Polymicrobial arcanobacterium haemolyticum intracerebral abscess: A case report and review of the literature.

Objective: This article describes a case of polymicrobial Arcanobacterium haemolyticum pharyngitis and sinusitis complicated by intracranial complications and reviews similar cases in the literature. Case summary: A 21-year-old immunocompetent male presented with symptoms of sore throat, rhinorrhoea, lethargy, headache, and rash. Imaging demonstrated sinusitis, pre-septal sinusitis, peritonsillar abscess formation, subdural empyema and cerebritis. He was managed with endoscopic sinus surgery, craniotomy for evacuation of subdural empyema and antibiotics. Microbiological samples demonstrated growth of A. haemolyticum, strep. anginosus, and fusobacterium necrophorum. He subsequently developed a cerebral abscess requiring stereotactic needle drainage. After a prolonged course of antibiotics, the patient was discharge and made a good recovery. Discussion: A. haemolyticum is an uncommon cause of non-streptococcal pharyngitis that may occur alongside other microorganisms and is rarely associated with severe intracranial complications. This organism and its antibiotic susceptibility patterns should be considered in complicated upper respiratory tract infections in immunocompetent hosts. Penicillins and macrolide antibiotics form the mainstay of therapy for A. haemolyticum.

BRAIxDet: Learning to detect malignant breast lesion with incomplete annotations.

Methods to detect malignant lesions from screening mammograms are usually trained with fully annotated datasets, where images are labelled with the localisation and classification of cancerous lesions. However, real-world screening mammogram datasets commonly have a subset that is fully annotated and another subset that is weakly annotated with just the global classification (i.e., without lesion localisation). Given the large size of such datasets, researchers usually face a dilemma with the weakly annotated subset: to not use it or to fully annotate it. The first option will reduce detection accuracy because it does not use the whole dataset, and the second option is too expensive given that the annotation needs to be done by expert radiologists. In this paper, we propose a middle-ground solution for the dilemma, which is to formulate the training as a weakly- and semi-supervised learning problem that we refer to as malignant breast lesion detection with incomplete annotations. To address this problem, our new method comprises two stages, namely: (1) pre-training a multi-view mammogram classifier with weak supervision from the whole dataset, and (2) extending the trained classifier to become a multi-view detector that is trained with semi-supervised student-teacher learning, where the training set contains fully and weakly-annotated mammograms. We provide extensive detection results on two real-world screening mammogram datasets containing incomplete annotations and show that our proposed approach achieves state-of-the-art results in the detection of malignant breast lesions with incomplete annotations.

Biplex quantitative PCR to detect transcriptionally active human papillomavirus 16 from patient saliva.

Head and neck cancers, particularly oropharyngeal cancers (OPC), have been increasingly associated with human papillomavirus (HPV) infections, specifically HPV16. The current methods for HPV16 detection primarily rely on p16 staining or PCR techniques. However, it is important to note the limitations of conventional PCR, as the presence of viral DNA does not always indicate an ongoing viral infection. Moreover, these tests heavily rely on the availability of tissue samples, which can present challenges in certain situations. In this study, we developed a RT-qPCR biplex approach to detect HPV16 oncogenes E6 and E7 RNA in saliva samples from OPC patients. Salivary supernatant was used as the liquid biopsy source. We successfully obtained RNA from salivary supernatant, preserving its integrity as indicated by the detection of several housekeeping genes. Our biplex approach accurately detected E6 and E7 RNA in HPV16-positive cell lines, tissues, and finally in OPC salivary samples. Importantly, the assay specifically targeted HPV16 and not HPV18. This biplexing technique allowed for reduced sample input without compromising specificity. In summary, our approach demonstrates the potential to detect viable HPV16 in saliva from OPC patients. Since the assay measures HPV16 RNA, it provides insights into the transcriptional activity of the virus. This could guide clinical decision-making and treatment planning for individuals with HPV-related OPC.

First Phase Development of a Patient-reported Outcome Measure for Midface Oncology.

