Landscape of HER2-low breast cancer: Insights from a six-year study on prevalence and clinicopathological characteristics.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+/2+ in immunohistochemistry (IHC) and absence of ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2-low breast cancer to novel anti-HER2 antibody-drug-conjugates. Data on characteristics of HER2-low breast cancer subtype is limited. Real-world data from the Anatomic Pathology Department of Hotel-Dieu de France, spanning 2017-2023, was retrospectively collected. HER2-positive patients were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Clinicopathological characteristics between the groups were compared using a Chi-Squared test. Out of 1195 patients, we observed 341 (28.5 %) HER2-low breast cancers cases. HER2-positive breast cancer cases (n = 178; 14.9 %) were excluded. There was no significant difference in age and sex between HER2-low and HER2-zero group (p = 0.33 and 0.79, respectively). HER2-low breast cancer was associated with positive estrogen receptor status and positive progesterone receptor status (p < 0.001 and p = 0.01, respectively). Ductal adenocarcinomas were more commonly observed in HER2-low group (p < 0.001). When stratified by hormone (HR) status, 87.4 % of patients had HR-positive status and 12.6 % were HR-negative. Among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (25%vs.10 %, p = 0.04). This study showed that HER2-low is distinct from HER2-zero and is common among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Within HR-negative breast cancer, those with low HER2 expression exhibit a less aggressive profile compared to HER2-zero tumors.

Association between Early Basal Ganglia and Thalami Perfusion Assessed by Color Doppler Ultrasonography and Brain Injury in Infants with Hypoxic-Ischemic Encephalopathy: A Prospective Cohort Study.

OBJECTIVE: To evaluate associations between neurologic outcomes and early measurements of basal ganglia (BG) and thalamic (Th) perfusion using color Doppler ultrasonography (CDUS) in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Prospective study of infants with mild (n = 18), moderate (n = 17), and severe HIE (n = 14) and controls (n = 17). Infants with moderate-severe HIE received therapeutic hypothermia (TH). CDUS was performed at 24-36 hours and brain magnetic resonance imaging (MRI) at a median of 10 days. Development was followed through 2.5-5 years. The primary outcome was the association between BG and Th perfusion and brain MRI injury. Secondary analyses focused on associations between perfusion measurements and admission neurologic examinations, MRI scores in infants treated with TH, and motor and sensory disability, or death. An exploratory analysis assessed the accuracy of BG and Th perfusion to predict brain MRI injury in infants treated with TH. RESULTS: Increased BG and Th perfusion on CDUS was observed in infants with severe MRI scores and those with significant motor and neurosensory disability or death through 2.5-5 years (P < .05). Infants with severe HIE showed increased BG and Th perfusion (P < .005) compared with infants with moderate HIE. No differences were identified between the between the control and mild HIE groups. Th perfusion ≥0.237 cm/second (Area under the curve of 0.824) correctly classified 80% of infants with severe MRI scores. CONCLUSIONS: Early dynamic CDUS of the BG and Th is a potential biomarker of severe brain injury in infants with HIE and may be a useful adjunct to currently used assessments.

Investigating the role of CFTR in human and mouse myometrium.

Background: Abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) has been linked to airway smooth muscle abnormalities including bronchial hyperresponsiveness. However, a role for CFTR in other types of smooth muscle, including myometrium, remains largely unexplored. As CF life expectancy and the number of pregnancies increases, there is a need for an understanding of the potential role of CFTR in myometrial function. Methods: We investigated the role of CFTR in human and mouse myometrium. We used immunofluorescence to identify CFTR expression, and carried out contractility studies on spontaneously contracting term pregnant and non-pregnant mouse myometrium and term pregnant human myometrial biopsies from caesarean sections. Results: CFTR was found to be expressed in term pregnant mouse myometrium. Inhibition of CFTR, with the selective inhibitor CFTRinh-172, significantly reduced contractility in pregnant mouse and human myometrium in a concentration-dependent manner (44.89 ± 11.02 term pregnant mouse, 9.23 ± 4.75 term-pregnant human; maximal effect at 60 µM expressed as a percentage of the pre-treatment control period). However, there was no effect of CFTRinh-172 in non-pregnant myometrium. Conclusion: These results demonstrate decreased myometrial function when CFTR is inhibited, which may have implications on pregnancy and labour outcome and therapeutic decisions for labour in CF patients.

