The influence of facemasks on communication in healthcare settings: a systematic review.

PURPOSE: Although a well-established aspect of healthcare practice, the impact of facemasks on verbal communication is surprisingly ambiguous. MATERIALS AND METHODS: A systematic search was conducted in APA PSYCHinfo, CINAHL, NHS Knowledge Network, Medline and SPORTDiscus databases from inception to November 2022 according to the PRISMA guidelines. Studies reporting an objective measure of speech understanding in adults, where information was transmitted or received whilst wearing a facemask were included. Risk of bias of included studies was assessed with the Newcastle-Ottawa score. RESULTS: Four hundred and thirty-three studies were identified, of which fifteen were suitable for inclusion, incorporating 350 participants with a median age of 49 (range 19 to 74) years. Wide heterogeneity of test parameters and outcome measurement prohibited pooling of data. 93% (14 of 15) studies reported a deleterious effect of facemasks on speech understanding, and 100% (5 of 5) of the included studies reported attenuation of sound with facemask usage. Background noise added further deleterious effects on speech understanding which was particularly problematic within hearing-impaired populations. Risk of bias in included studies varied but overall was modest. CONCLUSIONS: Despite considerable complexity and heterogeneity in outcome measure, 93% (14 of 15) articles suggest respiratory protective equipment negatively affects speech understanding in normal hearing and hearing-impaired adults.

As a result of the covid-19 pandemic, facemask use is now commonplace across all healthcare and rehabilitation settings and has material implications for interpersonal communication.This systematic review of human communicative studies highlights that the use of facemasks does indeed inhibit communication through effects on speech intelligibility and through sound attenuation.These effects are evident in both normal hearing and hearing-impaired adults due to the visual cues required with lipreading and facial expressions during communication.The presence of background noise also produces deleterious effects on speech understanding and is more problematic for hearing-impaired populations.Simple recommendations to reduce background noise (where possible), to step closer (where social-distancing rules permit), to speak louder or to use speech to text applications (if practical) could all mitigate these communicative barriers. Further an awareness of persons with hearing impairments, the function (or otherwise) of hearing aids in those patients that require these, and an ability to use transparent facemasks can be specifically helpful.

Exploring clinical management of cognitive and behavioural deficits in MND. A scoping review.

OBJECTIVES: Little is known about how cognitive and behavioural decline in MND is managed clinically. This review aimed to summarise clinical management approaches of cognitive and behavioural decline in MND reported in peer-reviewed and grey literature. METHODS: A scoping review was conducted across Embase, Medline, Psychinfo and Emcare in October 2022. Grey literature was also searched across Google Scholar and Google in October 2022. RESULTS: A total of N = 26 studies and 8 documents were included. Thematic analysis revealed six key areas of clinical management: i. Assessment, ii. Education, iii. Advance Care Planning, iv. Adaptation of Care Plan, v. Communication and vi. Carer Support. CONCLUSIONS: The literature on management of cognitive and behavioural decline in MND is sparse. Most peer-reviewed literature consists of expert commentary and there is a lack of primary data to guide practitioners and families on how to manage cognitive and behavioural change in MND. PRACTICE IMPLICATIONS: Determining as early as practicable the presence of cognitive and behavioural changes in pwMND will enable practitioners to make adaptations to communication, provide education and supported decision-making for forward planning. This will enable individualised care, planned in partnership with families with MND, which incorporates personal needs and wishes.

Behavioral Interventions Targeting Base of Tongue to Posterior Pharyngeal Wall Approximation: A Scoping Review.

Pharyngeal pressure generated by approximation of the base of tongue to the posterior pharyngeal wall (BOT-PPW approximation) is critical for efficient pharyngeal bolus passage and is a frequent goal of dysphagia management. This scoping review evaluated behavioral interventions available to improve BOT-PPW approximation. We searched MEDLINE, CINAHL, Ovid Emcare, Web of Science, SCOPUS, and ProQuest for studies that met the following criteria: (i) behavioral interventions targeting BOT-PPW approximation, which (ii) were assessed using BOT-PPW-specific outcome measures, and (iiia) performed over a period of time (Review Part 1) or (iiib) studied immediate effects (Review Part 2). Study quality was rated using the GRADE framework. Data were extracted and synthesized into dominant themes. Of the 150 studies originally identified, three examined long-term effects (two single cases studies of individuals with dysphagia, and a third study evaluating effortful swallowing in healthy individuals). BOT-PPW approximation only increased in the two single case studies. Twenty-one studies evaluating immediate effects were categorized as follows: (1) effortful swallowing, (2) Mendelsohn maneuver, (3) tongue-hold maneuver, (4) super supraglottic swallowing maneuver, and (5) non-swallowing exercises. Across all studies, varying levels of success in increasing BOT-PPW approximation were reported. Four of 21 immediate effects studies evaluated patients with demonstrated swallowing impairment, whereas 17 studies evaluated healthy adults. Quality assessment revealed low strength of the existing evidence base. The evidence base for rehabilitative interventions targeting BOT-PPW approximation is severely limited and translation is hindered by small sample sizes and methodological limitations. Further clinical research is warranted.

Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy.

Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1-4. Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-195. Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19. Using several animal disease models of COVID-196,7, we demonstrate that selective engagement of activating Fcγ receptors results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection against SARS-CoV-2 challenge and for treatment of pre-infected animals. Our results highlight the importance of Fcγ receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fcγ receptor engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function and improved clinical efficacy against COVID-19 disease.

One-Pot Conversion of Free Sialoglycans to Functionalized Glycan Oxazolines and Efficient Synthesis of Homogeneous Antibody-Drug Conjugates through Site-Specific Chemoenzymatic Glycan Remodeling.

Antibody-drug conjugates (ADCs) are an important class of therapeutic agents that harness the highly specific antigen targeting property of antibodies to deliver toxic drugs for targeted cell killing. Site-specific conjugation methods are highly desirable for constructing homogeneous ADCs that possess a well-defined antibody-to-drug ratio, stability, ideal pharmacological profile, and optimal therapeutic index. We report here a facile synthesis of functionalized glycan oxazolines from free sialoglycans that are key donor substrates for enzymatic Fc glycan remodeling and the application of an efficient endoglycosidase mutant (Endo-S2 D184M) for site-specific glycan transfer to construct homogeneous ADCs. We found that by a sequential use of two coupling reagents under optimized conditions, free sialoglycans could be efficiently converted to selectively functionalized glycan oxazolines carrying azide-, cyclopropene-, and norbornene-tags, respectively, in excellent yield and in a simple one-pot manner. We further demonstrated that the recently reported Endo-S2 D184 M mutant was highly efficient for Fc glycan remodeling with the selectively modified glycan oxazolines to introduce tags into an antibody, which required a significantly smaller amount of glycan oxazolines and a much shorter reaction time than that of the Endo-S D233Q-catalyzed reaction, thus minimizing the side reactions. Finally homogeneous ADCs were constructed with three different click reactions. The resulting ADCs showed excellent serum stability, and in vitro cytotoxicity assays indicated that all the three ADCs generated from the distinct click reactions possessed potent and comparable cytotoxicity for targeted cancer cell killing.

Fc-engineered antibody therapeutics with improved efficacy against COVID-19.

Monoclonal antibodies (mAbs) with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefit in cases of mild to moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1-4. Treatment generally requires the administration of high doses of these mAbs with limited efficacy in preventing disease complications or mortality among hospitalized COVID-19 patients5. Here we report the development and evaluation of Fc-optimized anti-SARS-CoV-2 mAbs with superior potency to prevent or treat COVID-19 disease. In several animal models of COVID-19 disease6,7, we demonstrate that selective engagement of activating FcγRs results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection upon SARS-CoV-2 challenge and treatment of pre-infected animals. Our results highlight the importance of FcγR pathways in driving antibody-mediated antiviral immunity, while excluding any pathogenic or disease-enhancing effects of FcγR engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered mAbs with optimal Fc effector function and improved clinical efficacy against COVID-19 disease.

The impact of cognitive decline in amyotrophic lateral sclerosis on swallowing. A scoping review.

