A case report of sinonasal glomangiopericytoma: An important reminder to always collect specimen.

OBJECTIVES: To present a case report of sinonasal glomangiopericytoma (GPC) in a female patient in her thirties and to highlight the importance of collecting pathology specimens even in routine sinus surgery cases. METHODS: A case report detailing the diagnosis of GPC in a female in her thirties, including her initial presentation, treatment, and follow-up, along with a brief review of the literature. RESULTS: Pathology of the collected specimen revealed sinonasal GPC along with chronic rhinosinusitis. Immunohistochemistry was positive for SMA, beta-catenin, and cyclin D1; and negative for STAT6, ERG, pankeratin, SOX10, and S100. CONCLUSION: This diagnosis expands the knowledge around the demographic profile of GPC patients. GPC should be included in the differential diagnosis of sinonasal masses, even in younger patients. The case highlights the importance of collecting the entire pathology specimen in all cases, even of ones that seem routine and benign.

Early Improved Functional Outcomes in Head and Neck Cancer Patients with Primary Tumor Detection.

OBJECTIVES: We characterize functional outcomes in head and neck cancer of unknown primary (CUP) based on primary site identification. METHODS: In this retrospective study, CUP cases were categorized as known primaries (KP) if a tumor was localized after diagnostic workup or persisting unknown primaries (UP). Age, sex, HPV status, diagnostic methods, and treatments regimens were collected. Pretreatment and short-term posttreatment (3-6 months after completion of treatment) weights, PHQ-9, Eating Assessment Tool (EAT-10), and Voice Handicap Index (VHI-10) scores were compared between UP and KP. RESULTS: Among 67 CUP patients, 35 (52.2%) had identified primaries (91.4% oropharyngeal and 8.6% nasopharyngeal). KP patients were younger (58 vs. 64, p = 0.04) and more likely to be HPV-positive (88.6% vs. 50%, p = 0.002). Overall detection rates were 16.7% for PET/CT, 34.7% for direct laryngoscopy, and 46.6% for transoral robotic oropharyngectomy. Diagnostic workup was not significantly different between groups. Patients with KP received smaller intermediate radiation dose volumes (436.5 vs. 278.9 cc, p = 0.03) and lower doses to the cricopharyngeal muscle (41.6 vs. 24.6 Gy, p = 0.03).Pretreatment weights, PHQ-9, EAT-10, and VHI-10 scores did not differ between groups. However, posttreatment, UP had greater relative weight loss (-14.1% vs. -7.6%, p = 0.032), higher EAT-10 scores (12.5 vs. 3, p = 0.004), and higher PHQ-9 scores (6 vs. 1.4, p = 0.017). Specifically, UP reported more stressful swallowing, difficulty swallowing solids and pills, and swallowing affecting public eating. CONCLUSION: KP patients experienced less weight loss, depression, and reduced swallowing dysfunction, highlighting an early functional benefit of primary tumor identification likely driven by reduced radiation treatment volumes. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:701-707, 2024.

SMYD3 represses tumor-intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck.

Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of immune escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy with pembrolizumab. SMYD3 depletion induces upregulation of multiple type I interferon (IFN) response and antigen presentation machinery genes in HNSCC cells. Mechanistically, SMYD3 binds to and regulates the transcription of UHRF1, encoding for a reader of H3K9me3, which binds to H3K9me3-enriched promoters of key immune-related genes, recruits DNMT1, and silences their expression. SMYD3 further maintains the repression of immune-related genes through intragenic deposition of H4K20me3. In vivo, Smyd3 depletion induces influx of CD8+ T cells and increases sensitivity to anti-programmed death 1 (PD-1) therapy. SMYD3 overexpression is associated with decreased CD8 T cell infiltration and poor response to neoadjuvant pembrolizumab. These data support combining SMYD3 depletion strategies with checkpoint blockade to overcome anti-PD-1 resistance in HPV-negative HNSCC.

