Efficacy of a programmed death-1 checkpoint inhibitor in a case of cutaneous squamous cell carcinoma harboring mutations of TP53 and BRCA2.

Immune checkpoint blockades were reported to result in clinical responses in inoperable and metastatic cutaneous squamous cell carcinoma (cSCC). This report describes an 87-year-old woman with recurrent cSCC that was initially responsive to cetuximab (the monoclonal antibody against epithelial growth factor receptor) but eventually became refractory to cetuximab and multiple subsequent salvage chemotherapy regimens. Next-generation sequencing of the tumor discovered three single-nucleotide mutations in TP53, copy number amplification in Src, and a heterozygous deletion in BRCA2. Because of the high mutation burden of her neoplasm (35.2 mutations per megabase), we treated her with a programmed death-1 (PD-1) checkpoint inhibitor, pembrolizumab, for 10 months. The tumor regressed 3 months later and complete pathological remission was achieved 10 months after starting treatment. As of writing, the patient has been disease free for 17 months after discontinuing treatment. This is the first reported case of heterozygous deletion of BRCA2 in cSCC. The high mutation burden and BRCA2 mutation might explain why this tumor was highly sensitive to anti-PD-1 treatment.

Comparison of the Physical and Electrical Properties of HfO2/Al2O3/HfO2/GeOx/Ge and HfO2/Al2O3/GeOx/Ge Gate Stacks.

A high-quality HfGeOx interfacial layer (IL) was formed in a HfO2/Al2O3/HfO2/GeOx gate stack through thermal annealing. The diffusing of GeO into the HfO2 layer led to the mixing of the GeOx and HfO2 layers, as identified through energy-dispersive X-ray Spectroscopy (EDX). X-ray photo-electron spectroscopy (XPS) data for HfGeOx IL confirmed the formation of Ge-O-Hf bonds owing to the induced shift of the Ge3dox spectra to lower binding energies. The electrical and reliability data indicated that the capacitor with HfGeOx IL presented not only lower interface states density (Dit, approximately 7 × 1011 eV-1cm-2) but also less Dit increment (approximately 3 × 1011 eV-1cm-2) after stressing than did the capacitor without the HfGeOx IL. Moreover, the Ge p-metal-oxide-semiconductor field-effect transistor HfGeOx IL exhibited a high effective hole mobility (approximately 704 cm2/V s).

Application of ultrasound-guided core biopsy to minimize the non-diagnostic results and the requirement of diagnostic surgery in extrapulmonary tuberculosis of the head and neck.

PURPOSE: Head and neck extrapulmonary tuberculosis (ETB) presenting as lymphadenopathy poses a great threat by potentially increasing the deterioration of clinical outcomes. Tissue sampling for diagnostic confirmation of ETB is the only invasive procedure during the entire clinical course. It is, therefore, necessary to establish ETB sampling methods with accuracy and minimal invasiveness. METHODS: From 2009 to 2014, consecutive patients suspected of ETB receiving ultrasound-guided core biopsy (USCB), fine needle aspiration (FNA), and open biopsy (OB) were enrolled for comparison. RESULTS: There were 52 cases in the USCB group, 58 cases in the FNA group, and 78 cases in the OB group. For USCB, FNA, and OB groups, the diagnostic rates were 84.6 %, 8.6 %, and 100 % and the positive rates of acid-fast stain were 28.6 %, 0 %, and 37.5 %, respectively. The diagnostic rates of culture were 9.6 %, 0 %, and 50 %, respectively. For head and neck ETB, USCB procedure is timesaving, without leaving poor-healing wounds, scars, and the need for general anaesthesia and hospitalization. CONCLUSIONS: This study helps to optimize the ETB sampling method in head and neck based on diagnostic accuracy and minimal invasiveness. USCB can serve as the first-line diagnostic tool for ETB by reducing non-diagnostic results and the need for diagnostic surgery. KEY POINTS: • USCB shows higher diagnostic accuracy of ETB than FNA (84.6 % vs. 8.6 %). • USCB diminishes wound complications caused by surgical intervention for ETB. • USCB avoids general anaesthesia and hospitalization for diagnosing ETB. • USCB saves time and reduces the medical costs of diagnosing ETB.

Lymphovenous Anastomosis for the External and Internal Types of Head and Neck Lymphedema: A Case Series and Preliminary Clinical Results.