Acute encephalopathy with biphasic seizures and late reduced diffusion with concurrent transverse myelitis.

We describe a patient with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) with unique features, including concurrent transverse myelitis. A 2-year-old previously healthy girl had clinical findings consistent with AESD, occurring in association with influenza A infection. The posterior brain regions were most severely affected, resulting in cortical blindness. She also developed bilateral limb weakness, and spine MRI revealed transverse myelitis in the cervical region. She was treated acutely with intravenous methylprednisolone. Serum anti-myelin oligodendrocyte glycoprotein and anti-aquaporin-4 antibodies were negative, as was an anti-extractable nuclear antigen panel. Although her clinical presentation was severe, she improved dramatically over the following months, and 6 months following initial presentation, her parents felt she had returned to baseline. This is the first report of AESD occurring in combination with transverse myelitis. The co-occurrence of the two conditions is unlikely to be coincidental, suggesting that there may be a shared or overlapping immunological pathway involved. The patient's recovery was impressive, which could partially relate to the acute treatment with corticosteroids.

Does a novel community-based outpatient palliative care intervention for Parkinson's disease and related disorders improve care? Qualitative results from patients and care partners.

BACKGROUND: Palliative care has the potential to address significant unmet needs in people with Parkinson's disease and related disorders, but models that rely on in-person specialty palliative care teams have limited scalability. AIM: To describe patient and care partner experiences with a novel, community-based palliative care intervention for Parkinson's disease. DESIGN: Qualitative study embedded in a randomized clinical trial to document participant experiences with a novel palliative care intervention (community neurologist training and remote team-based specialist palliative care). Transcripts were coded and thematically analyzed through a combination of team-based inductive and deductive coding. SETTING/PARTICIPANTS: Twenty-eight patients and 33 care partners purposively sampled from participants in a randomized clinical trial of a palliative care intervention for Parkinson's disease and related disorders conducted at nine sites. RESULTS: Benefits of the intervention included management of a wider range of non-motor symptoms, facilitation of conversations about the future, greater engagement with the health care team, and increased referrals to resources. Participants identified areas of improvement, including uptake of palliative care training by community neurologists, additional prognostic counseling, and clarity and timeliness of communication with the multidisciplinary team. CONCLUSIONS: Clinicians caring for people with Parkinson's disease and related disorders should screen for non-motor symptoms, provide regular prognostic counseling, and refer to specialty palliative care services earlier in the course of illness. Future interventions should be designed to promote uptake of palliative care training by community neurologists and further optimize referral to and coordination with in-person or remote specialty palliative teams.

Classic "PCH" Genes are a Rare Cause of Radiologic Pontocerebellar Hypoplasia.

The term Pontocerebellar Hypoplasia (PCH) was initially used to designate a heterogeneous group of fetal-onset genetic neurodegenerative disorders. As a descriptive term, PCH refers to pons and cerebellum of reduced volume. In addition to the classic PCH types described in OMIM, many other disorders can result in a similar imaging appearance. This study aims to review imaging, clinical and genetic features and underlying etiologies of a cohort of children with PCH on imaging. We systematically reviewed brain images and clinical charts of 38 patients with radiologic evidence of PCH. Our cohort included 21 males and 17 females, with ages ranging between 8 days to 15 years. All individuals had pons and cerebellar vermis hypoplasia, and 63% had cerebellar hemisphere hypoplasia. Supratentorial anomalies were found in 71%. An underlying etiology was identified in 68% and included chromosomal (21%), monogenic (34%) and acquired (13%) causes. Only one patient had pathogenic variants in an OMIM listed PCH gene. Outcomes were poor regardless of etiology, though no one had regression. Approximately one third of patients deceased at a median age of 8 months. All individuals had global developmental delay, 50% were non-verbal, 64% were non-ambulatory and 45% required gastrostomy feeding. This cohort demonstrates that radiologic PCH has heterogenous etiologies and the "classic" OMIM-listed PCH genes underlie only a minority of cases. Broad genetic testing, including chromosomal microarray and exome or multigene panels, is recommended in individuals with PCH-like imaging appearance. Our results strongly suggest that the term PCH should be used to designate radiologic findings, and not to imply neurogenerative disorders.

