Sensorineural Hearing Loss in Nasopharyngeal Carcinoma Survivors in the Modern Treatment Era - The Early and Late Effects of Radiation and Cisplatin.

AIMS: Hearing loss is a common debilitating complication in nasopharyngeal carcinoma (NPC) survivors. The aim of the present study was to investigate the impact of inner ear/cochlear radiation dose and cisplatin use on early and late sensorineural hearing loss (SNHL) in NPC patients treated with radiotherapy alone, concurrent chemoradiation (cCRT) and induction chemotherapy followed by cCRT (iCRT) in the intensity-modulated radiotherapy era. MATERIALS AND METHODS: The study included 81 NPC patients treated with intensity-modulated radiotherapy between 2014 and 2016. Pure tone audiometry was carried out at baseline and follow-up. The effects of cochlear/inner ear radiation and cisplatin doses on early (<12 months) and late (≥24 months) SNHL were analysed using multivariable regression after adjusting for important predictors. RESULTS: In total, 156 ears were examined. In early SNHL (n = 136), cisplatin use predicted the incidence of early high-frequency SHNL (HF-SNHL) (odds ratio 6.4, 95% confidence interval 1.7-23.9, P = 0.005). Ninety ears were analysed for late SNHL (median follow-up 38 months). Inner ear/cochlear radiation and cisplatin doses and better pre-treatment hearing were independent predictors of threshold change at 4 kHz. Every 10 Gy increase in inner ear/cochlear Dmean resulted in 5-dB and 6-dB threshold changes, respectively (cochlear Dmean: B = 0.005, 95% confidence interval 0.0004-0.009, P = 0.031; inner ear Dmean: B = 0.006, 95% confidence interval 0.001-0.010, P = 0.014). Cisplatin use was associated with late HF-SNHL (odds ratio 3.74, 95% confidence interval 1.1-12.3, P = 0.031). In the cCRT and iCRT subgroups, no cisplatin dose-dependent ototoxicity was observed. Severe (≥30 dB) late HF-SNHL occurred in 14% and 25% of the patients when the cochlear dose constraints were 40 Gy and 44 Gy, respectively. The radiotherapy-alone group did not develop severe late HF-SNHL. CONCLUSION: Cochlear/inner ear radiation dose and cisplatin use showed differential and independent ototoxicity in early and late SNHL. As cochlear/inner ear dose-dependent ototoxicity was demonstrated, the cochlear dose constraint should be as low as reasonably achievable, especially when cisplatin is also administered.

Comparing respiratory polygraphy with pulse transit time analysis versus overnight polysomnography in the diagnosis of obstructive sleep apnoea in children.

OBJECTIVE: Obstructive sleep apnea syndrome in children is associated with significant morbidity. Polysomnography is the main diagnostic tool but is time consuming and requires skilled manpower to supervise the patient overnight and hence long referral to diagnosis time. However, there are limitations and underestimation of the apnoea hyponea index (AHI) with alternative home sleep apnoea testing (HSAT), such as type 3 respiratory polygraphy (RP). Prior studies have demonstrated pulse transit time (PTT) to be a reliable indicator of cortical arousals. In this study, the use of PTT together with RP will be studied to determine whether the derived AHI is comparable to that of PSG. METHOD: Forty-five patients with suspected OSA met the inclusion criteria underwent PSG in the sleep laboratory for analysis. The raw data for either PSG or RP analysis were allocated separately to two different accredited sleep technicians. The primary outcome AHI derived from PTT with RP was compared to the AHI derived from PSG. Secondary outcomes compared were obstructive apnoea index (OAI), total hypopnoea index (THI) and arousal index (AI). Bland Altman analysis was used to compare the agreement of AHI derived from the 2 modalities and demonstrate whether RP is non inferior or equivalent to the gold standard for diagnosing OSAS. RESULTS: The patients studied had a median age of 8.8 years (range 3-17 years). The patients were not limited to certain spectrum of severity OSA and had AHI results spread from mild to severe OSA (AHI 0.4/hr to 72.2/hr). The RP with PTT-derived AHI was strongly correlated to the PSG derived AHI as seen on the Spearman plot (r = 0.98). The Bland Altman plot showed no evidence of underestimation of the AHI due to missed arousal related hypopneas. The difference of AHI derived from RP and PSG results were clinically insignificant. The differences between the PSG and RP total hypopnoea index (THI) and arousal index (AI) were also statistically insignificant. CONCLUSION: The study shows that RP with PTT can be considered a reliable diagnostic alternative compared with PSG. The role of PTT incorporated with RP was to minimize underestimation of AHI due to missed arousal associated hypopnea events. The results were apparent across mild to severe severity of OSA. There are advantages of RPs particularly in paediatrics. Overall this study offers promising preliminary insights that RP incorporated with PTT can be further explored as an acceptable home diagnostic tool for diagnosing OSA in children.

