerve has traditionally been difficult to identify on MR imaging. The advent of 7T MR imaging promises to greatly benefit visualization of small structures due to gains in the signal-to-noise ratio allowing improved spatial resolution. We investigated the utility of a clinically feasible ultra-high-resolution 7T MR imaging protocol for identification of the trochlear nerve, as well as assessment of normal trochlear nerve anatomy. MATERIALS AND METHODS: Coronal high-resolution 2D T2-weighted TSE images used in a 7T epilepsy protocol of 50 subjects at our institution were reviewed by 2 independent radiologists for visualization of the trochlear nerve at the nerve origin and cisternal, tentorial, and cavernous segments. The frequency of nerve visibility within these segments and their anatomy were documented, and disagreements were resolved by joint review. RESULTS: Of the 100 nerves reviewed in 50 subjects, at least 2 segments of the trochlear nerve from the brainstem to the cavernous sinus were identified in 100% of cases. The origins from the brainstem and cisternal segment were visible in 65% and 93% of nerves, respectively. The trochlear nerve was identified at the trochlear groove in 100% of cases and in the posterior wall of the cavernous sinus in 74% of cases. CONCLUSIONS: Coronal high-resolution 2D TSE at 7T reliably identified the trochlear nerve throughout its course and is a promising tool for imaging patients with suspected trochlear nerve pathology.

Neck Imaging Reporting and Data System: More Than Just a Template.

The Neck Imaging Reporting and Data System (NI-RADS) is a guide developed and introduced in 2017 by head and neck radiologists who worked in an academic radiology department. Based on the Breast Imaging Reporting and Data System, the initial goals of NI-RADS were to make posttreatment head and neck cancer imaging dictations more succinct and efficient, guide treating physicians in the next appropriate steps when recurrence was suspected, and encourage institutional and national research. NI-RADS is more than a dictation template, and it is best instituted after a head and neck imaging practice is established. We support the use of NI-RADS once a radiologist understands the nuances of head and neck cancer, including the biology, common subsites involved, essentials of tumor staging, common posttreatment benign imaging appearances, and subtleties of recurrent disease.

Brain Abnormalities and Epilepsy in Patients with Parry-Romberg Syndrome.

BACKGROUND AND PURPOSE: Parry-Romberg syndrome is a rare disorder characterized by progressive hemifacial atrophy. Concomitant brain abnormalities have been reported, frequently resulting in epilepsy, but the frequency and spectrum of brain involvement are not well-established. This study aimed to characterize brain abnormalities in Parry-Romberg syndrome and their association with epilepsy. MATERIALS AND METHODS: This is a single-center, retrospective review of patients with a clinical diagnosis of Parry-Romberg syndrome and brain MR imaging. The degree of unilateral hemispheric atrophy, white matter disease, microhemorrhage, and leptomeningeal enhancement was graded as none, mild, moderate, or severe. Other abnormalities were qualitatively reported. Findings were considered potentially Parry-Romberg syndrome-related when occurring asymmetrically on the side affected by Parry-Romberg syndrome. RESULTS: Of 80 patients, 48 (60%) had brain abnormalities identified on MR imaging, with 26 (32%) having abnormalities localized to the side of the hemifacial atrophy. Sixteen (20%) had epilepsy. MR imaging brain abnormalities were more common in the epilepsy group (100% versus 48%, P < .001) and were more frequently present ipsilateral to the hemifacial atrophy in patients with epilepsy (81% versus 20%, P < .001). Asymmetric white matter disease was the predominant finding in patients with (88%) and without (23%) epilepsy. White matter disease and hemispheric atrophy had a higher frequency and severity in patients with epilepsy (P < .001). Microhemorrhage was also more frequent in the epilepsy group (P = .015). CONCLUSIONS: Ipsilateral MR imaging brain abnormalities are common in patients with Parry-Romberg syndrome, with a higher frequency and greater severity in those with epilepsy. The most common findings in both groups are white matter disease and hemispheric atrophy, both presenting with greater severity in patients with epilepsy.

