High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy.

BACKGROUND AND AIMS: Accurate biomarkers to predict outcomes following discontinuation of nucleos(t)ide analogue (NA) therapy are needed. We evaluated serum hepatitis B core-related antigen (HBcrAg) level as a biomarker for predicting outcomes after NA discontinuation. METHODS: Patients with HBeAg-negative chronic hepatitis B (CHB) without cirrhosis were enrolled in a prospective trial evaluating clinical outcomes until 96 weeks after NA discontinuation. End of treatment (EOT) and off-treatment levels of serum HBcrAg, HBsAg, HBV RNA and HBV DNA were used to predict key clinical outcomes including hepatitis flare (ALT ≥5 × ULN and HBV DNA > 2000 IU/mL). The SCALE-B score was calculated for the purposes of model validation. RESULTS: HBcrAg was tested amongst 65 participants. The median age was 54 years, 54% were male and 83% were Asian. HBcrAg was detectable in 86% patients. HBcrAg level ≥4 log U/mL at EOT was predictive of hepatitis flare [8/10 (80%) vs. 17/55 (31%), p = .001]. The presence of either HBcrAg ≥4 log U/mL or detectable HBV RNA at EOT predicted for both biochemical relapse and hepatitis flare. The SCALE-B model at EOT predicted for virological relapse, biochemical relapse, hepatitis flare and HBsAg loss in this cohort. An increase in the serum HBcrAg level off-treatment was also associated with hepatitis flare. No participant with EOT HBcrAg level ≥4 log U/mL achieved HBsAg loss. CONCLUSIONS: High levels of serum HBcrAg predict for hepatitis flare after stopping NA therapy and low likelihood of HBsAg loss at week 96. People with high levels of serum HBcrAg are not suitable candidates for NA discontinuation.

Peroxidase-encapsulated Zn/Co-zeolite imidazole framework nanosheets on ZnCoO nanowire array for detecting H2O2 derived from mitochondrial superoxide anion.

In this work, we have developed a nanocomposite consisting of horseradish peroxidase (HRP)-encapsulated 2D Zn-Co zeolite imidazole framework (ZIF) nanosheets strung on a ZnCoO nanowire array on a Ti support (denoted as 2D-Zn/Co-ZIF(HRP)|ZnCoO|Ti). This nanocomposite was then applied to constructing an electrochemical biosensor for detecting H2O2 derived from O2∙- released by mitochondria in living cells. This sensing platform shows excellent catalytic performance towards H2O2, attributable to the enzyme/metal-catalytic effect of HRP and Zn/Co-ZIF. The unique nano-string structure alleviates the aggregation of Zn/Co-ZIF nanosheets, readily exposes the catalytic active sites, protects the bioactivity of HRP, and reduces the charge/mass transfer pathway within Zn/Co-ZIF. The 2D-Zn/Co-ZIF(HRP)|ZnCoO|Ti biosensor offers two linear ranges of 0.2-10 µ M and 10-1100 µ M, a limit of detection of 0.082 µ M, a sensitivity of 3.3 mA mM-1 cm-2, good selectivity and stability over 40 days for H2O2 detection. After treating with specific mitochondrial complex inhibitors, the chronoamperometric results at the 2D-Zn/Co-ZIF(HRP)|ZnCoO|Ti confirmed complex I and III within the mitochondria electron transfer chain as the main electron leakage sites. This biosensor may contribute to the development of diagnostic health-care devices that shed light on the precaution and even treatment of oxidative stress diseases.

A High-Performance Hybrid Biofuel Cell with a Honeycomb-Like Ti3 C2 Tx /MWCNT/AuNP Bioanode and a ZnCo2 @NCNT Cathode for Self-Powered Biosensing.