Background: Facial cancer surgery involving the midface (comprising the lower eyelids, nose, cheeks, and upper lip) can have debilitating life-changing functional, social, and psychological impacts on the patient. Midface symptoms are inadequately captured by existing patient-reported outcome measures (PROMs). PROMs are increasingly used for individual patient care, quality improvement, and standardized reporting of treatment outcomes. This study aimed to present our findings from the first phase of the development of a midface, specifically periocular and nasal, PROM. Methods: After international guidance for PROM development, the first phase comprised identification of salient issues and item generation. Fifteen patients who had midface surgery and 10 clinicians from various specialties with more than 5 years' experience treating these patients were recruited. Semi-structured interviews explored aesthetic, functional, social, and psychological outcomes, with specific attention to deficiencies in current PROMs. Thematic analysis was used to develop an item pool, and group interviews with clinicians were carried out to create and refine PROM scales. Results: Qualitative data from patient interviews were grouped into aesthetic, functional, and psychosocial domains for the eyelids and nose. Ninety-nine draft items were generated across these domains. Following focus group discussions, the final version of the midface-specific PROM contained 31 items (13 eye-specific, 10-nose-specific, eight general midface items). Conclusions: This midface-specific PROM is valuable in assessing and comparing patient-reported outcomes in those who have undergone complex resection and reconstruction of the midface. This PROM is currently undergoing field testing.

Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation.

Background: Boiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity. However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease. Methods: BH was applied using a sparse scan (1 mm spacing between sonications) protocol to B16F10-ZsGreen melanoma in bilateral and unilateral settings. Ipsilateral and contralateral tumor growth was measured. Flow cytometry was used to track ZsGreen antigen and assess how BH drives dendritic cell behavior. Results: BH monotherapy elicited ipsilateral and abscopal tumor control in this highly aggressive model. Tumor antigen presence in immune cells in the tumor-draining lymph nodes (TDLNs) was ~3-fold greater at 24h after BH, but this abated by 96h. B cells, macrophages, monocytes, granulocytes, and both conventional dendritic cell subsets (i.e. cDC1s and cDC2s) acquired markedly more antigen with BH. BH drove activation of both cDC subsets, with activation being dependent upon tumor antigen acquisition. Our data also suggest that BH-liberated tumor antigen is complexed with damage-associated molecular patterns (DAMPs) and that cDCs do not traffic to the TDLN with antigen. Rather, they acquire antigen as it flows through afferent lymph vessels into the TDLN. Conclusion: When applied with a sparse scan protocol, BH monotherapy elicits abscopal melanoma control and shapes dendritic cell function through several previously unappreciated mechanisms. These results offer new insight into how to best combine BH with immunotherapies for the treatment of metastatic melanoma.

Associations between patient-level health literacy and diagnostic time intervals for head and neck cancer: A prospective cohort study.

BACKGROUND: Health literacy (HL) comprises skills and knowledge required to understand, access, and make decisions about healthcare. Our aim was to examine associations between patient HL and time intervals (defined in the Aarhus statement) along the pathway to treatment of head and neck cancer (HNC). METHODS: A prospective cohort study was conducted from October 2018 to March 2020. Participants completed the Health Literacy Questionnaire (HLQ®) and described key events and dates along the pathway to treatment using validated questionnaires. Correlations between six diagnostic time intervals and domains of HL were explored, and factors predicting exceeding maximum acceptable timeframes were assessed using logistic regression. RESULTS: One hundred patients with a diagnosis of HNC within the preceding 6 months were recruited. HLQ® Domain 2 (sufficient information to manage health) was significantly negatively associated with four intervals: the patient interval (first symptom to first presentation), primary care interval (first presentation to referral to secondary care), diagnostic interval (first presentation to diagnosis), and total interval (first symptom to treatment onset); correlation coefficients -0.25 to -0.27 (P < 0.05). Domain 8 (ability to find good information) was significantly negatively associated with three intervals (primary care interval, diagnostic interval, and total interval; correlation coefficients -0.23 to -0.34; P < 0.05). Higher education, age, and comorbidity levels were associated with shorter patient and diagnostic intervals. CONCLUSIONS: HL may be a potential target to improve timeliness of HNC diagnosis and reduce disparities in outcomes.