There is no routine head and neck exam during the COVID-19 pandemic.

Head and neck examinations are commonly performed by all physicians. In the era of the COVID-19 pandemic caused by the SARS-CoV-2 virus, which has a high viral load in the upper airways, these examinations and procedures of the upper aerodigestive tract must be approached with caution. Based on experience and evidence from SARS-CoV-1 and early experience with SARS-CoV-2, we provide our perspective and guidance on mitigating transmission risk during head and neck examination, upper airway endoscopy, and head and neck mucosal surgery including tracheostomy.

Effects of Salivary Mg on Head and Neck Carcinoma via TRPM7.

Magnesium (Mg) has been known to play vital roles in regulating growth and various metabolic processes. In recent years, the association between Mg and tumorigenesis has raised more and more attention. However, the effects of Mg on the progression of head and neck carcinoma (HNC), as well as the mechanism behind it, remain undefined. In this study, the roles of Mg in tumorigenic activities were tested in CAL27 and FaDu cells as well as in a xenograft tumor model in nude mice. We demonstrated that a moderate increase in extracellular Mg contributed to the proliferation, migration, and invasion of 2 HNC cell lines, while the addition of Mg in drinking water promoted the growth of xenograft tumors in mice without altering their serum Mg levels. Moreover, TRPM7, a major Mg transporter, was shown to be essential for the tumorigenic activities of HNC and the Mg-induced promotive effects on HNC cells and was further shown to be associated with the activation of AKT/mTOR (mammalian target of rapamycin) signaling. In a preliminary clinical study, we determined the Mg ion concentrations in the stimulated saliva from 72 patients with nasopharynx carcinoma and 12 healthy individuals. Our data revealed that the salivary Mg levels of subjects with nasopharynx carcinoma were significantly higher than those of the healthy controls. This is correlated with our finding showing TRPM7 to be overexpressed in tumor tissues harvested from 9 patients with HNC. Therefore, we can conclude that salivary Mg level, within a certain range, could act as a risk factor for the progression of HNC, which involves the activation of AKT/mTOR signaling pathways through the TRPM7 channel. The control of salivary Mg level and the intervention of TRPM7 should not be ignored during the study of HNC.

Moderate- to long-term therapeutic outcomes of treated aggressive periodontitis patients without regular supportive care.

BACKGROUND AND OBJECTIVE: Risk for deterioration in treated aggressive periodontitis (AgP) individuals remained unclear. This retrospective cohort study investigated 7-26 years of periodontal outcomes and oral health-related quality of life (OHRQoL) of young adults with advanced periodontitis. MATERIAL AND METHODS: Eighty-nine previously treated patients with AgP were re-examined. Clinical and radiographic parameters before treatment discontinuation and at re-examination were compared. OHRQoL at re-call was assessed with the short-form Oral Health Impact Profile (OHIP-14S). RESULTS: None of the subjects adhered to suggested periodontal therapy and maintenance after discharge. Mean percentage of sites with probing pocket depth (PPD) ≥6 mm at re-examination was 4.5 ± 5.9%. A total of 182 teeth had been lost over time. Tooth loss rate was 0.14/patient/year. From 68 subjects with documented favorable treatment outcomes, higher percentage of sites with PPD ≥6 mm at re-examination and higher radiographic proximal bone loss was associated with current smoking status. Patients with AgP with <20 teeth at re-call had worse OHRQoL than those with ≥20 teeth. Patients with higher full-mouth mean PPD also reported poorer OHRQoL. CONCLUSION: Treatment in patients with AgP who smoke and neglect proper supportive care, risk periodontal disease progression. Substantial tooth loss and higher full-mouth mean PPD led to poorer OHRQoL in this cohort.