This work focusses on developing a hybrid enzyme biofuel cell-based self-powered biosensor with appreciable stability and durability using murine leukemia fusion gene fragments (tDNA) as a model analyte. The cell consists of a Ti3 C2 Tx /multiwalled carbon nanotube/gold nanoparticle/glucose oxidase bioanode and a Zn/Co-modified carbon nanotube cathode. The bioanode uniquely exhibits strong electron transfer ability and a high surface area for the loading of 1.14 × 10-9  mol cm-2 glucose oxidase to catalyze glucose oxidation. Meanwhile, the abiotic cathode with a high oxygen reduction reaction activity negates the use of conventional bioenzymes as catalysts, which aids in extending the stability and durability of the sensing system. The biosensor offers a 0.1 fm-1 nm linear range and a detection limit of 0.022 fm tDNA. Additionally, the biosensor demonstrates a reproducibility of ≈4.85% and retains ≈87.42% of the initial maximal power density after a 4-week storage at 4 °C, verifying a significantly improved long-term stability.

Fluoride Content of Ready-to-Eat Infant Foods and Drinks in Australia.

The use of fluoride is effective in preventing dental caries. However, an excessive intake of fluoride leads to dental fluorosis, making it necessary to regularly monitor the fluoride intake especially for infants. There is hitherto a lack of information on fluoride content in infant foods from an Australian perspective. Therefore, this study aims to estimate the amount of fluoride content from a range of commercially available ready-to-eat (RTE) infant foods and drinks available in Australia. Based on an external calibration method, potentiometry involving a fluoride ion selective electrode and a silver|silver chloride reference electrode was conducted to analyse the fluoride content of a total of 326 solid food samples and 49 liquid food samples in this work. Our results showed an overall median (range) fluoride content of 0.16 (0.001-2.8) µg F/g of solid food samples, and 0.020 (0.002-1.2) µg F/mL of liquid food samples. In addition, ~77.5% of the liquid samples revealed a fluoride content < 0.05% µg F/mL. The highest variation of fluoride concentration (0.014-0.92 µg F/g) was found in formulas for ≥6 month-old infants. We have attributed the wide fluoride content variations in ready-to-eat infant foods and drinks to the processing steps, different ingredients and their origins, including water. In general, we found the fluoride content in most of the collected samples from Australian markets to be high and may therefore carry a risk of dental fluorosis. These results highlight the need for parents to receive appropriate information on the fluoride content of ready-to-eat infant food and drinks.

Fragmentomics of urinary cell-free DNA in nuclease knockout mouse models.

Urinary cell-free DNA (ucfDNA) is a potential biomarker for bladder cancer detection. However, the biological characteristics of ucfDNA are not well understood. We explored the roles of deoxyribonuclease 1 (DNASE1) and deoxyribonuclease 1-like 3 (DNASE1L3) in the fragmentation of ucfDNA using mouse models. The deletion of Dnase1 in mice (Dnase1-/-) caused aberrations in ucfDNA fragmentation, including a 24-fold increase in DNA concentration, and a 3-fold enrichment of long DNA molecules, with a relative decrease of fragments with thymine ends and reduction of jaggedness (i.e., the presence of single-stranded protruding ends). In contrast, such changes were not observed in mice with Dnase1l3 deletion (Dnase1l3-/-). These results suggested that DNASE1 was an important nuclease contributing to the ucfDNA fragmentation. Western blot analysis revealed that the concentration of DNASE1 protein was higher in urine than DNASE1L3. The native-polyacrylamide gel electrophoresis zymogram showed that DNASE1 activity in urine was higher than that in plasma. Furthermore, the proportion of ucfDNA fragment ends within DNase I hypersensitive sites (DHSs) was significantly increased in Dnase1-deficient mice. In humans, patients with bladder cancer had lower proportions of ucfDNA fragment ends within the DHSs when compared with participants without bladder cancer. The area under the curve (AUC) for differentiating patients with and without bladder cancer was 0.83, suggesting the analysis of ucfDNA fragmentation in the DHSs may have potential for bladder cancer detection. This work revealed the intrinsic links between the nucleases in urine and ucfDNA fragmentomics.

Amplified detection signal at a photoelectrochemical aptasensor with a poly(diphenylbutadiene)-BiOBr heterojunction and Au-modified CeO2 octahedrons.