Distress about social problems and tobacco and cannabis use outcomes among young adults in Los Angeles County.

OBJECTIVE: To examine associations of concern, worry, and stress about discrimination, shootings/violence, and police brutality and exclusive and dual tobacco and cannabis use among young adults. METHODS: A prospective, racially/ethnically diverse cohort of young adults (n = 1960) living in Los Angeles, California completed a baseline survey in 2020 (age range: 19-23) and a follow-up survey in 2021. Exploratory factor analysis (EFA) was employed on nine variables assessing levels of concern, worry, and stress about societal discrimination, societal shootings/violence, and community police brutality at baseline. Past 30-day tobacco and cannabis use at follow-up was categorized as current exclusive tobacco, exclusive cannabis, and dual tobacco and cannabis (vs never/former) use based on eleven use variables. Multinomial logistic regressions estimated adjusted associations between each factor score (translated to standard deviation units) with exclusive and dual tobacco and cannabis use. RESULTS: The EFA produced four factor scores representing concern/worry/stress (i.e., distress) about community police brutality (F1), distress about societal shootings/violence (F2), and distress about societal discrimination (F3), as well as generalized stress about police brutality, shootings/violence, and discrimination (F4). F1, F2, and F3 were associated with subsequent exclusive current cannabis use, with F1 having the strongest association (OR: 1.35, 95% CI: 1.18-1.55), while only F1 (OR: 1.51, 95% CI: 1.27-1.78) was associated with dual tobacco and cannabis use. None of the factors were associated with exclusive tobacco use. CONCLUSIONS: Young adult concern, worry, and/or stress about social problems may increase risk of cannabis use with or without concurrent tobacco use 6-12 months later.

When should patients with T1N0 oral squamous cell carcinoma be considered for elective neck dissection?

AIMS: To identify adverse pathological features (APF) predicting nodal failure in clinically node negative T1 oral squamous cell carcinoma (OSCC). METHODOLOGY: This study evaluated patients with T1N0 (≤5 mm depth of invasion (DOI) and ≤2 cm diameter) oral cancers from a prospectively maintained database between 1988 and 2020. All patients underwent surgical excision of the primary lesion without neck dissection. Patients underwent three monthly clinical surveillance and salvage neck dissection was performed if nodal relapse was diagnosed. RESULTS: Overall, 141 patients were included. Nodal relapse was reported in 16/141 (11.3%) patients. Factors impacting regional recurrence-free survival were DOI ≥3 mm (HR: 2.4, P < 0.001), maximum tumour diameter ≥12 mm (HR: 1.1, P = 0.009), perineural invasion (PNI) (HR 7.5, P = 0.002) and poor differentiation (HR 5.3, P = 0.01). Rates of nodal relapse increased from 2% amongst patients with no APFs to 100% for those with four APFs. Patients with two or more APFs had significantly poorer 5-year regional recurrence-free survival (94.8% vs. 56.3%, P < 0.001). CONCLUSION: Patients with T1N0 OSCC with two or more APFs (DOI ≥3 mm, diameter ≥12 mm, PNI or poor differentiations) should be considered for elective neck dissection.

An Interpretable and Accurate Deep-Learning Diagnosis Framework Modeled With Fully and Semi-Supervised Reciprocal Learning.