Construction of poly(lactic-co-glycolic acid)/ZnO nanorods/Ag nanoparticles hybrid coating on Ti implants for enhanced antibacterial activity and biocompatibility.

Poly(lactic-co-glycolic acid)/Ag/ZnO nanorods coating were successfully prepared on the surface of Ti metallic implants using a hydrothermal method and subsequent spin-coating of mixtures of poly(lactic-co-glycolic acid) and silver nanoparticles. The poly(lactic-co-glycolic acid)/Ag/ZnO nanorods coating exhibited excellent antibacterial efficacy of over 96% against both Staphylococcus aureus and Escherichia coli when the initial content of Ag nanoparticles was over 3wt%. In addition, the release of both silver and zinc could last for over a hundred days due to the enwrapping of poly(lactic-co-glycolic acid). Proliferation of mouse calvarial cells exhibited minimal cytotoxicity on the poly(lactic-co-glycolic acid)/Ag/ZnO coating with an initial content of Ag nanoparticles of 1wt% and 3wt%, while it inhibited cell proliferation once this value was increased to 6wt%. The results revealed that this poly(lactic-co-glycolic acid)/Ag/ZnO composite could provide a long-lasting antibacterial approach and good cytocompatibility, thus exhibiting considerable potential for biomedical application in orthopedic and dental implants with excellent self-antibacterial activity and good biocompatibility.

Clinical use of venoarterial extracorporeal membrane oxygenation.

With advances in mechanical circulation, venoarterial extracorporeal membrane oxygenation has become an established technique to provide cardiopulmonary support for patients with cardiovascular collapse. This article reviews the physiological principles of such extracorporeal technique and its interaction with the native heart. Practical aspects including equipment, patient selection, and common complications with their prevention and specific management are summarised. The strategy for weaning from venoarterial extracorporeal membrane oxygenation is also discussed.

The controlled drug release by pH-sensitive molecularly imprinted nanospheres for enhanced antibacterial activity.

In this study, we prepared pH-sensitive hybrid nanospheres through the implementation of a facile molecularly imprinted polymer (MIP) technique combined with a UV-initiated precipitation polymerization method using vancomycin (VA) for the templates. During the course of this investigation, both 2-hydroxyethyl methacrylate (HEMA) and 2-(diethylamino) ethyl methacrylate (DEAEMA) were utilized as the functional monomers, while ethylene glycol dimethacrylate (EGDMA) was used as a cross-linker. The obtained MIP nanospheres exhibited well-controlled particle size, with a drug loading capacity of about 17%, much higher than that of the non-imprinted polymer (NIP) nanospheres (5%). In addition, the VA loading quantity was closely correlated with the dosage of the cross-linking agent, and the MIP nanospheres exhibited a slower and more controlled VA release rate than the NIP nanospheres. Moreover, these MIP nanospheres were sensitive to pH values, and consequently showed an increasing release rate of VA as the pH level was decreased. The VA-loaded MIP nanospheres showed the higher antibacterial ratio of over 92% against Staphylococcus aureus (S. aureus) while the NIP nanospheres were friendly to S. aureus. These MIP nanospheres can be promising for targeting drug delivery system to achieve specific therapies such as preventing bacterial infections and killing cancer cells without damaging health cells and tissues.

Construction of N-halamine labeled silica/zinc oxide hybrid nanoparticles for enhancing antibacterial ability of Ti implants.