A major aspect of this work is the synergistic application of a poly(diphenylbutadiene)-BiOBr composite and a gold nanoparticle-linked CeO2 octahedron to develop a photoelectrochemical aptasensor with an easily measurable detection signal change. Specifically, poly(diphenylbutadiene) nanofiber-immobilised BiOBr flower-like microspheres were developed as a hybrid material with a heterojunction that facilitates high visible light absorption and efficient photo-generated charge separation, which are essential features for sensitive photoelectrochemical sensors. The model analyte acetamiprid was attached via its specific aptamer on the aptasensor. Separately, a gold nanoparticle-linked CeO2 octahedron was strategically used to significantly diminish the photocurrent by impeding electron transfer at the aptasensor surface. After acetamiprid binding, the CeO2 octahedrons were displaced from the aptasensor. This caused a weakened quenching effect and restored the photocurrent to accomplish an "on-off-on" detection mechanism. This photoelectrochemical aptasensor exhibited a detection limit of 0.05 pM over a linear range of 0.1 pM-10 µM acetamiprid. The use of an aptamer has provided good specificity to acetamiprid and anti-interference. In addition, an ∼5.8% relative standard deviation was estimated as the reproducibility of the photoelectrochemical aptasensor. Furthermore, nearly 90% of the initial photocurrent was still measurable after storing these aptasensors at room temperature for 4 weeks, demonstrating their stability.

Nuclease deficiencies alter plasma cell-free DNA methylation profiles.

The effects of DNASE1L3 or DNASE1 deficiency on cell-free DNA (cfDNA) methylation were explored in plasma of mice deficient in these nucleases and in DNASE1L3-deficient humans. Compared to wild-type cfDNA, cfDNA in DNASE1L3-deficient mice was significantly hypomethylated, while cfDNA in DNASE1-deficient mice was hypermethylated. The cfDNA hypomethylation in DNASE1L3-deficient mice was due to increased fragmentation and representation from open chromatin regions (OCRs) and CpG islands (CGIs). These findings were absent in DNASE1-deficient mice, demonstrating the preference of DNASE1 to cleave in hypomethylated OCRs and CGIs. We also observed a substantial decrease of fragment ends at methylated CpGs in the absence of DNASE1L3, thereby demonstrating that DNASE1L3 prefers to cleave at methylated CpGs. Furthermore, we found that methylation levels of cfDNA varied by fragment size in a periodic pattern, with cfDNA of specific sizes being more hypomethylated and enriched for OCRs and CGIs. These findings were confirmed in DNASE1L3-deficient human cfDNA. Thus, we have found that nuclease-mediated cfDNA fragmentation markedly affects cfDNA methylation level on a genome-wide scale. This work provides a foundational understanding of the relationship between methylation, nuclease biology, and cfDNA fragmentation.

Detection signal amplification strategies at nanomaterial-based photoelectrochemical biosensors.

This review focusses on unique material modification and signal amplification strategies reported in developing photoelectrochemical (PEC) biosensors with utmost sensitivity and selectivity. These successes have partly been achieved by applying photoactive materials that significantly circumvent major limitations including poor absorption of visible light, severe aggregation of nanostructures, easy charge recombination and low conductivity. In addition, several signal enhancement techniques were also demonstrated to have effectively improved the detection performance of PEC biosensors. Accordingly, we have begun this review with a systematic introduction of the concept, working principle, and characteristics of PEC biosensors. This was followed by a discussion of a range of material modification techniques, including quantum dot modification, metal/non-metal ion doping, the formation of heterojunctions and Z-scheme composites, used in the construction of PEC biosensors. Various signal amplification strategies including quantum dot sensitisation, the application of electron donors, energy transfer effect, steric hindrances of biomolecules, and the exfoliation of biomolecules from sensing surfaces are also presented in this review. Wherever possible, we have referred to relevant examples to explain and illustrate the corresponding working mechanism and effectiveness of the nanomaterials. Therefore, this review is aimed at providing an overall view on the current trend in material modification and signal amplification strategies for the development of PEC biosensors, which will aid in stimulating ideas for future progress in this field.