Virtual Interviewing in the Era of COVID-19: A Preliminary Analysis of Otolaryngology Residency Program Costs.

Objective: A preliminary comparison of the program experience and costs associated with the virtual interview season during the 2020-2021 COVID-19 pandemic against the traditional in-person interview process during the 2019-2020 interview season. Study Design: Cross-sectional survey. Setting: Our institutional program launched an online survey via REDCap to otolaryngology programs across the country. Methods: A 33-item survey was sent to otolaryngology residency program directors regarding their experience and costs associated with virtual interviews during the 2020-2021 cycle and in-person interviews during the previous 2019-2020 cycle. Purchasing cost and opportunity cost were calculated for each program. Results: Twenty-two programs sent back completed survey responses. Program responses were equally represented among all regions of the United States. In the 2020-2021 interview season, programs received more applications (mean, 400 vs 336 the year prior, P < .001) for a similar number of residency spots per program (3.04 in 2020-2021 vs 3.0 2019-2020, P = .715). The virtual interview led to more half-day interviews, a shorter duration of each interview, and fewer interviews completed per interview date. Purchasing cost decreased by $1940.46 (73%), and person-hours dedicated to the interview process decreased by 52.36 with the virtual interview. Total savings per program with virtual interviews were an estimated $6941.66. Conclusions: Virtual interviews in the setting of the COVID-19 pandemic led to a shift in application and interview patterns and was associated with a reduction in costs for programs when compared with the in-person interview format.

Environmental Considerations for Effective Telehealth Encounters: A Narrative Review and Implications for Best Practice.

Introduction: Due to the reduction in-person visits, the COVID-19 pandemic has led to expansions in the use of telehealth technology to provide patient care, yet clinicians lack evidence-based guidance on how to most effectively use video communication to enhance patient experience and outcomes. Methods: A narrative review was conducted to describe environmental factors derived from research in social psychology and human-computer interaction (HCI) that may guide effective video-based clinician-patient telehealth communication. Results: Factors such as nonverbal cues, spatial proximity, professionalism cues, and ambient features play an important role in patient experience. We present a visual typology of telehealth backgrounds to inform clinical practice and guide future research. Discussion: A growing body of empirical evidence indicates that environmental cues may play an essential role in establishing psychological safety, improving patient experience, and supporting clinical efficacy in these virtual experiences. Conclusion: The expanded use of telehealth visits suggests the need for further research on the relative effects of these environmental factors on patient experience and outcomes.

Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands.

Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems.

SMYD3: a regulator of epigenetic and signaling pathways in cancer.

Chromatin modifiers and their implications in oncogenesis have been an exciting area of cancer research. These are enzymes that modify chromatin via post-translational modifications such as methylation, acetylation, sumoylation, phosphorylation, in addition to others. Depending on the modification, chromatin modifiers can either promote or repress transcription. SET and MYN-domain containing 3 (SMYD3) is a chromatin modifier that has been implicated in the development and progression of various cancer types. It was first reported to tri-methylate Histone 3 Lysine 4 (H3K4), a methylation mark known to promote transcription. However, since this discovery, other histone (H4K5 and H4K20, for example) and non-histone (VEGFR, HER2, MAP3K2, ER, and others) substrates of SMYD3 have been described, primarily in the context of cancer. This review aims to provide a background on basic characteristics of SMYD3, such as its protein structure and tissue expression profiles, discuss reported histone and non-histone substrates of SMYD3, and underscore prognostic and functional implications of SMYD3 in cancer. Finally, we briefly discuss ongoing efforts to develop inhibitors of SMYD3 for future therapeutic use. It is our hope that this review will help synthesize existing research on SMYD3 in an effort to propel future discovery.

Clinicopathologic significance of protein lysine methyltransferases in cancer.