The deployment of automated deep-learning classifiers in clinical practice has the potential to streamline the diagnosis process and improve the diagnosis accuracy, but the acceptance of those classifiers relies on both their accuracy and interpretability. In general, accurate deep-learning classifiers provide little model interpretability, while interpretable models do not have competitive classification accuracy. In this paper, we introduce a new deep-learning diagnosis framework, called InterNRL, that is designed to be highly accurate and interpretable. InterNRL consists of a student-teacher framework, where the student model is an interpretable prototype-based classifier (ProtoPNet) and the teacher is an accurate global image classifier (GlobalNet). The two classifiers are mutually optimised with a novel reciprocal learning paradigm in which the student ProtoPNet learns from optimal pseudo labels produced by the teacher GlobalNet, while GlobalNet learns from ProtoPNet's classification performance and pseudo labels. This reciprocal learning paradigm enables InterNRL to be flexibly optimised under both fully- and semi-supervised learning scenarios, reaching state-of-the-art classification performance in both scenarios for the tasks of breast cancer and retinal disease diagnosis. Moreover, relying on weakly-labelled training images, InterNRL also achieves superior breast cancer localisation and brain tumour segmentation results than other competing methods.

Discrimination and Tobacco Use Outcomes Among US Adults: Effect Modification by Race/Ethnicity.

INTRODUCTION: Racial/ethnic discrimination (hereafter, discrimination) is associated with tobacco use. However, little is known about the relationship between discrimination and dual/polytobacco use and tobacco use disorder (TUD), including how these relationships vary by race/ethnicity. METHODS: Data on adults 18 and older come from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (n = 35,881). Past-year discrimination was measured using the Experiences of Discrimination scale. Past 30-day exclusive, dual, and polytobacco use was measured as the mutually exclusive use of any combination of four types of tobacco products: cigarettes, electronic nicotine delivery systems, other combustibles (i.e., cigars and pipe), and smokeless tobacco. Past-year TUD was defined according to DSM-5 criteria. Associations between discrimination and exclusive, dual, and polytobacco use and discrimination and TUD were estimated using multinomial logistic regression and logistic regression, respectively. Models were stratified by race/ethnicity (i.e., Hispanic, non-Hispanic (NH) White, NH Black, another race/ethnicity) to assess effect modification. RESULTS: Adults who used tobacco and who had TUD was 24.2% and 19.2%, respectively. More discrimination was associated with higher odds of exclusive, dual, and polytobacco use as well as TUD. Models stratified by race/ethnicity suggest that discrimination was associated with dual/polytobacco use among NH Black adults (OR: 1.05, 95% CI: 1.002-1.11) and NH White adults (OR: 1.18, 95% CI: 1.13-1.22). While more discrimination was associated with TUD among all racial/ethnic groups, the relationship was the strongest for NH White adults. CONCLUSIONS: Discrimination was associated with more severe tobacco use outcomes among multiple racial/ethnic groups, but associations were the strongest for NH White adults.

Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation.

Background: Boiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity. However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease. Methods: BH was applied using a sparse scan (1 mm spacing between sonications) protocol to B16F10-ZsGreen melanoma in bilateral and unilateral settings. Ipsilateral and contralateral tumor growth was measured. Flow cytometry was used to track ZsGreen antigen and assess how BH drives dendritic cell behavior. Results: BH monotherapy elicited ipsilateral and abscopal tumor control in this highly aggressive model. Tumor antigen presence in immune cells in the tumor-draining lymph nodes (TDLNs) was ~3-fold greater at 24h after BH, but this abated by 96h. B cells, macrophages, monocytes, granulocytes, and both conventional dendritic cell subsets (i.e. cDC1s and cDC2s) acquired markedly more antigen with BH. BH drove activation of both cDC subsets, with activation being dependent upon tumor antigen acquisition. Our data also suggest that BH-liberated tumor antigen is complexed with damage-associated molecular patterns (DAMPs) and that cDCs do not traffic to the TDLN with antigen. Rather, they acquire antigen as it flows through afferent lymph vessels into the TDLN. Conclusion: When applied with a sparse scan protocol, BH monotherapy elicits abscopal melanoma control and shapes dendritic cell function through several previously unappreciated mechanisms. These results offer new insight into how to best combine BH with immunotherapies for the treatment of metastatic melanoma.

Surrogacy validation for time-to-event outcomes with illness-death frailty models.