Amplified oxygen reduction signal at a Pt-Sn-modified TiO2 nanocomposite on an electrochemical aptasensor.

In this work, a metallic composite with strong electrocatalytic property was designed by uniformly decorating Pt and Sn nanoparticles on the surface of TiO2 nanorods (Pt-Sn@TiO2). A detection scheme was then developed based on a dual signal amplification strategy involving the Pt-Sn@TiO2 composite and exonuclease assisted target recycling. The Pt-Sn@TiO2 composite exhibited an enhanced oxygen reduction current owing to the synergistic effect between Pt and Sn, as well as high exposure of Pt (111) crystal face. Initially, a Pt-Sn@TiO2 modified glassy carbon electrode produced an amplified electrochemical signal for the reduction of dissolved oxygen in the analyte solution. Next, a DNA with a complementary sequence to a streptomycin aptamer (cDNA) was immobilised on the Pt-Sn@TiO2 modified electrode, followed by the streptomycin aptamer that hybridised with cDNA. The corresponding oxygen reduction current was diminished by 51% attributable to the hindrance from the biomolecules. After a mixture of streptomycin and RecJf exonuclease was introduced, both the streptomycin-aptamer complex and the cDNA were cleaved from the electrode, making the Pt-Sn and Pt (111) surface available for oxygen reduction. RecJf would also release streptomycin from the streptomycin-aptamer complex, allowing it to complex again with aptamers on the electrode. This has then promoted a cyclic amplification of the oxygen reduction current by 85%, which is quantitatively related to streptomycin. Under optimal conditions, the aptasensor exhibited a linear range of 0.05-1500 nM and a limit of detection of 0.02±0.0045 nM streptomycin. The sensor was then used in the real-life sample detection of streptomycin to demonstrate its potential applications to bioanalysis.

A photoelectrochemical aptasensor based on a 3D flower-like TiO2-MoS2-gold nanoparticle heterostructure for detection of kanamycin.

In this work, a sensitive photoelectrochemical aptasensor was developed for kanamycin detection using an enhanced photocurrent response strategy, which is based on the surface plasmon resonance effect of gold nanoparticles deposited on a 3D TiO2-MoS2 flower-like heterostructure. A significant aspect of this development lies in the photoelectrochemical and morphological features of the unique ternary composite, which have contributed to the excellent performance of the sensor. To develop an aptasensor, mercapto-group modified aptamers were immobilised on the photoactive composite as a recognition unit for kanamycin. The TiO2-MoS2-AuNP composite was demonstrated to accelerate the electron transfer, increase the loading of aptamers and improve the visible light excitation of the sensor. Under optimal conditions, the aptasensor exhibited a dynamic range from 0.2 nM to 450 nM of kanamycin with a detection limit of 0.05 nM. Overall, we have successfully synergised both the electrical and the optical merits from individual components to form a ternary composite, which was then demonstrated as an effective scaffold for the development of PEC biosensors.

A TiO2 nanosheet-g-C3N4 composite photoelectrochemical enzyme biosensor excitable by visible irradiation.

In this work, g-C3N4 and TiO2 nanosheets were synergistically employed as a novel composite for developing a scaffold of a photoelectrochemical enzyme biosensor. In this way, we have improved the poor visible light excitation of TiO2 and retarded the photo-generated charge recombination on g-C3N4 to achieve an enhanced response at the photoelectrochemical biosensor, compared to that generated by the corresponding biosensors consisting of each individual component. Using glucose oxidase as a model enzyme, the biosensor was demonstrated to show strong visible light activity towards the enzyme mediated glucose oxidation. We have also observed a 350% enhanced photocurrent compared to that at a g-C3N4 based ITO electrode. In addition, the high specific surface area and excellent biocompatibility of TiO2 nanosheets have also positively contributed to the performance of the photoelectrochemical enzyme biosensor with a 0.05-16 mM linear range and a 0.01 mM glucose detection limit.