The traditional antibiotic treatment for bacterial infections often induces antibiotic resistance in bacteria. In this work, we developed hybrid nanoparticles (NPs) with a self-antibacterial ability on Ti implants using monodispersed polystyrene-acrylic acid (PSA) nanoparticles as colloidal templates followed by the electrostatic adsorption of zinc oxide (ZnO) and the subsequent deposition of silica (SiO2) membrane on the outside. These synthesized PSA-ZnO-SiO2 NPs were pretreated by 5,5-dimethylhydantoin (DMH) before chlorination in a diluted NaClO solution. These nanoparticles (PSA-ZnO-SiO2-DMH) were subsequently labeled by N-halamines and then immobilized on the surface of titanium plates through hydrogen bonding. Field emission scanning electron microscopy (FE-SEM) and X-ray photoelectron spectroscopy (XPS) were utilized to characterize the modified surface. Antibacterial tests disclosed that the PSA-ZnO-SiO2-DMH-Cl NPs modified surface exhibited excellent antibacterial activity against both Pseudomonas aeruginosa (P.au), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro cell culture results revealed that PSA-ZnO-SiO2-DMH-Cl had no obvious cytotoxicity for an MC3T3-E1 preosteoblast. This novel surface system provides a promising self-antibacterial bioplatform for metallic implants without using antibiotics.

Clinical use of venovenous extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation has been used clinically for more than 40 years. The technique provides respiratory and/or circulatory support via venovenous and veno-arterial configurations, respectively. We review the basic physiological principles of extracorporeal membrane oxygenation systems in venovenous extracorporeal membrane oxygenation. Clinical aspects including patient selection, equipment, setup, and specific patient management are outlined. Pros and cons of the use of extracorporeal membrane oxygenation in respiratory failure are discussed.

Metal Ion Coordination Polymer-Capped pH-Triggered Drug Release System on Titania Nanotubes for Enhancing Self-antibacterial Capability of Ti Implants.

The current work reports a novel hybrid system with a highly efficient, bioresponsive, and controlled release of antibacterial activity via the metal ion coordination polymer on titania nanotubes (TNTs). These hybrid systems exhibited a self-defense behavior that is triggered by the change of the ambient environment acidity due to bacterial infection with Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). The antibacterial agents, including antibiotics and nanosilver particles, can be loaded into TNTs and then sealed with coordination polymers (CPs) through the attachment of metallic ions such as Zn2+ or Ag+. The zinc and silver ions work as intermediate coordination bonds, and they are sensitive to the change in H+. Because of the strong bonding of CPs, the amount of released antimicrobial agents is maintained at a nonsignificant level when pH is maintained at 7.4. However, the coordination bond of the capped CPs was triggered to open and release antibacterial agents from TNTs once the environment becomes acidic. The release rate gradually increased as the pH value further decreased. Subsequently, the antibacterial efficiency of the hybrid system is accelerated as the local microenvironment becomes more acidic during bacterial infection. In addition, the metal ions that are used for intermediate bond bridging are also favorable for specific biological functions. For example, Zn2+ can promote the proliferation of osteoblastic cells, while Ag+ can further enhance the antibacterial capability. In conclusion, this smart surface coating system not only demonstrates excellent self-antibacterial properties and biocompatibility but also formulates a controllable delivery system for the long-lasting treatment of biomaterial-related bacterial infections.

Construction of poly (vinyl alcohol)/poly (lactide-glycolide acid)/vancomycin nanoparticles on titanium for enhancing the surface self-antibacterial activity and cytocompatibility.

Comparing with traditional drug dosage form, controlled release systems offer more effective and favorable route to deliver drugs in optimum dose to specific sites with long term release duration. In this work, an effective drug delivery system composed of poly (vinyl alcohol) (PVA)/poly (lactide-glycolide acid) (PLGA) nanoparticles (NPs) with encapsulated vancomycin (Van), is constructed on the surface of biomedical titanium. The PVA/PLGA/Van NPs synthesized via double emulsion route are grafted onto the surface of titanium plates modified by alkaline-heat treatment and subsequent aminopropyltriethoxysilane (APTES) deposition. In vitro tests disclose that NPs can release a small amount of drugs continuously due to the slow swelling or hydrolysis of polymer chain segments as the immersion time increases. As the pH value reduces, the ester bonds rupture with releasing more drugs, which is why this drug delivery system exhibits the highest antibacterial efficiency at the lowest pH value of 4.5 in this work. Cell culture results reveal that this smart surface system on titanium facilitates the cell attachment and proliferation on implants. Hence, this pH controlled drug delivery system can be successfully applied as a bio-platform for improving both the osteoblasts adhesion and antibacterial activity of metallic implants.