Patient and Family Outcomes of Community Neurologist Palliative Education and Telehealth Support in Parkinson Disease.

Importance: Parkinson disease and related disorders (PDRD) are the fastest growing neurodegenerative illness in terms of prevalence and mortality. As evidence builds to support palliative care (PC) for PDRD, studies are needed to guide implementation. Objective: To determine whether PC training for neurologists and remote access to a PC team improves outcomes in patients with PDRD in community settings. Design, Setting, and Participants: This pragmatic, stepped-wedge comparative effectiveness trial enrolled and observed participants from 19 community neurology practices supported by PC teams at 2 academic centers from March 8, 2017, to December 31, 2020. Participants were eligible if they had PDRD and moderate to high PC needs. A total of 612 persons with PDRD were referred; 253 were excluded. Patients were excluded if they had another diagnosis meriting PC, were receiving PC, or were unable or unwilling to follow study procedures. Patients received usual care or the intervention based on when their community neurologist was randomized to start the intervention. Data were analyzed from January 2021 to September 2023. Intervention: The intervention included (1) PC education for community neurologists and (2) team-based PC support via telehealth. Main Outcomes and Measures: The primary outcomes were differences at 6 months in patient quality of life (QOL; measured by the Quality of Life in Alzheimer Disease Scale [QOL-AD]) and caregiver burden (Zarit Burden Interview) between the intervention and usual care. Results: A total of 359 patients with PDRD (233 men [64.9%]; mean [SD] age, 74.0 [8.8] years) and 300 caregivers were enrolled. At 6 months, compared with usual care, participants receiving the intervention had better QOL (QOL-AD score, 0.09 [95% CI, -0.63 to 0.82] vs -0.88 [95% CI, -1.62 to -0.13]; treatment effect estimate, 0.97; 95% CI, 0.07-1.86; P = .03). No significant difference was observed in caregiver burden (Zarit Burden Interview score, 1.19 [95% CI, 0.16 to 2.23] vs 0.55 [95%, -0.44 to 1.54]; treatment effect estimate, 0.64; 95% CI, -0.62 to 1.90; P = .32). Advance directive completion was higher under the intervention (19 of 38 [50%] vs 6 of 31 [19%] among those without directives at the beginning of the study; P = .008). There were no differences in other outcomes. Conclusions and Relevance: PC education for community neurologists and provision of team-based PC via telehealth is feasible and may improve QOL and advance care planning. Overall treatment effects were small and suggest opportunities to improve both the intervention and implementation. Trial Registration: ClinicalTrials.gov Identifier: NCT03076671.

The "Surprise Question" for Prognostication in People With Parkinson's Disease and Related Disorders.

CONTEXT: Parkinson's disease and related disorders (PDRD) are fatal neurodegenerative disorders characterized by a fluctuating course that can complicate prognostication. The "surprise question" (SQ: "Would you be surprised if your patient died in the next year?") has been used to identify patients with limited prognosis but has not been assessed in PDRD. OBJECTIVES: To determine the validity of the SQ in predicting 12-month mortality in PDRD. METHODS: Data was analyzed from 301 patients and 34 community-based neurologists who were participating in a clinical trial of outpatient palliative care for patients with PDRD. Clinicians answered the SQ for each patient at baseline. Descriptive statistics at baseline, chi-square tests of independence, 2 × 2 and 2 × 3 cross tables were used. Survival analysis compared SQ responses using Kaplan-Meier curves. Risk estimate analyses identified patient characteristics associated with clinicians' responses. RESULTS: Mortality was 10.3% (N = 31) at 1 year. The sensitivity and specificity of the SQ was 80.7% and 58.9%, respectively with AUC = 0.70, positive predictive value of 18.4% and negative predictive value of 96.4%. Older age, atypical parkinsonism, and dementia were associated with responding "no" to the SQ. CONCLUSION: The SQ is sensitive to 12-month mortality in PDRD, with a high negative predictive value. The SQ may be useful for identifying patients less likely to die within a year and may be useful for identifying patients with palliative care needs outside of end-of-life care. This latter use may assist in mobilizing early and timely referral to specialist palliative care.