Purpose: Impaired swallowing is a serious symptom of amyotrophic lateral sclerosis (ALS) impacting on health and wellbeing. Little is known about how cognitive impairment in amyotrophic lateral sclerosis impacts on oropharyngeal swallowing. A scoping review was undertaken to explore how cognitive impairment impacts on a person living with ALS's (plwALS) ability to understand and manage oropharyngeal swallowing function.Method: Subject headings and keywords were searched across MEDLINE, SCOPUS, CINAHL, PsychINFO, Emcare and Google Scholar in May 2019. Articles containing information on amyotrophic lateral sclerosis and cognition and swallowing were reviewed. A secondary search was conducted in July 2020 with broadened search terms.Result: The primary search identified 1055 articles, and 47 were included for full-text review. Of these, no articles directly met the inclusion criteria of both cognitive impairment and swallowing. The secondary search with broadened terms identified an additional 762 studies, and 9 were included for full-text review, but none met the inclusion criteria. Consequently, thematic analysis was completed on articles from the full-text review to identify themes that related to both cognition and swallowing. The themes identified were: (i) early specialised multidisciplinary management of ALS achieves better outcomes; (ii) cognitive impairment impacts on management; and (iii) impaired swallowing occurs in nearly all people living with ALS and is a serious symptom of the disease.Conclusion: The interaction between cognitive impairment and oropharyngeal swallowing function in ALS has not been investigated. This is important, as cognitive impairment impacts insight and decision-making and may have implications for oropharyngeal swallowing management.

Glycolytic inhibitor 2-deoxyglucose suppresses inflammatory response in innate immune cells and experimental staphylococcal endophthalmitis.

Previously, we have shown that Staphylococcus (S) aureus induces a glycolytic response in retinal residential (microglia) and infiltrated cells (neutrophils and macrophages) during endophthalmitis. In this study, we sought to investigate the physiological role of glycolysis in bacterial endophthalmitis using a glycolytic inhibitor, 2-deoxyglucose (2DG). Our data showed that 2DG treatment attenuated the inflammatory responses of mouse bone marrow-derived macrophages (BMDM) and neutrophils (BMDN) when challenged with either live or heat-killed S. aureus (HKSA). Among the inflammatory mediators, 2DG caused a significant reduction in levels of cytokines (TNF-α, IL-1ß, IL-6) and chemokines (CXCL1 and CXCL2). Western blot analysis of 2DG treated cells showed downregulation of bacterial-induced MEK/ERK pathways. In vivo, intravitreal administration of 2DG both pre- and post-bacterial infection resulted in a significant reduction in intraocular inflammation in C57BL/6 mouse eyes and downregulation of ERK phosphorylation in retinal tissue. Collectively, our study demonstrates that 2DG attenuates inflammatory response in bacterial endophthalmitis and cultured innate immune cells via inhibition of ERK signaling. Thus glycolytic inhibitors in combination with antibiotics could mitigate inflammation-mediated tissue damage in ocular infections.

Glycyrrhizin Use for Multi-Drug Resistant Pseudomonas aeruginosa: In Vitro and In Vivo Studies.

Purpose: Our purpose was to test glycyrrhizin (GLY) effects and ciprofloxacin interactions on multidrug resistant (MDR) isolates of Pseudomonas aeruginosa in vitro and in vivo in a mouse model of keratitis. Methods: A Hardy-disk tested antibiotic sensitivity of isolates MDR9 (nonocular) and B1045 (ocular). GLY MIC (both isolates) and ciprofloxacin was determined spectrophotometrically. A live/dead assay using confocal microscopy and plate count, tested GLY effects on bacterial permeabilization/viability. Proteomics profiled bacterial efflux pumps (MDR9 vs. PAO1); RT-PCR comparatively tested GLY effects on their mRNA expression levels. The activity of efflux pumps was tested using ethidium bromide (EB); and scanning electron microscopy (SEM) visualized the effects of GLY treatment of bacteria. A combination of GLY and ciprofloxacin was tested in C57BL/6 mice (begun 18 hours after infection) and disease scored, photographed and MPO and plate counts done. Results: MDR9 was resistant to 6/12 and B1045 to 7/12 antibiotics (both to ciprofloxacin). MIC GLY for MDR9 was 40 mg/mL and 15 mg/mL for B1045. Ciprofloxacin MIC (32 µg/mL) was reduced 2-fold to 16 µg/mL when ciprofloxacin and GLY were combined. GLY altered bacterial membrane permeability and reduced viability. Proteomics revealed increased efflux pumps in MDR9 versus PAO1; GLY reduced their mRNA expression levels and EB suggested decreased activity. In C57BL/6 mice, treatment with GLY and ciprofloxacin versus ciprofloxacin, significantly reduced clinical scores, plate count, and MPO. Conclusions: GLY decreases MDR by: altering bacterial parameters, including viability and efflux pump activity. In vivo, it increases the effectiveness of ciprofloxacin, reducing ocular disease, plate count, and MPO activity.