Dopamine Modified Organic-Inorganic Hybrid Coating for Antimicrobial and Osteogenesis.

A hybrid coating composed of hydroxyapatite (HA), Ag nanoparticles (NPs), and chitosan (CS) was successfully prepared on a Ti substrate by a layer-by-layer assembly process. A polydopamine-assisted (PDA-assisted) coating showed a good bond with HA. Ag NPs were uniformly distributed into the hybrid coating through a solution method and ultraviolet light reduction. A CS nanofilm was deposited via spin-coating to control the release of Ag+ from the hybrid coating. The results disclosed that the 3-layer CS coating could efficiently control the release of Ag+ from the hybrid coating via the Fickian diffusion mechanism and that the PDA/HA/Ag/CS-1 coating exhibited antibacterial ratios of 63.0% and 51.8% against E. coli and S. aureus, respectively. Furthermore, the normal structure of E. coli was obviously destroyed by two types of Ag doped coatings. The cell viability assay showed that CS effectively reduced the cytotoxicity of the hybrid coating after a 7 day incubation. The hybrid coating presented high ALP activities at days 3 and 14. The results reveal that hybrid coatings can endow Ti implants with good antibacterial capability as well as cell viability and osteogenic activity.

Design of magnesium alloys with controllable degradation for biomedical implants: From bulk to surface.

The combination of high strength, light weight, and natural biodegradability renders magnesium (Mg)-based alloys promising in orthopedic implants and cardiovascular stents. Being metallic materials, Mg and Mg alloys made for scaffolds provide the necessary mechanical support for tissue healing and cell growth in the early stage, while natural degradation and reabsorption by surrounding tissues in the later stage make an unnecessarily follow-up removal surgery. However, uncontrolled degradation may collapse the scaffolds resulting in premature implant failure, and there has been much research in controlling the degradation rates of Mg alloys. This paper reviews recent progress in the design of novel Mg alloys, surface modification and corrosion mechanisms under different conditions, and describes the effects of the structure, composition, and surface conditions on the degradation behavior in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Owing to their unique mechanical properties, biodegradability, biocompatibility, Mg based biomaterials are becoming the most promising substitutes for tissue regeneration for impaired bone, vascular and other tissues because these scaffolds can provide not only ideal space for the growth and differentiation of seeded cells but also enough strength before the formation of normal tissues. The most important is that these scaffolds can be fully degraded after tissue regeneration, which can satisfy the increasing demand for better biomedical devices and functional tissue engineering biomaterials in the world. However, the rapid degradation rate of these scaffolds restricts the wide application in clinic. This paper reviews recent progress on how to control the degrdation rate based on the relevant corrosion mechanisms through the design of porous structure, phase structure, grains, and amorphous structure as well as surface modification, which will be beneficial to the better understanding and functional design of Mg-based scaffolds for wide clinical applications in tissue reconstruction in near futures.

Antibacterial Activity of Silver Doped Titanate Nanowires on Ti Implants.

A nanostructured film composed of one-dimensional titanate nanowires (TNWs) was employed as a carrier of Ag nanoparticles and chitosan (CS) to improve the surface antibacterial activity and biocompatibility of titanium implants. A TNWs film was produced on a Ti substrate by an alkali hydrothermal reaction and subsequently doped by Ag nanoparticles through an ultraviolet light chemical reduction. The CS nanofilm was deposited on the Ag nanoparticles through a spin-assisted layer by layer assembly method. The results disclosed that Ag nanoparticles were successfully carried by TNWs and homogeneously distributed on the entire surface. Moreover, a CS nanofilm was also successfully deposited on the Ag nanoparticles. Antibacterial tests showed that the samples modified with a higher initial concentration of AgNO3 solution exhibited better antibacterial activity, and that a CS nanofilm could further improve the antibacterial activity of the TNWs. Cell viability and ALP tests revealed that the release of Ag(+) was detrimental for the growth, proliferation, and differentiation of MC3T3, and that CS could lower the negative effects of Ag gradually as the incubation time increased.