Feasibility and Safety of Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-01): A Randomized, Double-blind, Placebo-controlled Phase Ib Clinical Trial.

OBJECTIVE: To test feasibility and safety of administering sildenafil in neonates with neonatal encephalopathy (NE), developing brain injury despite therapeutic hypothermia (TH). STUDY DESIGN: We performed a randomized, double-blind, placebo-controlled phase Ib clinical trial between 2016 and 2019 in neonates with moderate or severe NE, displaying brain injury on day-2 magnetic resonance imaging (MRI) despite TH. Neonates were randomized (2:1) to 7-day sildenafil or placebo (2 mg/kg/dose enterally every 12 hours, 14 doses). Outcomes included feasibility and safety (primary outcomes), pharmacokinetics (secondary), and day-30 neuroimaging and 18-month neurodevelopment assessments (exploratory). RESULTS: Of the 24 enrolled neonates, 8 were randomized to sildenafil and 3 to placebo. A mild decrease in blood pressure was reported in 2 of the 8 neonates after initial dose, but not with subsequent doses. Sildenafil plasma steady-state concentration was rapidly reached, but decreased after TH discontinuation. Twelve percent of neonates (1/8) neonates died in the sildenafil group and 0% (0/3) in the placebo group. Among surviving neonates, partial recovery of injury, fewer cystic lesions, and less brain volume loss on day-30 magnetic resonance imaging were noted in 71% (5/7) of the sildenafil group and in 0% (0/3) of the placebo group. The rate of death or survival to 18 months with severe neurodevelopmental impairment was 57% (4/7) in the sildenafil group and 100% (3/3) in the placebo group. CONCLUSIONS: Sildenafil was safe and well-absorbed in neonates with NE treated with TH. Optimal dosing needs to be established. Evaluation of a larger number of neonates through subsequent phases II and III trials is required to establish efficacy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT02812433.

Caregiver Influences on Eating Behaviors in Children: An Opportunity for Preventing Obesity.

PURPOSE OF REVIEW: This review seeks to define caregiver practices that impact childhood eating behaviors and identify ways to utilize these relationships to prevent childhood obesity. RECENT FINDINGS: Childhood obesity, which correlates with adult obesity and increased cardiovascular risk, is increasing in prevalence and severity. Caregivers play a significant role in shaping a child's eating behaviors and their predisposition to obesity. Maternal influences during pregnancy and infancy impact a child's future food preferences. Caregiver feeding styles (authoritarian, authoritative, indulgent, and uninvolved) are associated with distinct effects on children's eating behaviors and self-regulation. Authoritative feeding styles promote child autonomy while setting boundaries in the feeding environment. Early caregiver education and coaching regarding nutrition and feeding practices is beneficial to establishing healthy eating behaviors for children. Various caregivers, including parents, grandparents, siblings, teachers, and others, influence a child's eating habits at different stages of development. These caregivers can both positively and negatively impact a child's diet. Comprehensive interventions involving these various caregivers to promote healthy eating practices in children is ideal. Such interventions should be sensitive to cultural and environmental factors. Childhood obesity is a complex issue with long-term health effects. Early intervention using comprehensive approaches including all caregivers, community support, and public policies to address the social determinants of health will be beneficial. Future research should focus on valid outcome measures and equitable interventions that encompass all aspects of a child's life.

Magnetization reversal study of Ni4-xZnxNb2O9compounds using Monte Carlo simulations.