Background: Head and neck lymphedema (HNL), including external and internal types, could be a possible consequence for patients who have received neck dissection and radiotherapy for head and neck cancer. Initially, the common presentations are heaviness or tightness, followed by swelling in appearance, or difficulty speaking and swallowing in internal edema cases. Lymphovenous anastomosis (LVA) is an established approach to treat extremity lymphedema. We hereby present our preliminary experience in using LVA to treat HNL. Methods: Between March 2021 and January 2024, six patients with HNL were treated with LVA via a preauricular or submandibular incision of the obstructed side. Lymphedema Symptom Intensity and Distress Surveys-Head and Neck (LSIDS-H&N) were used for evaluation. In addition, for the external type, MD Anderson Cancer Center Head and Neck Lymphedema (MDACC HNL) rating scale was used for evaluation. For the internal type, Swallowing Quality of Life was used for evaluation. Results: With an average follow-up period of 15.4 ±â€…15.9 months, LSIDS-H&N improved from 1.11 ±â€…0.54 to 0.44 ±â€…0.66 (P = 0.02). For patients with the external type, within an average follow-up period of 15 ±â€…16.1 months, the MDACC HNL rating scale improved from level 2 to 0 or 1a (P = 0.008). For patients with the internal type, within an average follow-up period of 21 ±â€…17.3 months, Swallowing Quality of Life improved from 130.5 ±â€…9.2 to 151 ±â€…19.8 (P = 0.5). Conclusions: Based on our preliminary results, LVA could be a potential solution to both external and internal HNL.

Evaluation of Upper Airway in Children with Obstructive Sleep Apnea Using Cone-Beam Computed Tomography.

OBJECTIVE: Cone-beam computed tomography (CBCT) offers three-dimensional structures in assessing upper airway of patients. This study aims to compare the cone-beam computerized tomography scan measurements between children with obstructive sleep apnea (OSA) and primary snoring. STUDY DESIGN: Case-control study. METHODS: This prospective study was conducted in a tertiary referral center. Thirty-six children with moderate-to-severe OSA (with apnea-hypopnea index [AHI] > 5 events/hour) and 36 age-, gender-, and obesity-matched children with primary snoring (AHI <1) were enrolled. The measurements in CBCT parameters were compared between children with moderate-to-severe OSA and primary snorers by conditional logistic regression model. RESULTS: A total of 72 children (mean age, 7.9 ± 2.8 years; 64% male) were included. Children with moderate-to-severe OSA had a significantly smaller nasopharyngeal (2900 ± 1400 vs. 3800 ± 1800 mm3 , P = .017) and oropharyngeal airway volume (5600 ± 2700 vs. 7400 ± 4000 mm3 , P = .026) than those with primary snoring. Children with moderate-to-severe OSA, as compared to primary snorers, also had a significantly smaller minimal airway area in nasopharynx (77.4 ± 37.7 vs. 107.7 ± 52.0 mm2 , P = .006) and oropharynx (66.6 ± 61.9 vs. 101.6 ± 65.8 mm2 , P = .023). Moreover, the airway length was not significantly different between children with moderate-to-severe OSA and primary snoring. CONCLUSIONS: The three-dimensional CBCT airway analysis could be used as a useful tool to evaluate upper airway in children with OSA. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:680-685, 2021.

Using Graphene-Based Composite Materials to Boost Anti-Corrosion and Infrared-Stealth Performance of Epoxy Coatings.

Corrosion prevention and infrared (IR) stealth are conflicting goals. While graphene nanosheets (GN) provide an excellent physical barrier against corrosive agent diffusion, thus lowering the permeability of anti-corrosion coatings, they have the side-effect of decreasing IR stealth. In this work, the anti-corrosion properties of 100-µm-thick composite epoxy coatings with various concentrations (0.01-1 wt.%) of GN fillers thermally reduced at different temperatures (300 °C, 700 °C, 1100 °C) are first compared. The performance was characterized by potentiodynamic polarization scanning, electrochemical impedance spectroscopy, water contact angle and salt spray tests. The corrosion resistance for coatings was found to be optimum at a very low filler concentration (0.05 wt.%). The corrosion current density was 4.57 × 10-11 A/cm2 for GN reduced at 1100 °C, showing no degradation after 500 h of salt-spray testing: a significant improvement over the anti-corrosion behavior of epoxy coatings. Further, to suppress the high IR thermal signature of GN and epoxy, Al was added to the optimized composite at different concentrations. The increased IR emissivity due to GN was not only eliminated but was in fact reduced relative to the pure epoxy. These optimized coatings of Al-GN-epoxy not only exhibited greatly reduced IR emissivity but also showed no sign of corrosion after 500 h of salt spray test.

Lateral medullary syndrome in a woman after ovulation induction.

Although atherothrombotic complications due to ovulation induction are well known in the literature, there is no previous report specifically on the presentation of a lateral medullary infarction. Recently, we have encountered a 36 years old woman with primary infertility having acute vertiginous attack after ovulation induction. Audiovestibular test battery revealed bilateral normal hearing, bilateral gaze nystagmus, rebound nystagmus beating toward the right side, loss of visual suppression with augmentation of caloric nystagmus in light on the left side, and delayed vestibular evoked myogenic potentials on the left side, which was subsequently confirmed as lateral medullary syndrome by MRI scan. In this patient, polycystic ovary syndrome plus high levels of follicle stimulating hormone (FSH) and estrogen, together with S protein deficiency may precipitate the occurrence of lateral medullary infarct after ovulation induction. Thus, in vitro fertilization treatment protocol has been terminated.