A common practice in clinical trials is to evaluate a treatment effect on an intermediate outcome when the true outcome of interest would be difficult or costly to measure. We consider how to validate intermediate outcomes in a causally-valid way when the trial outcomes are time-to-event. Using counterfactual outcomes, those that would be observed if the counterfactual treatment had been given, the causal association paradigm assesses the relationship of the treatment effect on the surrogate outcome with the treatment effect on the true, primary outcome. In particular, we propose illness-death models to accommodate the censored and semicompeting risk structure of survival data. The proposed causal version of these models involves estimable and counterfactual frailty terms. Via these multistate models, we characterize what a valid surrogate would look like using a causal effect predictiveness plot. We evaluate the estimation properties of a Bayesian method using Markov chain Monte Carlo and assess the sensitivity of our model assumptions. Our motivating data source is a localized prostate cancer clinical trial where the two survival outcomes are time to distant metastasis and time to death.

Cigarette Prices and Disparities in Cessation in the United States.

INTRODUCTION: Achieving cessation in people with established smoking patterns remains a challenge. Increasing cigarette prices has been one of the most effective strategies for lowering smoking rates. It remains unclear how effective it has been in encouraging cessation among adults in recent years and how the effectiveness varies by sociodemographic characteristics. METHODS: Using repeated cross-sectional data collected by the Tobacco Use Supplement of the Current Population Survey, we investigate the relationship between cigarette prices and cessation from 2003 to 2019 in adults 25+. We examine the associations between price and cessation in the population overall and by sex, race/ethnicity, and socioeconomic status. RESULTS: We found mixed support for associations between greater local prices and cessation. Unadjusted models showed that greater local prices were associated with greater odds of cessation, but the associations did not persist after controlling for sociodemographic characteristics. The associations did not significantly differ by respondent characteristics. Sensitivity analysis using alternative specifications and retail state price as the main predictor showed similar results. Sensitivity analysis with controls for e-cigarette use in the 2014-2019 period showed that greater local price was associated with cessation among adults with less than a high school degree. When stratified by year of data collection, results show that greater local prices were associated with cessation after 2009. CONCLUSIONS: Overall, the study adds to the conflicting evidence on the effectiveness of increasing prices on smoking cessation among adults with established smoking patterns. IMPLICATIONS: Higher cigarette prices have been one of the most effective tools for lowering smoking prevalence. It remains unclear how effective they are in encouraging adults with established smoking patterns to quit. Results show that greater local prices were associated with higher odds of cessation, but the association did not persist after sociodemographic adjustment. In a sensitivity analysis, greater local price was associated with cessation among people with less than a high school degree in models controlling for e-cigarette use. We also found evidence that greater local price was associated with cessation after 2009. More comprehensive smoke-free coverage was also associated with greater odds of cessation. The study's results highlight that encouraging cessation among adults with an established smoking pattern remains a challenging policy problem even when cigarette prices rise.

Racial and Ethnic Disparities in Mental Health Problems and Tobacco and Cannabis Use Among US Emerging Adults.

INTRODUCTION: Mental health problems in emerging adulthood are linked to tobacco and cannabis use, but whether race and ethnicity modifies these associations is unclear. METHODS: We used data from wave 4 of the Population Assessment of Tobacco and Health Study (youth n = 6898, young adult n = 10,304) to conduct latent class analysis (LCA) of six past 30-day tobacco and cannabis use indicators (i.e., cigarettes, electronic nicotine delivery systems (ENDS), cigars, blunts, cannabis vaping, other cannabis). We estimated associations between past 30-day internalizing and externalizing (i.e., low (referent), moderate, high) problems and latent classes of tobacco/cannabis use (vs. never/former use) using adjusted multinomial logistic regression. We explored whether associations varied by race and ethnicity through stratification. RESULTS: We identified four exclusive use latent classes and two dual/poly use latent classes for both youth and young adult samples. Race/ethnicity-stratified models identified associations between internalizing/externalizing problems and most use classes for Hispanic and non-Hispanic White youth/young adults, with mixed results for non-Hispanic Black youth/young adults. For example, Hispanic (OR: 2.50, 95% CI: 1.09-5.74) and non-Hispanic White (OR: 1.90, 95% CI: 1.18-3.06) youth with high internalizing problems had higher odds of ENDS + cannabis vaping. Externalizing problems were not associated with use among non-Hispanic Black youth while internalizing problems were not associated with use among non-Hispanic Black young adults. CONCLUSION: We observed racial/ethnic variation in mental health problems and tobacco and cannabis use. Understanding mental health problem and tobacco product and cannabis use comorbidity may better inform culturally relevant interventions aimed to prevent and reduce use.