An intimately bonded titanate nanotube-polyaniline-gold nanoparticle ternary composite as a scaffold for electrochemical enzyme biosensors.

In this work, titanate nanotubes (TNTs), polyaniline (PANI) and gold nanoparticles (GNPs) were assembled to form a ternary composite, which was then applied on an electrode as a scaffold of an electrochemical enzyme biosensor. The scaffold was constructed by oxidatively polymerising aniline to produce an emeraldine salt of PANI on TNTs, followed by gold nanoparticle deposition. A novel aspect of this scaffold lies in the use of the emeraldine salt of PANI as a molecular wire between TNTs and GNPs. Using horseradish peroxidase (HRP) as a model enzyme, voltammetric results demonstrated that direct electron transfer of HRP was achieved at both TNT-PANI and TNT-PANI-GNP-modified electrodes. More significantly, the catalytic reduction current of H2O2 by HRP was ∼75% enhanced at the TNT-PANI-GNP-modified electrode, compared to that at the TNT-PANI-modified electrode. The heterogeneous electron transfer rate constant of HRP was found to be ∼3 times larger at the TNT-PANI-GNP-modified electrode than that at the TNT-PANI-modified electrode. Based on chronoamperometric detection of H2O2, a linear range from 1 to 1200 µM, a sensitivity of 22.7 µA mM(-1) and a detection limit of 0.13 µM were obtained at the TNT-PANI-GNP-modified electrode. The performance of the biosensor can be ascribed to the superior synergistic properties of the ternary composite.

Longitudinal profiles of highly sensitive hepatitis B surface antigen levels: re-evaluation of HBsAg seroclearance.

BACKGROUND & AIMS: Serologic profiles after hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) have not been well-studied. METHODS: We employed a highly sensitive HBsAg (hs-HBsAg) assay (lower detection limit 0.5 mIU/ml), 100 times more sensitive than conventional HBsAg measurements. CHB patients achieving HBsAg seroclearance defined by conventional assays were followed up for serum hs-HBsAg, HBV DNA and antibody to HBsAg (anti-HBs) levels at 0 months, 6-12 months and 3-5 years after HBsAg seroclearance. Factors associated with hs-HBsAg detectability were determined. RESULTS: One hundred and nine patients were recruited; 94 (86.2%) were followed up to years 3-5; and 25 patients (22.9%) were on nucleoside analogue therapy for a median duration of 6.0 (range 1.5-12.7) years before HBsAg seroclearance. Detectable hs-HBsAg was noted in 88 (80.7%), 60 (55.0%) and 20 (21.3%) patients at 0 months, 6-12 months and 3-5 years respectively. At years 3-5, genotype B patients, when compared to genotype C patients, had a higher anti-HBs positive rate (63.2% and 41.1% respectively, P = 0.036). Serum anti-HBs positivity, when compared to persistent anti-HBs negativity, was associated with a lower rate of hs-HBsAg detection (7.4% and 40% respectively, P < 0.001). Multivariate analysis showed anti-HBs negativity at years 3-5 to be independently associated with persistently positive hs-HBsAg (P = 0.007, odds ratio 7.1, 95% confidence interval 1.7-29.3). CONCLUSION: Serum hs-HBsAg could detect HBsAg presence in a substantial proportion of CHB after HBsAg seroclearance defined by conventional assays, especially among anti-HBs negative individuals. Serum hs-HBsAg could potentially assist differentiating HBsAg-negative CHB from individuals with only past HBV exposure without carrier state.

Kinetic model and thermodynamic study of Acid Red 1 entrapment at electropolymerised polypyrrole films.