The magnetization reversal (MR) of the layered Ni4-xZnxNb2O9ferrimagnetic compounds, withx=0,0.25,0.50and 0.75, is studied in this work using Monte Carlo (MC) simulations and mean field (MF) calculations. First, we analyze the parent compound to set the parameters of our simulations; testing together MC simulations, MF calculations, and MR experiments reported by Bollettaet al(2022J. Appl. Phys.132153901). Then using two different approaches we fit the MR curves of the series of compounds finding a quite good agreement between MC simulations and the experiments. According to these results, Zn substitutions change the relative contribution to the magnetization of the different layers. Here we present two possible hypotheses to explain this effect; one involving a heterogeneous distribution of Zn2+among the layers, and the other related to distortions of the NiO6octahedra.

Sex-Specific Cerebral Blood Flow Alterations in Youth Operated for Congenital Heart Disease.

Background Lower cerebral blood flow (CBF) has previously been documented preoperatively in neonates with congenital heart disease (CHD). However, it remains unclear if these CBF deficits persist over the life span of CHD survivors following heart surgery. When exploring this question, it is critical to consider the sex differences in CBF that emerge during adolescence. Therefore, this study aimed to compare global and regional CBF between postpubertal youth with CHD and healthy peers and examine if such alterations are related to sex. Methods and Results Youth aged 16 to 24 years who underwent open heart surgery for complex CHD during infancy and age- and sex-matched controls completed brain magnetic resonance imaging, including T1-weighted and pseudo-continuous arterial spin labeling acquisitions. Global gray matter CBF and regional CBF in 9 bilateral gray matter regions were quantified for each participant. Compared with female controls (N=27), female participants with CHD (N=25) presented with lower global and regional CBF. In contrast, there were no differences in CBF between male controls (N=18) and males with CHD (N=17). Concurrently, female controls had higher global and regional CBF compared with male controls, with no differences in CBF between female and male participants with CHD. CBF was lower in individuals with a Fontan circulation. Conclusions This study provides evidence of altered CBF in postpubertal female participants with CHD despite undergoing surgical intervention during infancy. Alterations to CBF could have implications for later cognitive decline, neurodegeneration, and cerebrovascular disease in women with CHD.

Investigating genotype-to-phenotype correlation in CHARGE syndrome by deep phenotyping and multiparametric clustering.

CHARGE syndrome, due to CHD7 pathogenic variations, is an autosomal dominant disorder characterized by a large spectrum of severity. Despite the great number of variations reported, no clear genotype-to-phenotype correlation has been reported. Unsupervised machine learning and clustering was undertaken using a retrospective cohort of 42 patients, after deep radiologic and clinical phenotyping, to establish genotype-phenotype correlation for CHD7-related CHARGE syndrome. It resulted in three clusters showing phenotypes of different severities. While no clear genotype-phenotype correlation appeared within the first two clusters, a single patient was outlying the cohort data (cluster 3) with the most atypical phenotype and the most distal frameshift variant in the gene. We added two other patients with similar distal pathogenic variants and observed a tendency toward mild and/or atypical phenotypes. We hypothesized that this finding could potentially be related to escaping nonsense mediated RNA decay, but found no evidence of such decay in vivo for any of the CHD7 pathogenic variation tested. This indicates that this milder phenotype may rather result from the production of a protein retaining all functional domains.

Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management.

Holoprosencephaly (HPE) is the most common malformation of the prosencephalon in humans. It is characterized by a continuum of structural brain anomalies resulting from the failure of midline cleavage of the prosencephalon. The three classic subtypes of HPE are alobar, semilobar and lobar, although a few additional categories have been added to this original classification. The severity of the clinical phenotype is broad and usually mirrors the radiologic and associated facial features. The etiology of HPE includes both environmental and genetic factors. Disruption of sonic hedgehog (SHH) signaling is the main pathophysiologic mechanism underlying HPE. Aneuploidies, chromosomal copy number variants and monogenic disorders are identified in a large proportion of HPE patients. Despite the high postnatal mortality and the invariable presence of developmental delay, recent advances in diagnostic methods and improvements in patient management over the years have helped to increase survival rates. In this review, we provide an overview of the current knowledge related to HPE, and discuss the classification, clinical features, genetic and environmental etiologies and management.