Absence of Meckel Cave: A Rare Cause of Trigeminal Neuralgia.

Trigeminal neuralgia is a debilitating condition with numerous etiologies. In this retrospective case series, we report a cohort of patients with a rarely described entity, absence of Meckel cave, and propose this as a rare cause of trigeminal neuralgia. A search of the electronic medical record was performed between 2000 and 2020 to identify MR imaging reports with terms including "Meckel's cave" and "hypoplasia," "atresia," "collapse," or "asymmetry." Images were reviewed by 2 blinded, board-certified neuroradiologists. Seven cases of the absence of Meckel cave were identified. Seven patients (100%) had ipsilateral trigeminal neuralgia and ipsilateral trigeminal nerve atrophy, suggesting an association between absence of Meckel cave and trigeminal neuralgia. Absence of Meckel cave is a rare entity of unknown etiology, with few existing reports that suggest the possibility of an association with trigeminal neuralgia. Its recognition may have important implications in patient management. Future studies and longitudinal data are needed to assess treatment outcomes and added risks from surgical intervention in these patients.

The Updated Neuroradiology Milestones: Synapsing from 1.0 to 2.0.

The Accreditation Council for Graduate Medical Education is currently in the process of specialty-by-specialty revision of the Milestones. As a result, the Neuroradiology Milestones 2.0 Workgroup was created to refine a system of competency-based assessments for fellow educational growth and development. Strengths of the new Milestones include decreased complexity and uniformity within a subcompetency as it relates to a specific educational development trajectory. The Supplemental Guide serves to decrease clutter in the Milestones 2.0 document and provides a more practical resource for guidance. This article serves to review the history of the Neuroradiology Milestones, followed by a summary of the timeline of events and discussions of the workgroup for development of Neuroradiology Milestones 2.0 and a synopsis of major changes. The plan is for the updated Neuroradiology Milestones to take effect in 2021 or 2022 based on public commentary.

Gut microbiome profiling of a rural and urban South African cohort reveals biomarkers of a population in lifestyle transition.

BACKGROUND: Comparisons of traditional hunter-gatherers and pre-agricultural communities in Africa with urban and suburban Western North American and European cohorts have clearly shown that diet, lifestyle and environment are associated with gut microbiome composition. Yet, little is known about the gut microbiome composition of most communities in the very diverse African continent. South Africa comprises a richly diverse ethnolinguistic population that is experiencing an ongoing epidemiological transition and concurrent spike in the prevalence of obesity, largely attributed to a shift towards more Westernized diets and increasingly inactive lifestyle practices. To characterize the microbiome of African adults living in more mainstream lifestyle settings and investigate associations between the microbiome and obesity, we conducted a pilot study, designed collaboratively with community leaders, in two South African cohorts representative of urban and transitioning rural populations. As the rate of overweight and obesity is particularly high in women, we collected single time-point stool samples from 170 HIV-negative women (51 at Soweto; 119 at Bushbuckridge), performed 16S rRNA gene sequencing on these samples and compared the data to concurrently collected anthropometric data. RESULTS: We found the overall gut microbiome of our cohorts to be reflective of their ongoing epidemiological transition. Specifically, we find that geographical location was more important for sample clustering than lean/obese status and observed a relatively higher abundance of the Melainabacteria, Vampirovibrio, a predatory bacterium, in Bushbuckridge. Also, Prevotella, despite its generally high prevalence in the cohorts, showed an association with obesity. In comparisons with benchmarked datasets representative of non-Western populations, relatively higher abundance values were observed in our dataset for Barnesiella (log2fold change (FC) = 4.5), Alistipes (log2FC = 3.9), Bacteroides (log2FC = 4.2), Parabacteroides (log2FC = 3.1) and Treponema (log2FC = 1.6), with the exception of Prevotella (log2FC = - 4.7). CONCLUSIONS: Altogether, this work identifies putative microbial features associated with host health in a historically understudied community undergoing an epidemiological transition. Furthermore, we note the crucial role of community engagement to the success of a study in an African setting, the importance of more population-specific studies to inform targeted interventions as well as present a basic foundation for future research.