This work is focussed on the determination of a kinetic model and the thermodynamic study of the electrochemical entrapment of the model azo dye, Acid Red 1, at conducting polypyrrole films, which is proposed as a potential green technology for treatment of azo dyes in industrial effluents. The entrapment kinetic data were found to follow a pseudosecond order model involving an intra-particle diffusion. However, the equilibrium data obtained for Acid Red 1 entrapment at polypyrrole did not obey any common surface adsorption models such as the Langmuir, Freundlich, Temkin and Dubinin-Radushkevich isotherms. Accordingly, the entrapment process may lead to an enhanced quantity of dye embedded in a polypyrrole film, making it a more effective and efficient technology than those involving only adsorption. Similarly, dye leakage from polypyrrole film surface to a sample matrix will be easily prevented. For this treatment process, a negative ΔG° range between -1.46±0.78 and -2.94±0.24 kJ mol(-1) at the corresponding temperature range of 298-318 K, and a ΔH° of 20.5±2.5 kJ mol(-1) indicate a spontaneous and endothermic entrapment process. Also, a positive ΔS° (73.6±8.2 J mol(-1) K(-1)) reveals increased randomness of the interface and an affinity of Acid Red 1 towards polypyrrole films. A low activation energy (7.67±0.80 kJ mol(-1)) confirms a physical process for Acid Red 1 entrapment at polypyrrole films.

Evaluation of a carbon nanotube-titanate nanotube nanocomposite as an electrochemical biosensor scaffold.

A significant aspect of this work is the development of a multi-wall carbon nanotube (MWCNT)-titanate nanotube (TNT) nanocomposite to serve as a biocompatible scaffold with high conductivity on a biosensor surface. Unlike other scaffolds consisting of MWCNTs alone or TNTs alone, the MWCNT-TNT nanocomposite synergistically provides excellent biocompatibility, good electrical conductivity, low electrochemical interferences and a high signal-to-noise ratio. For comparison, after characterising a scaffold consisting of MWCNTs alone, TNTs alone and a MWCNT-TNT nanocomposite using several spectroscopic techniques, the analytical performance of a horseradish peroxidase (HRP) electrochemical biosensor was evaluated using cyclic voltammetry and differential pulse voltammetry. The scaffold consisting of MWCNTs alone displayed a high background charging current, a low signal-to-noise ratio and distinct electrochemical interference from its surface functional groups. In contrast, the direct electrochemistry and the catalytic capability of HRP at MWCNT-TNT modified biosensors towards H2O2 was demonstrated to be ~51% and ~144% enhanced, respectively, compared to those at TNT modified biosensors. Meanwhile, MWCNT-TNT nanocomposite modified HRP biosensors also exhibited higher sensitivity (4.42µAmM(-1)) than TNT modified HRP biosensors (1.48µAmM(-1)). The above superior performance was attributed to the improved properties of MWCNT-TNT nanocomposite as biosensor scaffold compared to its two individual components by complementing each component and synergistically sustaining the characteristic features of each component.

Conducting polypyrrole films as a potential tool for electrochemical treatment of azo dyes in textile wastewaters.

In this paper, we demonstrate conducting polypyrrole films as a potential green technology for electrochemical treatment of azo dyes in wastewaters using Acid Red 1 as a model analyte. These films were synthesised by anodically polymerising pyrrole in the presence of Acid Red 1 as a supporting electrolyte. In this way, the anionic Acid Red 1 is electrostatically attracted to the cationic polypyrrole backbone formed to maintain electroneutrality, and is thus entrapped in the film. These Acid Red 1-entrapped polypyrrole films were characterised by electrochemical, microscopic and spectroscopic techniques. Based on a two-level factorial design, the solution pH, Acid Red 1 concentration and polymerisation duration were identified as significant parameters affecting the entrapment efficiency. The entrapment process will potentially aid in decolourising Acid Red 1-containing wastewaters. Similarly, in a cathodic process, electrons are supplied to neutralise the polypyrrole backbone, liberating Acid Red 1 into a solution. In this work, following an entrapment duration of 480 min in 2000 mg L(-1) Acid Red 1, we estimated 21% of the dye was liberated after a reduction period of 240 min. This allows the recovery of Acid Red 1 for recycling purposes. A distinctive advantage of this electrochemical Acid Red 1 treatment, compared to many other techniques, is that no known toxic by-products are generated in the treatment. Therefore, conducting polypyrrole films can potentially be applied as an environmentally friendly treatment method for textile effluents.