The modulation of stem cell behaviors by functionalized nanoceramic coatings on Ti-based implants.

Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery. Stem cells have been found to have osteogenic capabilities. It is necessary to study the influences of functionalized nanoceramic coatings on the differentiation and proliferation of stem cells in vitro or in vivo. In this paper, we summarized the recent advance on the modulation of stem cells behaviors through controlling the properties of nanoceramic coatings, including surface chemistry, surface roughness and microporosity. In addition, mechanotransduction pathways have also been discussed to reveal the interaction mechanisms between the stem cells and ceramic coatings on Ti-based metals. In the final part, the osteoinduction and osteoconduction of ceramic coating have been also presented when it was used as carrier of BMPs in new bone formation.

Changes in the Attitude and Practice Toward End-of-Life Care: Perspective of Chinese Physicians in Medical Department.

INTRODUCTION: End-of-life care is affected by the attitude and cultural influence of doctors. METHODS: To investigate the attitudes and practices of doctors on end-of-life care by questionnaire survey in 2004 and 2008. RESULTS: In 2004, 31.7% of the respondents agreed that they "do not attempt resuscitation" (DNAR) form was useful and it rose to 54.4% in 2008. A higher proportion of respondents in 2008 claimed that they signed the DNAR form for documentation and accepted withholding noninvasive life-sustaining treatment compared to 2004. In 2004, 50% of the respondents regarded their training and education on handling DNAR issue as inadequate. CONCLUSION: Documentation by DNAR form is gaining wider acceptance. Many doctors are expected to have more training and coaching on communication for handling such sensitive issues.

Polymeric nanoarchitectures on Ti-based implants for antibacterial applications.

Because of the excellent mechanical properties and good biocompatibility, titanium-based metals are widely used in hard tissue repair, especially load-bearing orthopedic applications. However, bacterial infection and complication during and after surgery often causes failure of the metallic implants. To endow titanium-based implants with antibacterial properties, surface modification is one of the effective strategies. Possessing the unique organic structure composed of molecular and functional groups resembling those of natural organisms, functionalized polymeric nanoarchitectures enhance not only the antibacterial performance but also other biological functions that are difficult to accomplish on many conventional bioinert metallic implants. In this review, recent advance in functionalized polymeric nanoarchitectures and the associated antimicrobial mechanisms are reviewed.

Fluconazole resistance in Candida glabrata is associated with increased bud formation and metallothionein production.

Virulence associated with fluconazole (FL) resistance in Candida glabrata is a global problem and has not been well characterized at the proteome level. In this study, a stable FL-resistant (MIC >256 µg ml(-1)) strain of C. glabrata was generated on agar containing FL. Eight phenotypic mutants were characterized by contour-clamped homogeneous electrophoretic field analysis and two-dimensional PAGE. The secondary derivatives of C. glabrata yielded four distinct genotypes with varying chromosomal profiles. Proteomic analysis performed by tandem mass spectrometry for two of the mutants, CG(L2) and CG(S3), demonstrated a total of 25 differentially regulated proteins of which 13 were upregulated and 12 were downregulated or were similar compared with the parental isolate. The mRNA transcript levels of significantly (P<0.001) upregulated genes were determined by quantitative RT-PCR analysis, and their physiological relevance in terms of phenotypic expression of virulence attributes was verified by conventional laboratory methodologies. The data showed that the FL resistance (MIC >256 µg ml(-1)) of CG(S3) was associated with significantly upregulated (P<0.001) mRNA transcript levels of several genes - ERG11, CDR1, CDR2, MFS, MTI, TPR, VPS and EFT2 - in addition to a number of other potentially virulent genes expressed differentially at a lower level. The results demonstrated accentuated phenotypic expression of bud formation of yeast and metallothionein production associated with FL resistance in C. glabrata, which may help the fungus to colonize the host.