Patient-reported experiences and satisfaction with head and neck surgery outreach clinics in regional New South Wales, Australia: A cross-sectional survey.

RATIONALE: Head and neck surgery services are increasingly being centralised in Australia. Outreach models can overcome burdens of travel that patients in regional and rural areas experience when attending routine appointments, by providing services closer to home. AIM: To explore patient-reported experiences and satisfaction with regional outreach services for head and neck surgery in Australia. METHODS: Patients who attended two regional outreach clinics in New South Wales (NSW), Australia, were surveyed over a 6-month period. Patients completed the Outpatient Cancer Clinics Survey (2020 version) that explored perceptions and experiences of the clinic. Patients with cancer were asked to complete the Edmonton Symptom Assessment System and the Communication and Attitudinal Self-Efficacy scale. Descriptive statistics and analysis of data was performed, and results were compared to the NSW statewide Outpatient Cancer Clinics Survey (2020). Content analysis of free text responses was performed. RESULTS: Some 128 patients responded (56% response rate; mean age 67.2 years, 46.1% female). Compared to the 2020 NSW survey, a higher proportion of patients in our cohort responded positively to 14 of the 26 questions, with the greatest differences observed for questions regarding waiting area comfort (+12.1%, p = 0.008), being informed about different treatment options (+9.5%, p = 0.04), and issues relating to parking (+9.5%, p = 0.03). A lower proportion of our sample responded positively to the question about whether health professionals knew enough about their medical history (-19.3%, p < 0.001). Respondents appreciated having a local clinic that helped them avoid travel to major cities and associated expenses and highlighted benefits of expert consultation and timeliness of investigations. However, cost of appointments and level of reimbursements remain barriers for some patients. CONCLUSIONS: Patients had a high level of satisfaction with regional outreach clinics for head and neck surgery across most domains, indicating patients highly value this service.

Efferocytosis by bone marrow mesenchymal stromal cells disrupts osteoblastic differentiation via mitochondrial remodeling.

The efficient clearance of dead and dying cells, efferocytosis, is critical to maintain tissue homeostasis. In the bone marrow microenvironment (BMME), this role is primarily fulfilled by professional bone marrow macrophages, but recent work has shown that mesenchymal stromal cells (MSCs) act as a non-professional phagocyte within the BMME. However, little is known about the mechanism and impact of efferocytosis on MSCs and on their function. To investigate, we performed flow cytometric analysis of neutrophil uptake by ST2 cells, a murine bone marrow-derived stromal cell line, and in murine primary bone marrow-derived stromal cells. Transcriptional analysis showed that MSCs possess the necessary receptors and internal processing machinery to conduct efferocytosis, with Axl and Tyro3 serving as the main receptors, while MerTK was not expressed. Moreover, the expression of these receptors was modulated by efferocytic behavior, regardless of apoptotic target. MSCs derived from human bone marrow also demonstrated efferocytic behavior, showing that MSC efferocytosis is conserved. In all MSCs, efferocytosis impaired osteoblastic differentiation. Transcriptional analysis and functional assays identified downregulation in MSC mitochondrial function upon efferocytosis. Experimentally, efferocytosis induced mitochondrial fission in MSCs. Pharmacologic inhibition of mitochondrial fission in MSCs not only decreased efferocytic activity but also rescued osteoblastic differentiation, demonstrating that efferocytosis-mediated mitochondrial remodeling plays a critical role in regulating MSC differentiation. This work describes a novel function of MSCs as non-professional phagocytes within the BMME and demonstrates that efferocytosis by MSCs plays a key role in directing mitochondrial remodeling and MSC differentiation. Efferocytosis by MSCs may therefore be a novel mechanism of dysfunction and senescence. Since our data in human MSCs show that MSC efferocytosis is conserved, the consequences of MSC efferocytosis may impact the behavior of these cells in the human skeleton, including bone marrow remodeling and bone loss in the setting of aging, cancer and other diseases.