Minimizing fouling at hydrogenated conical-tip carbon electrodes during dopamine detection in vivo.

In this paper, physically small conical-tip carbon electrodes (∼2-5 µm diameter and ∼4 µm axial length) were hydrogenated to develop a probe capable of withstanding fouling during dopamine detection in vivo. Upon hydrogenation, the resultant hydrophobic sp(3) carbon surface deters adsorption of amphiphilic lipids, proteins, and peptides present in extracellular fluid and hence minimizes electrode fouling. These hydrogenated carbon electrodes showed a 35% decrease in sensitivity but little change in the limit of detection for dopamine over a 7-day incubation in a synthetic laboratory solution containing 1.0% (v/v) caproic acid (a lipid), 0.1% (w/v) bovine serum albumin and 0.01% (w/v) cytochrome C (both are proteins), and 0.002% (w/v) human fibrinopeptide B (a peptide). Subsequently, during dopamine detection in vivo, over 70% of the dopamine oxidation current remained after the first 30 min of a 60-min experiment, and at least 50% remained over the next half-period at the hydrogenated carbon electrodes. On the basis of these results, an initial average electrode surface fouling rate of 1.2% min(-1) was estimated, which gradually declined to 0.7% min(-1). These results support minimal fouling at hydrogenated carbon electrodes applied to dopamine detection in vivo.

Parotid metastatic disease from cutaneous squamous cell carcinoma: prognostic role of facial nerve sacrifice, lateral temporal bone resection, immune status and P-stage.

BACKGROUND: Recognized prognostic indicators for metastatic cutaneous squamous cell carcinoma (SCC) of the head and neck include facial nerve involvement, immune status, and "parotid" staging system (P-stage). We sought to examine the impact of lateral temporal bone resection (LTBR) on prognosis. METHODS: We conducted a retrospective analysis of 160 patients with metastatic cutaneous SCC to the parotid. All patients had parotidectomy and neck dissection; 27% had additional LTBR when the tumor was adherent to the temporal bone. RESULTS: Overall 5-year survival was 48%, disease-specific survival 77%, and locoregional control 83%. Corresponding results for immunocompetent versus immunocompromised were 55%, 86%, and 87% versus 12%, 48%, and 64%. On Cox regression analysis, only immunocompromised status (ie, lymphoproliferative disorder, organ-transplant patient) was prognostically significant (p < .001). CONCLUSION: More radical resection that may include LTBR mitigates the poorer prognosis with advanced disease in our series. Treatment must be individualized in immunocompromised patients who have shortened overall survival.

Anterior ethmoidal artery emerging anterior to bulla ethmoidalis: An abnormal anatomical variation in Waardenburg's syndrome.

In endoscopic sinus surgery, the anterior ethmoidal artery (AEA) is usually identified as it traverses obliquely across the fovea ethmoidalis, posterior to the bulla ethmoidalis and anterior to or within the ground lamella's attachment to the skull base. Injury to the AEA may result in hemorrhage, retraction of the AEA into the orbit, and a retrobulbar hematoma. The resulting increase in intraorbital pressure may threaten vision. Waardenburg's syndrome (WS) is a rare congenital, autosomal dominantly inherited disorder, distinguished by characteristic facial features, pigmentation abnormalities, and profound, congenital, sensorineural hearing loss. We present a case of AEAs located anterior to the bulla ethmoidalis in a 36-year-old male with WS and chronic rhinosinusitis. The anatomic abnormality was not obvious on a preoperative computed tomography scan and was discovered intraoperatively when the left AEA was injured, resulting in a retrobulbar hematoma. The hematoma was immediately identified and decompressed endoscopically without lasting complications. The AEA on the right was identified intraoperatively and preserved. The characteristic craniofacial features in WS were probably associated with the abnormal vascular anatomy. Endoscopic sinus surgeons should be aware of these potential anatomic anomalies in patients with abnormal craniofacial development.