A comparison of altered white matter microstructure in youth born with congenital heart disease or born preterm.

Introduction: Alterations to white matter microstructure as detected by diffusion tensor imaging have been documented in both individuals born with congenital heart disease (CHD) and individuals born preterm. However, it remains unclear if these disturbances are the consequence of similar underlying microstructural disruptions. This study used multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and neurite orientation dispersion and density imaging (NODDI) to characterize and compare alterations to three specific microstructural elements of white matter - myelination, axon density, and axon orientation - in youth born with CHD or born preterm. Methods: Participants aged 16 to 26 years with operated CHD or born ≤33 weeks gestational age and a group of healthy peers of the same age underwent a brain MRI including mcDESPOT and high angular resolution diffusion imaging acquisitions. Using tractometry, average values of myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index (ODI) were first calculated and compared between groups for 30 white matter bundles. Afterwards, bundle profiling was performed to further characterize the topology of the detected microstructural alterations. Results: The CHD and preterm groups both presented with widespread bundles and bundle segments with lower MWF, accompanied by some occurrences of lower NDI, relative to controls. While there were no differences in ODI between the CHD and control groups, the preterm group presented with both higher and lower ODI compared to the control group and lower ODI compared to the CHD group. Discussion: While youth born with CHD or born preterm both presented with apparent deficits in white matter myelination and axon density, youth born preterm presented with a unique profile of altered axonal organization. Future longitudinal studies should aim to better understand the emergence of these common and distinct microstructural alterations, which could orient the development of novel therapeutic approaches.

Association of novel mutation in TRPV4 with familial nonsyndromic craniosynostosis with complete penetrance and variable expressivity.

OBJECTIVE: The aim of this study was to characterize a novel pathogenic variant in the transient receptor potential vanilloid 4 (TRPV4) gene, causing familial nonsyndromic craniosynostosis (CS) with complete penetrance and variable expressivity. METHODS: Whole-exome sequencing was performed on germline DNA of a family with nonsyndromic CS to a mean depth coverage of 300× per sample, with greater than 98% of the targeted region covered at least 25×. In this study, the authors detected a novel variant, c.496C>A in TRPV4, exclusively in the four affected family members. The variant was modeled using the structure of the TRPV4 protein from Xenopus tropicalis. In vitro assays in HEK293 cells overexpressing wild-type TRPV4 or TRPV4 p.Leu166Met were used to assess the effect of the mutation on channel activity and downstream MAPK signaling. RESULTS: The authors identified a novel, highly penetrant heterozygous variant in TRPV4 (NM_021625.4:c.496C>A) causing nonsyndromic CS in a mother and all three of her children. This variant results in an amino acid change (p.Leu166Met) in the intracellular ankyrin repeat domain distant from the Ca2+-dependent membrane channel domain. In contrast to other TRPV4 mutations in channelopathies, this variant does not interfere with channel activity as identified by in silico modeling and in vitro overexpression assays in HEK293 cells. CONCLUSIONS: Based on these findings, the authors hypothesized that this novel variant causes CS by modulating the binding of allosteric regulatory factors to TRPV4 rather than directly modifying its channel activity. Overall, this study expands the genetic and functional spectrum of TRPV4 channelopathies and is particularly relevant for the genetic counseling of CS patients.

Principles and Validations of an Artificial Intelligence-Based Recommender System Suggesting Acceptable Food Changes.