Protein lysine methyltransferases (PKMTs) constitute a large family of approximately 50 chromatin modifiers that mono-, di- and/or tri-methylate lysine residues on histone and non-histone substrates. With the advent of The Cancer Genome Atlas, it became apparent that this family of chromatin modifiers harbors frequent genetic and expression alterations in multiple types of cancer. In this regard, past and ongoing preclinical studies have provided insight into the mechanisms of action of some of these enzymes, laying the ground for the ongoing development of PKMT inhibitors as novel anticancer therapeutics. The purpose of this review is to summarize existing data obtained by different research groups through immunohistochemical analysis of the protein expression levels of PKMTs, and their respective clinicopathologic associations. We focused on studies that used immunohistochemistry to associate protein expression levels of specific PKMTs, as well as several established histone methylation marks, with clinicopathologic features and survival outcomes in various cancer types. We also review ongoing clinical trials of PKMT inhibitors in cancer treatment. This review underscores the clinical relevance and potential of targeting the family of PKMT enzymes as the next generation of cancer therapy.

Cryptic evolved melts beneath monotonous basaltic shield volcanoes in the Galápagos Archipelago.

Many volcanoes erupt compositionally homogeneous magmas over timescales ranging from decades to millennia. This monotonous activity is thought to reflect a high degree of chemical homogeneity in their magmatic systems, leading to predictable eruptive behaviour. We combine petrological analyses of erupted crystals with new thermodynamic models to characterise the diversity of melts in magmatic systems beneath monotonous shield volcanoes in the Galápagos Archipelago (Wolf and Fernandina). In contrast with the uniform basaltic magmas erupted at the surface over long timescales, we find that the sub-volcanic systems contain extreme heterogeneity, with melts extending to rhyolitic compositions. Evolved melts are in low abundance and large volumes of basalt flushing through the crust from depth overprint their chemical signatures. This process will only maintain monotonous activity while the volume of melt entering the crust is high, raising the possibility of transitions to more silicic activity given a decrease in the crustal melt flux.

WHSC1 monomethylates histone H1 and induces stem-cell like features in squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck (SCCHN) is a malignancy with poor outcomes, thus novel therapies are urgently needed. We recently showed that WHSC1 is necessary for the viability of SCCHN cells through H3K36 di-methylation. Here, we report the identification of its novel substrate, histone H1, and that WHSC1-mediated H1.4K85 mono-methylation may enhance stemness features in SCCHN cells. To identify proteins interacting with WHSC1 in SCCHN cells, WHSC1 immunoprecipitation and mass spectrometry identified H1 as a WHSC1-interacting candidate. In vitro methyltransferase assays showed that WHSC1 mono-methylates H1 at K85. We generated an H1K85 mono-methylation-specific antibody and confirmed that this methylation occurs in vivo. Sphere formation assays using SCC-35 cells stably expressing either wild-type (FLAG-H1.4-WT) or mutated (FLAG-H1.4K85A) vector with lysine 85 to alanine substitution which is not methylated, indicated a higher number of spheres in SCC-35 cells expressing the wild type than those with the mutant vector. SCC-35 cells expressing the wild type H1.4 proliferated faster than those expressing the mutated vector. RNA sequencing, RT-PCR and Western blotting of the FLAG-H1.4-WT or FLAG-H1.4K85A SCC-35 cells revealed that OCT4 levels were higher in wild type compared to mutant cells. These results were reproduced in SCC-35 cells genetically modified with CRISPR to express H1.4K85R. Chromatin immunoprecipitation showed that FLAG-H1.4K85A had decreased occupancy in the OCT4 gene compared to FLAG-H1.4-WT. This study supports that WHSC1 mono-methylates H1.4 at K85, it induces transcriptional activation of OCT4 and stemness features in SCCHN cells, providing rationale to target H1.4K85 mono-methylation through WHSC1 in SCCHN.

Metastatic prostate carcinoma to the orbit as the first presentation of disease.