Prospective correlation of the radiological, surgical and pathological findings in patients undergoing cytoreductive surgery for colorectal peritoneal metastases: implications for the preoperative estimation of the peritoneal cancer index.

AIM: The peritoneal cancer index (PCI) is one of the strongest prognostic factors in patients undergoing cytoreductive surgery (CRS) for colorectal peritoneal metastases. Using pathological evaluation, however, the disease extent differs in a large proportion of patients. Our aim was to study the correlation between the radiological (rPCI), surgical (sPCI) and pathological (pPCI) PCI in order to determine factors affecting the discordance between these indices and their potential therapeutic implications. METHOD: From July 2018 to December 2019, 128 patients were included in this study. The radiological, pathological and surgical findings were compared. A protocol for pathological evaluation was followed at all centres. RESULTS: All patients underwent a CT scan and 102 (79.6%) had a peritoneal MRI. The rPCI was the same as the sPCI in 81 (63.2%) patients and the pPCI in 93 (72.6%). Concordance was significantly lower for moderate-volume (sPCI 13-20) and high-volume (sPCI > 20) disease than for low-volume disease (sPCI 0-12) (P < 0.001 for sPCI; P = 0.001 for pPCI). The accuracy of imaging in predicting presence/absence of disease upon pathological evaluation ranged from 63% to 97% in the different regions of the PCI. The pPCI concurred with the sPCI in 86 (68.8%) patients. Of the nine patients with sPCI > 20, the pPCI was less than 20 in six. CONCLUSION: The rPCI and sPCI both concurred with pPCI in approximately two thirds of patients. Preoperative evaluation should focus on the range in which the sPCI lies and not its absolute value. Radiological evaluation did not overestimate sPCI in any patient with high/moderate-volume disease. The benefit of CRS in patients with a high r/sPCI (> 20) who respond to systemic therapies should be prospectively evaluated.

The development of the Clinician-reported Genetic testing Utility InDEx (C-GUIDE): a novel strategy for measuring the clinical utility of genetic testing.

PURPOSE: Clinical utility describes a genetic test's value to patients, families, health-care providers, systems, or society. This study aims to define clinical utility from the perspective of clinicians and develop a novel outcome measure that operationalizes this concept. METHODS: Item selection for the Clinician-reported Genetic testing Utility InDEx (C-GUIDE) was informed by a scoping review of the literature. Item reduction was guided by qualitative and quantitative feedback from semistructured interviews and a cross-sectional survey of genetics and nongenetics specialists. Final item selection, index scoring, and structure were guided by feedback from an expert panel of genetics professionals. RESULTS: A review of 194 publications informed the selection of a preliminary set of 25 items. Feedback from 35 semistructured interviews, 113 surveys, and 11 expert panelists informed the content and wording of C-GUIDE's final set of 18 items that reflect on the utility of testing related to diagnosis, management, and familial/psychosocial impact. C-GUIDE achieves content and face validity for use in a range of diagnostic genetic testing settings. CONCLUSION: Work to establish reliability and construct validity is underway. C-GUIDE will be useful in comparative studies to generate policy-relevant evidence pertaining to the clinical utility of genetic testing across a range of settings.

Patients with extensive regional lymph node involvement (pN2) following potentially curative surgery for colorectal cancer are at increased risk for developing peritoneal metastases: a retrospective single-institution study.