The application of ultrasound in detecting lymph nodal recurrence in the treated neck of head and neck cancer patients.

Early detection of neck lymph node (LN) recurrence is paramount in improving the prognosis of treated head and neck cancer patients. Ultrasound (US) with US-guided fine needle aspiration (FNA) and core needle biopsy (CNB) have been shown to have great accuracy for LN diagnoses in the untreated neck. However, in the treated neck with fibrosis, their roles are not clarified. Here, we retrospectively review 153 treated head and neck cancer patients who had received US and US-guided FNA/CNB. In multivariate logistic regression analyses, size (short-axis diameter >0.8 cm) (odds ratio (OR) 4.19, P = 0.007), round shape (short/long axis ratio >0.5) (OR 3.44, P = 0.03), heterogeneous internal echo (OR 3.92, P = 0.009) and irregular margin (OR 7.32, P < 0.001) are effective US features in predicting recurrent LNs in the treated neck. However, hypoechogenicity (OR 2.38, P = 0.289) and chaotic/absent vascular pattern (OR 3.04, P = 0.33) are ineffective. US-guided FNA (sensitivity/specificity: 95.24%/97.92%) is effective in the treated neck, though with high non-diagnostic rate (29.69%). US-guided CNB (sensitivity/specificity: 84.62%/100%) is also effective, though with low negative predictive value (62.5%). Overall, US with US-guided FNA/CNB are still effective diagnostic tools for neck nodal recurrence surveillance.

Application of Ultrasound-Guided Core Biopsy to Minimal-Invasively Diagnose Supraclavicular Fossa Tumors and Minimize the Requirement of Invasive Diagnostic Surgery.

Tumors of the supraclavicular fossa (SC) is clinically challenging because of anatomical complexity and tumor pathological diversity. Because of varied diseases entities and treatment choices of SC tumors, making the accurate decision among numerous differential diagnoses is imperative. Sampling by open biopsy (OB) remains the standard procedure for pathological confirmation. However, complicated anatomical structures of SC always render surgical intervention difficult to perform. Ultrasound-guided core biopsy (USCB) is a minimally invasive and office-based procedure for tissue sampling widely applied in many diseases of head and neck. This study aims to evaluate the clinical efficacy and utility of using USCB as the sampling method of SC tumors. From 2009 to 2014, consecutive patients who presented clinical symptoms and signs of supraclavicular tumors and were scheduled to receive sampling procedures for diagnostic confirmation were recruited. The patients received USCB or OB respectively in the initial tissue sampling. The accurate diagnostic rate based on pathological results was 90.2% for USCB, and 93.6% for OB. No significant difference was noted between USCB and OB groups in terms of diagnostic accuracy and the percentage of inadequate specimens. All cases in the USCB group had the sampling procedure completed within 10  minutes, but not in the OB group. No scars larger than 1  cm were found in USCB. Only patients in the OB groups had the need to receive general anesthesia and hospitalization and had scars postoperatively. Accordingly, USCB can serve as the first-line sampling tool for SC tumors with high diagnostic accuracy, minimal invasiveness, and low medical cost.

Associations between adenotonsillar hypertrophy, age, and obesity in children with obstructive sleep apnea.

OBJECTIVE: To investigate the contributions of adenoid and tonsil size to childhood obstructive sleep apnea (OSA) and the interactions between adenotonsillar hypertrophy, age, and obesity in children with OSA. METHODS: In total, 495 symptomatic patients were recruited. The patients were assigned to four groups according to age: toddler (age 1-3, n=42), preschool (age 3-6, n=164), school (age 6-12, n=200), and adolescence (age 12-18, n=89). All subjects had tonsil size graded by otolaryngologists, adenoid size determined on lateral radiographs (Fujioka method), and a full-night polysomnography. The apnea-hypopnea index (AHI), adenoid size, and tonsil size were compared in obese and non-obese children in the four age groups. Adjusted odds ratios (ORs) and 95% confidence interval (CI) of adenotonsillar hypertrophy and OSA risk were estimated by multi-logistic regression. RESULTS: The AHI was positively related to tonsil grade (r=0.33, p <0.001) and adenoid size (r=0.24, p <0.01) in all patients. Tonsil grade was positively related to AHI in all four age groups. Adenoid size was positively related to AHI in the toddler, preschool, school groups, but not in the adolescent group (r=0.11, p=0.37). Tonsil grade and adenoid size were both positively related to AHI in obese and non-obese children. In the regression model, obesity (OR=2.89; 95% CI 1.47-5.68), tonsillar hypertrophy (OR=3.15; 95% CI 2.04-4.88), and adenoidal hypertrophy (OR=1.89; 95% CI 1.19-3.00) significantly increased OSA risk. CONCLUSIONS: Adenotonsillar hypertrophy and obesity are the major determinants of OSA in children. However, the influence of adenoid size decreases in adolescence.