Prostate carcinoma is a common tumor of the older adult male. It is associated with bony metastases, particularly to the axial skeleton. We present two case histories; in both cases, the patients had no prior history of prostate carcinoma. Both cases were diagnosed with CT imaging, elevated PSA, and biopsy. Additionally, they were treated with surgical resection and hormone modulation therapy. While bony metastases are frequently associated with advanced disease, they can also be a cause of presenting symptoms. The CT imaging in these two cases showed the classic hyperostotic findings of prostate cancer. Prostate cancer may cause osteoblastic lesions in contrast to other metastatic bone lesions, which cause destructive osteolytic lesions. During excisional surgery, the tumor was inspected and many stalactite-like lesions were present on the gross sample. We present these and compare them to the CT imaging.

Treating a Structural Heart Disease Using a Non-structural Approach: Role of Cardiac Pacing in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease characterized by a thickened non-dilated ventricle in the absence of another cardiac or systemic condition. Its most important hemodynamic consequence is left ventricular outflow tract (LVOT) obstruction. The primary management strategy of this condition is surgical septal myectomy, but an acceptable alternative treatment in patients who are not suitable for (or who refuse) surgery is alcohol septal ablation (ASA). However, in patients with unfavorable coronary anatomy which precludes ASA (i.e. absence of major septal perforator branch of the left anterior descending (LAD) artery), another reasonable option is dual chamber pacemaker implantation to decrease LVOT outflow gradient. A 77-year-old female, known hypertensive, diabetic with a history of coronary artery disease, presented with 1-week history of worsening chest pain and shortness of breath. She was admitted as a case of acute coronary syndrome and pneumonia. On workup, 2DED revealed hypertrophic obstructive cardiomyopathy (HOCM) with a demonstrated systolic anterior motion (SAM) of the mitral valve with a peak instantaneous gradient of 194 mm Hg across the basal LV cavity. The patient refused surgical myectomy, and ASA was the preferred treatment option. On coronary angiography, there was an incidental finding of absent major septal perforator branch of the LAD coronary artery, rendering her unsuitable for septal ablation. She was referred to electrophysiology for evaluation. She underwent dual chamber pacemaker implantation and documented significant decrease in the peak instantaneous gradient from 194 to 37 mm Hg, with complete obliteration of SAM and improvement in overall wall motion. She remained stable and asymptomatic after pacemaker insertion until her recent outpatient follow-up (1 year after implantation). We present a case of HCM with congenitally absent major septal perforator branch coronary artery treated with dual chamber pacemaker implantation. To our knowledge, this is the first reported angiographically absent first (major) septal perforator coronary anatomy in the setting of HCM, and also the first description of dual chamber pacemaker implantation to relieve the LVOT obstruction. Although the role of dual chamber pacing has become limited in HCM because surgical myectomy and septal ablation have resulted in better decrease in LV outflow gradient and symptom improvement, this modality remains essential and may still be considered as the treatment strategy-of-choice in patients who are unsuitable for surgical myectomy and ASA.

Development and validation of the Filipino Version of the Coronary Artery Disease Education Questionnaire Version 2 (FILIPINO CADE-Q II)

Introduction@#There is currently a lack of validated tools that measure knowledge level as an outcome of the educational component of cardiac rehabilitation programs in our local setting. The researchers aim to culturally adapt and validate a questionnaire that was designed to assess patients’ knowledge about coronary artery disease and participation in cardiac rehabilitation programs, the second version of the Coronary Artery Disease Education Questionnaire (CADE-Q II). @*Methods@#Qualified translators did two independent translations of the questionnaire. After back translation, the questions were reviewed and modified by a committee of experts. The final Filipino version was tested in a pilot study. For psychometric validation the tool was administered to 109 patients enrolled in a cardiac rehabilitation program. Criterion validity was assessed with regards to differences in educational attainment and patient characteristics. Spearman rank was used to correlate patient’s level of knowledge with number of sessions attended. Internal consistency was assessed by use of cronbach’s alpha.@*Results@#The final version of the questionnaire had 30 questions arranged in five domains consisting of medical condition, risk factors, exercise, nutrition, and psychosocial risk. Patients who were college graduates had significantly higher mean scores than non college graduates. The number of cardiac rehab sessions attended had a weak but statistically significant correlation with knowledge. (spearman rho 0.35, p=0.007). The overall internal consistency of the questionnaire was good (α=0.75)@*Conclusion@#The CADE-Q II questionnaire cross culturally adapted in Filipino is a valid and reliable tool which can be used to assess Filipino patients’ knowledge about their disease when participating in cardiac rehabilitation programs.