AIM: Our goal was to determine the incidence and clinical behaviour of peritoneal metastases (PM) in patients with colorectal cancer undergoing potentially curative surgery, comparing patients with extensive locoregional lymph node involvement (pN2) with those who have serosal involvement (pT4), a known risk factor for developing PM. METHOD: A retrospective analysis of a prospectively maintained database was performed. All patients with pT4 and pN2 were included in the analysis. The diagnostic criteria were the finding of PM during surgery with biopsy confirmation as well as imaging features suggestive of PM, including ovarian metastases and omental deposits. RESULTS: Two hundred and fourteen patients treated between May 2010 and October 2015 were included. Of these, 110 (51.4%) had pT4 and 131 (61.2%) pN2 tumours: 17.2% of patients with pT4 tumours and 20.2% of patients with pN2 tumours developed PM (P = 0.53). The median time to detection of PM was 16.6 months and 11.8 months for pT4 and pN2 tumours, respectively. PM were isolated in 51.8% of patients with pN2 tumours. Nonperitoneal metastases developed in 37.5% of patients with pN2 tumours. In pN2 tumours, the incidence of PM was higher in signet ring cell and mucinous tumours (P < 0.01), positive surgical margins (P = 0.02), colonic versus rectal tumours (P = < 0.01) and right colon primary tumours (P = 0.01). CONCLUSION: Patients with pN2 tumours are at an increased risk of developing PM, which is similar to the risk in pT4 tumours. pN2 tumours should be included in clinical trials evaluating preventive/proactive strategies. There is a need to identify predictive biomarkers for the development of PM versus other sites of metastasis.

Antibiotic-mediated modification of the intestinal microbiome in allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many patients with severe benign and malignant hematologic disorders. The success of allogeneic HSCT is limited by the development of transplant-related complications such as acute graft-versus-host disease (GvHD). Early pre-clinical studies suggested that intestinal microflora contribute to the pathogenesis of acute GvHD, and that growth suppression or eradication of intestinal bacteria prevented the development of acute GvHD even in MHC-mismatched transplants. These observations led to the practice of gut decontamination (GD) with oral non-absorbable antibiotics in patients undergoing allogeneic HSCT as a method of acute GvHD prophylaxis. Microbiome studies in the modern sequencing era are beginning to challenge the benefit of this practice. In this review, we provide a historical perspective on the practice of GD and highlight findings from the limited number of clinical trials evaluating the use of GD for acute GvHD prevention in allogeneic HSCT patients. In addition, we examine the role of the gut microbiota in allogeneic HSCT in the context of recent studies linking the microflora to regulation of intestinal immune homeostasis. We discuss the implications of these findings for future strategies to reduce acute GvHD risk by selective manipulation of the microbiota.

Stabilizing lithium metal using ionic liquids for long-lived batteries.

Suppressing dendrite formation at lithium metal anodes during cycling is critical for the implementation of future lithium metal-based battery technology. Here we report that it can be achieved via the facile process of immersing the electrodes in ionic liquid electrolytes for a period of time before battery assembly. This creates a durable and lithium ion-permeable solid-electrolyte interphase that allows safe charge-discharge cycling of commercially applicable Li|electrolyte|LiFePO4 batteries for 1,000 cycles with Coulombic efficiencies >99.5%. The tailored solid-electrolyte interphase is prepared using a variety of electrolytes based on the N-propyl-N-methylpyrrolidinium bis(fluorosulfonyl)imide room temperature ionic liquid containing lithium salts. The formation is both time- and lithium salt-dependant, showing dynamic morphology changes, which when optimized prevent dendrite formation and consumption of electrolyte during cycling. This work illustrates that a simple, effective and industrially applicable lithium metal pretreatment process results in a commercially viable cycle life for a lithium metal battery.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined have been recognized as standard of care for treatment of a subset of patients with peritoneal carcinomatosis (PC). The aim of CRS is to eliminate all macroscopic disease through a series of visceral resections followed by targeting any residual microscopic disease with intraperitoneal chemotherapy, exposing the peritoneal surfaces to a high concentration of chemotherapy with a lower systemic toxicity. Different regimes of intraperitoneal chemotherapy include HIPEC, early postoperative intraperitoneal chemotherapy (EPIC) and bidirectional chemotherapy. The efficacy and modality of treatment with intraperitoneal chemotherapy is dependent on multiple factors including the chosen cytotoxic agent and its pharmacokinetics and pharmacodynamics. There is no standardized methodology for intraperitoneal chemotherapy administration. This review will discuss the pharmacological principles of the various intraperitoneal chemotherapy techniques.

Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats.

Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxydopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown by improved locomotor activity, tapered/ledged beam-walking performance, vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8% increase in tyrosine hydroxylase (TH)-positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong neuroprotection in the 6-OHDA rat PD model, suggesting that insulin signaling may be a novel therapeutic target in broad neurodegenerative disorders.

Pilot study of chronic maternal hyperoxygenation and effect on aortic and mitral valve annular dimensions in fetuses with left heart hypoplasia.

OBJECTIVE: Acute maternal hyperoxygenation (AMH) results in increased fetal left heart blood flow. Our aim was to perform a pilot study to determine the safety, feasibility and direction and magnitude of effect of chronic maternal hyperoxygenation (CMH) on mitral and aortic valve annular dimensions in fetuses with left heart hypoplasia (LHH) after CMH. METHODS: Gravidae with fetal LHH were eligible for inclusion in a prospective evaluation of CMH. LHH was defined as: sum of aortic and mitral valve annuli Z-scores < -4.5, arch flow reversal and left-to-right or bidirectional atrial level shunting without hypoplastic left heart syndrome or severe aortic stenosis. Gravidae with an affected fetus and with ≥ 10% increase in aortic/combined cardiac output flow after 10 min of AMH at 8 L/min 100% fraction of inspired oxygen were offered enrollment. Nine gravidae were enrolled from February 2014 to January 2015. The goal therapy was ≥ 8 h daily CMH from enrollment until delivery. Gravidae who were cared for from July 2012 to October 2014 with fetal LHH and no CMH were identified as historical controls (n = 9). Rates of growth in aortic and mitral annuli over the final trimester were compared between groups using longitudinal regression. RESULTS: There were no significant maternal or fetal complications in the CMH cohort. Mean gestational age at study initiation was 29.6 ± 3.2 weeks for the intervention group and 28.4 ± 1.8 weeks for controls (P = 0.35). Mean relative increase in aortic/combined cardiac output after AMH was 35.3% (range, 18.1-47.9%). Median number of hours per day on CMH therapy was 9.3 (range, 6.5-14.6) and median duration of CMH was 48 (range, 33-84) days. Mean mitral annular growth was 0.19 ± 0.05 mm/week compared with 0.14 ± 0.05 mm/week in CMH vs controls (mean difference 0.05 ± 0.05 mm/week, P = 0.33). Mean aortic annular growth was 0.14 ± 0.03 mm/week compared with 0.13 ± 0.03 mm/week in CMH vs controls (mean difference 0.01 ± 0.03 mm/week, P = 0.75). More than 9 h CMH daily (n = 6) was associated with better growth of the aortic annulus in intervention fetuses (0.16 ± 0.03 vs 0.08 ± 0.02 mm/week, P = 0.014). CONCLUSIONS: CMH is both safe and feasible for continued research. In this pilot study, the effect estimates of annular growth, using the studied method of delivery and dose of oxygen, were small. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Reasons why patients fail screening in Indian breast cancer trials.

INTRODUCTION: An increased number of screen failure patients in a clinical trial increases time and cost required for the recruitment. Assessment of reasons for screen failure can help reduce screen failure rates and improve recruitment. MATERIALS AND METHODS: We collected retrospective data of human epidermal growth factor receptor (HER2) positive Indian breast cancer patients, who failed screening for phase 3 clinical trials and ascertained their reasons for screen failure from screening logs. Statistical comparison was done to ascertain if there are any differences between private and public sites. RESULTS: Of 727 patients screened at 14 sites, 408 (56.1%) failed screening. The data on the specific reasons for screen failures was not available at one of the public sites (38 screen failures out of 83 screened patients). Hence, after excluding that site, further analysis is based on 644 patients, of which 370 failed screening. Of these, 296 (80%) screen failure patients did not meet selection criteria. The majority -266 were HER2 negative. Among logistical issues, 39 patients had inadequate breast tissue sample. Sixteen patients withdrew their consent at private sites as compared to six at public sites. The difference between private and public sites for the above three reasons was statistically significant. CONCLUSION: Use of prescreening logs to reduce the number of patients not meeting selection criteria and protocol logistics, and patient counseling to reduce consent withdrawals could be used to reduce screen failure rate.