Persisting facial nerve palsy or trigeminal neuralgia - red flags for perineural spread of head and neck cutaneous squamous cell carcinoma (HNcSCC).

BACKGROUND: Perineural spread (PNS) of head and neck cutaneous squamous cell carcinoma (HNcSCC) is a unique diagnostic challenge, presenting with insidious trigeminal (CN V) or facial nerve (CN VII) neuropathies without clinically discernible primary masses. These patients are often sub-optimally investigated and misdiagnosed as Bell's palsy or trigeminal neuralgia. This case series highlights the red flags in history and pitfalls that lead to delays to diagnosis and treatment. METHODS: A retrospective case series of 19 consecutive patients with complete clinical histories with HNcSCC PNS without an obvious cutaneous primary lesion at time of presentation to a quaternary head and neck centre in Australia were identified and included for analysis. RESULTS: Fifteen had CN VII PNS, 17 had CN V PNS, and 13 had both. The overall median symptom-to-diagnosis time was 12-months (IQR-15 months). Eight patients had CN VII PNS and described progressive segmental facial nerve palsy with a median symptom-to-diagnosis time of 9-months (IQR-11.75 months). Eleven patients had primary CN V PNS and described well localized parathesia, formication or neuralgia with a median symptom-to-diagnosis time of 19-months (IQR 27.5 months). CONCLUSION: PNS is often mistaken for benign cranial nerve dysfunction with delays in diagnosis worsening prognosis. Red flags such as progressive CN VII palsy or persistent CN V paraesthesia, numbness, formication or pain, particularly in the presence of immuno-compromise and/or a history of facial actinopathy should raise suspicion for PNS. Gadolinium-enhanced MR Neurography should be obtained expediently in patients with persistent/progressive CN V/CN VII palsies in patients with red flags, with low threshold for referral to a Head and Neck Surgeon.

Latent Classes of Tobacco and Cannabis Use among Youth and Young Adults in the United States.

Background: Research characterizing patterns of tobacco and cannabis use by product type and route of administration among youth and young adults (YAs) is limited. Methods: We conducted latent class analysis of tobacco and cannabis use (i.e., cigarettes, electronic nicotine delivery systems (ENDS), cigars, blunts, cannabis vaping, and other cannabis use (without blunting/vaping)) among youth (ages 15-17) and YAs (ages 18-24) who used at least one product in the past 30 days, using data from the Population Assessment of Tobacco and Health Study (Wave 4, 2016-2017). We used multinomial logistic regression models to examine associations between sociodemographic characteristics and use classes. Results: The latent use classes for youth included cigarettes (2.5%), ENDS (2.6%), blunts (2.5%), other cannabis (6.3%), ENDS + cannabis vaping (2.7%), and cigarettes + cigars + other cannabis (1.5%), while the latent use classes for YAs included cigarettes (11.7%), ENDS (3.9%), blunts (5.3%), other cannabis (7.0%), cigarettes + cigars (8.2%), and cigarettes + ENDS + cannabis vaping (4.9%). We compared use classes to never/former use for youth (82.0%) and YAs (59.0%) and found that they differed by each sociodemographic characteristic. For example, non-Hispanic Black YAs had higher odds of cigarettes + cigar use compared to non-Hispanic White YAs, whereas racial/ethnic minority youth and YAs had lower odds of other dual/poly use groups compared to their non-Hispanic White counterparts. Conclusions: We observed differences in use classes by sociodemographic characteristics for youth and YAs. Health professionals must consider tobacco and cannabis use patterns when implementing prevention and cessation interventions.