BACKGROUND: Along with the popularity of smartphones, artificial intelligence-based personalized suggestions can be seen as promising ways to change eating habits toward more desirable diets. OBJECTIVES: Two issues raised by such technologies were addressed in this study. The first hypothesis tested is a recommender system based on automatically learning simple association rules between dishes of the same meal that would make it possible to identify plausible substitutions for the consumer. The second hypothesis tested is that for an identical set of dietary-swaps suggestions, the more the user is-or thinks to be-involved in the process of identifying the suggestion, the higher is their probability of accepting the suggestion. METHODS: Three studies are presented in this article, first, we present the principles of an algorithm to mine plausible substitutions from a large food consumption database. Second, we evaluate the plausibility of these automatically mined suggestions through the results of online tests conducted for a group of 255 adult participants. Afterward, we investigated the persuasiveness of 3 suggestion methods of such recommendations in a population of 27 healthy adult volunteers through a custom designed smartphone application. RESULTS: The results firstly indicated that a method based on automatic learning of substitution rules between foods performed relatively well identifying plausible swaps suggestions. Regarding the form that should be used to suggest, we found that when users are involved in selecting the most appropriate recommendation for them, the resulting suggestions were more accepted (OR = 3.168; P < 0.0004). CONCLUSIONS: This work indicates that food recommendation algorithms can gain efficiency by taking into account the consumption context and user engagement in the recommendation process. Further research is warranted to identify nutritionally relevant suggestions.

Subtle magnetic resonance imaging differences in tegmental pilocytic astrocytomas as a caution against attempting gross-total resection: illustrative cases.

BACKGROUND: Although surgery within the tegmentum of the midbrain is challenging, resection of tegmental pilocytic astrocytomas (PAs) is a standard treatment because this has been shown to outperform chemotherapy and radiotherapy in terms of long-term tumor control. Gross total resection (GTR) assisted by intraoperative neuroelectrophysiological monitoring can be achieved with a reasonable risk-to-benefit ratio, especially for well-circumscribed tumors, but careful scrutiny of magnetic resonance imaging (MRI) is critical to surgical decision making. The authors present two cases of tegmental PAs, which appeared grossly similar on MRI and were operated on via the same surgical approach using the same intraoperative adjuncts. OBSERVATIONS: The tumors had identical histopathological and molecular diagnoses but drastically different functional outcomes for the patients, with significant long-term complications for one of the children, which the authors believe was due to a slightly more invasive nature of this tumor. The authors demonstrate subtle preoperative MRI findings that might be potential clues to a more infiltrative nature of one PA versus another and present pathological findings supporting this argument. LESSONS: This report serves as a reminder that not all tegmental PAs can be managed by the same surgical approach. Subtle signs of infiltration may indicate that GTR should not be attempted.

Large vessel occlusion prediction scales provide high negative but low positive predictive values in prehospital suspected stroke patients.

Introduction: We studied a registry of Emergency Medical Systems (EMS) identified prehospital suspected stroke patients brought to an academic endovascular capable hospital over 1 year to assess the prevalence of disease and externally validate large vessel occlusion (LVO) stroke prediction scales with a focus on predictive values. Methods: All patients had last known well times within 6 hours and a positive prehospital Cincinnati Prehospital Stroke Scale. LVO prediction scale scores were retrospectively calculated from emergency department arrival National Institutes of Health Stroke Scale scores. Final diagnoses were determined by chart review. Prevalence and diagnostic performance statistics were calculated. We prespecified analyses to identify scale thresholds with positive predictive values (PPVs) ≥80% and negative predictive values (NPVs) ≥95%. A secondary analysis identified thresholds with PPVs ≥50%. Results: Of 220 EMS transported patients, 13.6% had LVO stroke, 15.9% had intracranial haemorrhage, 20.5% had non-LVO stroke and 50% had stroke mimic diagnoses. LVO stroke prevalence was 15.8% among the 184 diagnostic performance study eligible patients. Only Field Assessment Stroke Triage for Emergency Destination (FAST-ED) ≥7 had a PPV ≥80%, but this threshold missed 83% of LVO strokes. FAST-ED ≥6, Prehospital Acute Severity Scale =3 and Rapid Arterial oCclusion Evaluation ≥7 had PPVs ≥50% but sensitivities were <50%. Several standard and lower alternative scale thresholds achieved NPVs ≥95%, but false positives were common. Conclusions: Diagnostic performance tradeoffs of LVO prediction scales limited their ability to achieve high PPVs without missing most LVO strokes. Multiple scales provided high NPV thresholds, but these were associated with many false positives.