Farris-Tang retractor in optic nerve sheath decompression surgery.

PURPOSE: Our purpose is to introduce the use of the Farris-Tang retractor in optic nerve sheath decompression surgery. METHODS: The procedure of optic nerve sheath fenestration was reviewed at our tertiary care teaching hospital, including the use of the Farris-Tang retractor. RESULTS: Pseudotumor cerebri is a syndrome of increased intracranial pressure without a clear cause. Surgical treatment can be effective in cases in which medical therapy has failed and disc swelling with visual field loss progresses. Optic nerve sheath decompression surgery (ONDS) involves cutting slits or windows in the optic nerve sheath to allow cerebrospinal fluid to escape, reducing the pressure around the optic nerve. We introduce the Farris-Tang retractor, a retractor that allows for excellent visualization of the optic nerve sheath during this surgery, facilitating the fenestration of the sheath and visualization of the subsequent cerebrospinal fluid egress. Utilizing a medial conjunctival approach, the Farris-Tang retractor allows for easy retraction of the medial orbital tissue and reduces the incidence of orbital fat protrusion through Tenon's capsule. CONCLUSION: The Farris-Tang retractor allows safe, easy, and effective access to the optic nerve with good visualization in optic nerve sheath decompression surgery. This, in turn, allows for greater surgical efficiency and positive patient outcomes.

Sub-20-ps pulses from a passively Q-switched microchip laser at 1 MHz repetition rate.

We present a 50 µm Nd3+:YVO4 microchip laser that is passively Q-switched by a semiconductor saturable absorber mirror. To reduce handling problems caused by the small crystal dimensions, the 50 µm Nd3+:YVO4 crystal is optically bonded to an undoped YVO4 crystal of a length of about 500 µm. By using a saturable absorber mirror with an effective modulation depth of >10% the system is able to deliver 16 ps pulses at a repetition rate of up to 1.0 MHz. The average laser power is 16 mW at 1064 nm. To our knowledge these are the shortest Q-switched pulses ever reported from a solid-state laser. The limits in terms of pulse width, repetition rate, output power, and system stability are discussed. Additionally, continuous-wave behavior is analyzed. Experimental data is compared with the simulation results of the coupled rate equations.

Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine-mediated apoptosis.

We have recently shown that staurosporine (ST) can trigger apoptosis of CaSki and HeLa cervical tumor cells from G2/M checkpoint, though the mechanism remains elusive. In this study, we reported that ST induced the inhibition of E6 and E7 viral oncogene and MDM2 expression, while it led to increased levels of p53, which was transiently located to mitochondria. Additionally, the proteins of the p53-regulated genes, p21(WAF1) and Bax, were increased with a similar time, while Bcl-2 and Bcl-X(L) expression was lowered. Upon ST treatment, the cytochrome c was released into the cytosol and, then, activation of caspases-9 and -3 led to Poly(ADP)RibosePolymerase (PARP) cleavage. Finally, characteristic morphological signs confirmed the apoptosis execution. Thus, taken together, all these observations suggest that apoptosis can be reactivated in HPV-positive human carcinoma cells and highlight that ST could be used as a potently chemotherapy agent to enhance the sensitivity of tumor cells to apoptosis.