The Surprising Effect of Priming on SNOT-22 Results.

BACKGROUND: Priming is a psychological phenomenon where subconscious cues in the environment impact our behavioral responses in certain situations. Well studied in the worlds of business, marketing, and even politics, it is unclear how the priming phenomenon impacts patient perception of their own disease state nor how they report that perception using tools like the Sinonasal Outcomes Test (SNOT-22), used to measure that perception in chronic rhinosinusitis. OBJECTIVE: To determine the impact of positive or negative priming on self-reported patient perception of their chronic rhinosinusitis disease using the SNOT-22 disease-specific quality of life instrument. METHODS: Single-blind, randomized, prospective cohort pilot study of 206 consecutive adult patients with a clinical diagnosis of chronic rhinosinusitis presenting to a university rhinology clinic. Patients were randomized to receive "positive priming" (103) or "negative priming" (103) by reading a passage about the positive or negative aspects of chronic sinusitis and its treatment respectively. Patients were then asked to fill out the SNOT-22 and results between the two groups were compared. RESULTS: The negative priming group had a higher median SNOT-22 score of 49 [IQR = 39] compared to the positive priming groups' score of 22 [IQR = 27], p < 0.0001), a difference of nearly three times the minimal clinical impactful difference (MCID). This effect was consistent regardless of age or sex of the patient. Subgroup analysis revealed a greater impact when priming was performed by the senior male attending regardless of patient age or sex (p < 0.001), while priming performed by the younger female research fellow had greater impact on older patients (>59 years, p = 0.001) and female patients (p = 0.003). CONCLUSIONS: Priming impacts how patient's perceive their chronic rhinosinusitis as determined by the SNOT-22. It is imperative that the rhinologist understand this when using this instrument in research applications and in clinical decision-making for patients.

"Left on their own": Left-handedness among rhinologists and otolaryngology trainees.

KEY POINTS: Left-hand-dominant (LHD) respondents reported higher rates of training difficulties because of handedness differences. LHD respondents cited particular difficulty with functional endoscopic sinus surgery. Both LHD and right-hand-dominant respondents perceived a need for laterality-specific training during residency.

Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis.

KEY POINTS: We present the largest cohort of structured histopathology reports on primary ciliary dyskinesia-related chronic rhinosinusitis (PCD-CRS). Despite endoscopic differences, PCD-CRS and cystic fibrosis-related chronic rhinosinusitis (CF-CRS) had similar structured histopathology reports. Compared to healthy patients and those with idiopathic chronic rhinosinusitis without nasal polyps, patients with PCD-CRS had an increased neutrophil count.

Time to treatment patterns of head and neck cancer patients before and during the Covid-19 pandemic.

OBJECTIVES: The delivery of healthcare has changed significantly over the past decades. This study analyzes the clinicodemographic factors and treatment patterns of head and neck squamous cell carcinoma (HNSCC) patients between 2004 and 2020. MATERIALS AND METHODS: Retrospective cohort analysis of HNSCC patients from the National Cancer Data Base from 2004 to 2020. RESULTS: A total of 164,290 patients were included. Increased times from diagnosis to definitive surgery (TTS) were seen across all facility types (academic centers, AC; non-academic centers, NAC) between 2004 and 2019, with NAC affected more. TTS < 15 days (RR = 1.05, 95%CI:1.05-1.09) and > 75 days (1.07, 95%CI:1.05-1.09) were associated with increased mortality risk. This association was more prominent among HPV + HNSCC (RR = 1.45; 95%CI:1.18-1.78). Treatment in AC was associated with a decreased mortality risk (RR = 0.94, 95%CI:0.93-0.95). Despite the universal increase in wait times from 2004 to 2019, short-term mortality was significantly decreased from 2016 to 2019, relative to 2004-2007 (3-month mortality: RR = 0.77, 95%CI:0.70-0.85; 12-month mortality: RR = 0.80, 95%CI:0.77-0.84). Wait times decreased in 2020. CONCLUSIONS: TTS increased between 2004 and 2019, with NAC affected more. However, despite longer wait times, short-term survival increased significantly. Very short (<15 days) and very long (>75 days) TTS were associated with increased mortality risk. Patients with HPV + HNSCC have the highest increase among those treated > 75 days from diagnosis. Treatment at AC was associated with improved survival, which could be explained by the presence of multidisciplinary teams and subspecialists that may be less available at NAC. The 2021 NCDB data are required for a comprehensive analysis of wait times in 2020.

Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors.

We analyzed transcriptional data from 104 HPV+ (Human papillomavirus) HNSCC (head and neck squamous cell carcinoma) tumors together with two publicly available sources to identify highly robust transcriptional programs (modules) which could be detected consistently despite heterogeneous sequencing and quantification methodologies. Among 22 modules identified, we found a single module that naturally subclassifies HPV+ HNSCC tumors based on a bimodal pattern of gene expression, clusters all atypical features of HPV+ HNSCC biology into a single subclass, and predicts patient outcome in four independent cohorts. The subclass-defining gene set was strongly correlated with Nuclear factor kappa B (NF-κB) target expression. Tumors with high expression of this NF-κB module were rarely associated with activating PIK3CA alterations or viral integration, and also expressed higher levels of HPHPV E2 and had decreased APOBEC mutagenesis. Alternatively, they harbored inactivating alterations of key regulators of NF-κB, TNF receptor associated factor 3 (TRAF3), and cylindromatosis (CYLD), as well as retinoblastoma protein (RB1). HPV+ HNSCC cells in culture with experimental depletion of TRAF3 or CYLD displayed increased expression of the subclass-defining genes, as well as robust radio-sensitization, thus recapitulating both the tumor transcriptional state and improved treatment response observed in patient data. Across all gene sets investigated, methylation to expression correlations were the strongest for the subclass-defining, NF-κB-related genes. Increased tumor-infiltrating CD4+ T cells and increased Estrogen receptors alpha (ERα) expression were identified in NF-κB active tumors. Based on the relatively high rates of cure in HPV+ HNSCC, deintensification of therapy to reduce treatment-related morbidity is being studied at many institutions. Tumor subclassification based on oncogenic subtypes may help guide the selection of therapeutic intensity or modality for patients with HPV+ HNSCC.

Plasmacytoma of the Head and Neck: Case Series and Review of the Literature.

Solitary plasmacytoma is a rare neoplasm characterized by localized proliferation of monoclonal plasma cells and is classified as solitary bone or solitary extramedullary plasmacytoma. Here, we present two rare cases of plasmacytoma of the head and neck. The first is a 78-year-old male who presented with a 3-month history of epistaxis and progressive obstruction of the right nasal passage. Computerized tomography (CT) imaging revealed a mass in the right nasal cavity with destruction to the maxillary sinus. An excisional biopsy was performed revealing anaplastic plasmacytoma. The second is a 64-year-old male with a past medical history significant for prostate cancer who presented with a 2-month history of left ear pain and progressive non-tender temporal swelling. A PET/CT revealed a highly avid, destructive, and lytic left temporal mass with no other evidence of distant disease. A left temporal craniectomy and infratemporal fossa dissection revealed plasma cell dyscrasia with monoclonal lambda in situ hybridization. Although plasmacytomas are uncommon tumors of the head and neck, they may mimic other entities that require different treatment. Prompt and accurate diagnosis is critical for appropriate therapeutic decisions and prognosis.

Sinonasal quality of life in primary ciliary dyskinesia.

KEY POINTS: Our findings suggest that primary ciliary dyskinesia (PCD)-related chronic rhinosinusitis (CRS) has a more significant impact on quality of life than CRS without nasal polyps and cystic fibrosis (CF). PCD and CF have similar mucociliary clearance defects, yet sinonasal symptom severity varies between the two.

Granulomatosis With Polyangiitis Presenting as an Infratemporal Fossa Mass.

Granulomatosis with polyangiitis is a rare autoimmune disease that affects small to medium-sized blood vessels throughout the body. Here, we present a case of an infratemporal mass that was the result of granulomatosis with polyangiitis. A 51-year-old male presented to the emergency department due to right cheek and facial pain that he had been experiencing for 2 to 3 months. An MRI revealed a mass within the right infratemporal and pterygopalatine fossae extending into the inferior right orbital fissure along the maxillary division of the trigeminal nerve (V2) and the vidian nerve causing concern for malignancy. Histology from an endoscopic biopsy demonstrated multiple arteries with luminal obliteration with non-necrotizing granulomas. The patient was started on steroids and immunosuppressive therapy, which improved his symptoms and decreased the size of the residual mass. This case illustrates the need for laboratory testing, imaging, and biopsy of the involved tissue in cases where GPA is suspected to prevent treatment delays that could lead to the destruction of vital organs.

Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration.

Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a loss of E2. Here, we compare patterns of HPV integration in UCSCC and OPSCC by analysis of affinity capture sequencing of the HPV16 genome in 104 OPSCC and 44 UCSCC tumors. These cohorts were contemporaneously sequenced using an identical strategy. Integration was identified using discordant read pair clustering and assembly-based approaches. Viral integration sites, structural variants, and copy losses were examined. While large-scale deep losses of HPV16 genes were common in UCSCC and were associated with E2 loss, deep copy losses of the HPV16 genome were infrequent in HPV16+ OPSCC. Similarly, structural variants within HPV16 favored E2 loss in UCSCC but not OPSCC. HPV16 integration sites were non-random, with recurrent integration hot-spots identified. OPSCC tumors had many more integration sites per tumor when compared to UCSCC and had more integration sites in genomic regions with high gene density. These data show that viral integration and E2 disruption are distinct in UCSCC and OPSCC. Our findings also add to growing literature suggesting that HPV tumorigenesis in OPSCC does not follow the model developed based on UCSCC.

Effects of palmitoylation on the diffusional movement of BKCa channels in live cells.

BKCa channels are palmitoylated at a cluster of cysteine residues within the cytosolic linker connecting the 1st and 2nd transmembrane domains, and this lipid modification affects their surface expression. To verify the effects of palmitoylation on the diffusional dynamics of BKCa channels, we investigated their lateral movement. Compared to wild-type channels, the movement of mutant palmitoylation-deficient channels was much less confined and close to random. The diffusion of the mutant channel was also much faster than that of the wild type. Thus, the lateral movement of BKCa channels is greatly influenced by palmitoylation.

Relationships among advance directives, principal diagnoses, and discharge outcomes in critically ill older adults.

OBJECTIVE: The purpose of this study was to determine the relationships among advance directive status, principal diagnoses, and the discharge outcomes in community-dwelling, critically ill older adults. METHOD: Using administrative and clinical data (n = 1673), multinomial logit regressions were used to examine the relationships among advance directive status, principal diagnoses, and discharge outcomes (in-hospital deaths, hospice discharges, and transition to institutions). RESULTS: In the overall sample, the adjusted probability of in-hospital deaths with advance directives (12%) was lower than that without advance directives (17%; odds ratio [OR] = 0.56; p = 0.007) and the adjusted probability of hospice discharges with advance directives (11%) was higher than that without advance directives (7%; OR = 1.96; p = 0.03). Subgroup analysis showed that the magnitude of the abovementioned changes was aggregated when their principal diagnoses were a group of diseases with more difficult prognostication (circulatory and respiratory diseases) and more potential for reversibility (infectious diseases). By contrast, the magnitude of the abovementioned findings was diminished with other principal diagnoses. On the other hand, the presence of advance directives did not make a contribution to transition from communities to institutions. SIGNIFICANCE OF RESULTS: Significantly fewer in-hospital deaths in addition to higher hospice discharges were observed with any advance directives in community-dwelling, critically ill older adults. The magnitude of these findings was aggregated when their principal diagnoses were a group of diseases with more difficult prognostication (circulatory and respiratory diseases) and more potential for reversibility (infectious diseases). By contrast, the magnitude of these findings was diminished with other principal diagnoses.

Integrative palliative care, advance directives, and hospital outcomes of critically ill older adults.

OBJECTIVE: To examine the associations between palliative care types and hospital outcomes for patients who have or do not have advance directives. METHOD: Using administrative claims and clinical data for critically ill older adults (n = 1291), multivariable regressions examined the associations between palliative care types and hospital outcomes by advance directive status. RESULTS: Integrative palliative care was associated with lower hospital costs, lower adjusted probability of in-hospital deaths, and higher adjusted probability of hospice discharges. There was no difference in hospital outcomes by palliative care types in those with advance directives. CONCLUSION: Significantly lower hospital costs and in-hospital deaths with higher hospice discharges were observed in integrative palliative care compared to consultative palliative care, but these findings were diminished with the presence of advance directives.