Ocular vestibular-evoked myogenic potentials via bone-conducted vibration in children.

OBJECTIVE: This study utilized bone-conducted vibration (BCV) stimuli for eliciting ocular vestibular-evoked myogenic potentials (oVEMPs) to assess the vestibulo-ocular reflex (VOR) system in healthy children and adults. METHODS: Fifteen healthy children aged 3-14 years and 18 healthy adults aged 24-28 years underwent oVEMP testing. Structural factors such as body weight, body height and body mass index were measured for each healthy subject. RESULTS: All healthy children and adults presented clear oVEMPs, bilaterally. The characteristic parameters (latencies and amplitude) of oVEMPs did not significantly differ between children and adults. The mean interaural (y-axis) acceleration magnitudes for eliciting oVEMPs were 0.37 ± 0.12 g for children and 0.41 ± 0.20 g for adults, a non-significant difference. As stimulation intensity increased stepwise, interaural acceleration magnitude increased correspondingly, leading to early nI latency and large nI-pI amplitude of oVEMPs. However, no structural factor was statistically correlated with interaural acceleration magnitude. CONCLUSION: When children aged >3 years, the simple and quick oVEMP test via BCV stimulation can be used for investigating the integrity of the VOR system, with the characteristic parameters (latencies and amplitude) unaffected by structural factors. SIGNIFICANCE: Establishing the norm of oVEMP is essential for diagnosing VOR deficit in children aged >3 years.

Aging effect on the ocular vestibular-evoked myogenic potentials.

OBJECTIVE: This study applied ocular vestibular-evoked myogenic potential (oVEMP) tests in healthy subjects of various ages to measure the effect of aging on oVEMPs quantitatively. STUDY DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Seventy healthy subjects with the ages ranging from 24 to 76 years were divided into 6 groups by decade. Each group consisted of 10 subjects in 1 decade except 20 subjects in the group of 60 to 69 years. MAIN OUTCOME MEASURES: All subjects underwent oVEMP tests using bone-conducted vibration stimuli. RESULTS: All subjects in groups of 20-59 years showed 100% response rates of clear oVEMPs, while 22 (55%) of 40 eyes in group of 60-69 years and 8 (40%) of 20 eyes in group of >or= 70 years had clear oVEMPs, exhibiting significant differences between those below and over 60 years of age. The mean nI and pI latencies also showed significantly prolonged in those over 60 years, whereas the mean nI-pI amplitude reduced significantly in subjects over 40 years. However, the asymmetry ratios of oVEMPs did not differ significantly among the age groups. Analyses between the age factor and characteristic parameters revealed that significant correlations existed between the age factor and the nI latency, pI latency and nI-pI amplitude, but not the nI-pI interval. CONCLUSION: Aging effect (> 60 years old) on the oVEMPs includes reduced response rate, prolonged nI and pI latencies, and decreased nI-pI amplitude. Thus, age factor should be taken into consideration when interpreting the oVEMP results.

Feasibility of the simultaneous ocular and cervical vestibular-evoked myogenic potentials in unilateral vestibular hypofunction.

OBJECTIVE: This study compared the results of combined and individual ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests in healthy subjects and patients with unilateral vestibular hypofunction to confirm the effectiveness of the combined oVEMP and cVEMP test. METHODS: Twenty healthy volunteers and 12 patients with unilateral vestibular hypofunction underwent individual oVEMP and cVEMP tests in a random order, and combined oVEMP and cVEMP test on another day. RESULTS: Twenty healthy subjects had 100% response rates for oVEMPs and cVEMPs in both individual and combined stimulation modes. Significant positive correlations exist between individual and combined oVEMPs/cVEMPs in terms of latencies and amplitudes. In 12 patients with unilateral vestibular hypofunction, differences in abnormal percentages of oVEMPs or cVEMPs were non-significant. Additionally, the characteristic parameters of oVEMP/cVEMP among ears of healthy subjects, good and pathological ears of patients with unilateral vestibular hypofunction did not differ significantly, regardless of whether the individual or combined mode was used. CONCLUSIONS: The combined oVEMP and cVEMP test generates similar information to that obtained by individual mode, regardless of whether subjects are healthy or have unilateral vestibular hypofunction. SIGNIFICANCE: Simultaneous oVEMP and cVEMP tests may be a convenient screening tool for assessing crossed vestibulo-ocular reflex and ipsilateral sacculo-collic reflex, which definitely shortens the diagnostic test time. Thus, it may favor the large diffusion of these techniques.