The miR-183/96/182 Cluster Regulates Macrophage Functions in Response to Pseudomonas aeruginosa.

Macrophages (Mϕ) are an important component of the innate immune system; they play critical roles in the first line of defense to pathogen invasion and modulate adaptive immunity. MicroRNAs (miRNAs) are a newly recognized, important level of gene expression regulation. However, their roles in the regulation of Mϕ and the immune system are still not fully understood. In this report, we provide evidence that the conserved miR-183/96/182 cluster (miR-183/96/182) modulates Mϕ function in their production of reactive nitrogen (RNS) and oxygen species (ROS) and their inflammatory response to Pseudomonas aeruginosa (PA) infection and/or lipopolysaccharide (LPS) treatment. We show that knockdown of miR-183/96/182 results in decreased production of multiple proinflammatory cytokines in response to PA or LPS treatment in Mϕ-like Raw264.7 cells. Consistently, peritoneal Mϕ from miR-183/96/182-knockout versus wild-type mice are less responsive to PA or LPS, although their basal levels of proinflammatory cytokines are increased. In addition, overexpression of miR-183/96/182 results in decreased production of nitrite and ROS in Raw264.7 cells. We also provide evidence that DAP12 and Nox2 are downstream target genes of miR-183/96/182. These data suggest that miR-183/96/182 imposes global regulation on various aspects of Mϕ function through different downstream target genes.

HMGB1 Antagonist, Box A, Reduces TLR4, RAGE, and Inflammatory Cytokines in the Cornea of P. aeruginosa-Infected Mice.

PURPOSE: High mobility group box 1 (HMGB1) contributes to adverse disease outcome in Pseudomonas aeruginosa keratitis. This study tests Box A, an HMGB1 antagonist, in a model of the disease. METHODS: C57BL/6 mice (B6) were injected subconjunctivally (1 day before infection) with Box A or phosphate-buffered saline (PBS), infected with P. aeruginosa strain ATCC 19660, and injected intraperitoneally with Box A or PBS at 1 and 3 days postinfection (p.i.). Clinical scores, photographs with a slit lamp camera, real-time polymerase chain reaction (RT-PCR), western blot, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), myeloperoxidase (MPO), and bacterial plate count were used to assess disease outcome. In separate experiments, the therapeutic potential of Box A was tested as described above, but with treatment begun at 6 h p.i. RESULTS: Box A versus PBS prophylactic treatment significantly reduced clinical scores, MPO activity, bacterial load, and expression of TLR4, RAGE, IL-1ß, CXCL2, and TNF-α in the infected cornea. Box A blocked co-localization of HMGB1/TLR4 in infiltrated cells in the stroma at 3 and 5 days p.i., but only at 5 days p.i. for HMGB1/RAGE. Box A versus PBS therapeutic treatment significantly reduced clinical scores, MPO activity, bacterial load, and protein levels of IL-1ß, CXCL2, and IL-6 in the infected cornea. CONCLUSION: Overall, Box A lessens the severity of Pseudomonas keratitis in mice by decreasing expression of TLR4, RAGE (their interaction with HMGB1), IL-1ß, CXCL2 (decreasing neutrophil infiltrate), and bacterial plate count when given prophylactically. Therapeutic treatment was not as effective at reducing opacity (disease), but shared similar features with pretreatment of the mice.

Six-Minute Walk Test Distances in Fast-Track and Traditional Cardiac Rehabilitation: A 3-YEAR DATABASE REVIEW.

PURPOSE: Home-based and center-based cardiac rehabilitation (CR) have demonstrated similar levels of risk factor reduction. Cardiac rehabilitation models with fewer exercise sessions may be as effective as traditional models. This study reviewed a community phase II CR database from 2007 to 2010. METHODS: A fast-track CR (FTCR) group was introduced alongside an existing traditional CR (TCR) program. The 2 programs ran concurrently on different days. Both FTCR and TCR treatment groups undertook supervised low to moderate intensity exercise training for 6 weeks and were provided with home exercise advice. Fast-track CR included once-weekly exercise sessions and a 1-time 7-hour education session; TCR included twice-weekly exercise and education sessions. Similar education was provided in both programs. Six-minute walk test distance (6MWD) was assessed pre-CR and post-CR for both groups. RESULTS: Six hundred and twenty patients enrolled in CR during the period, and patients elected or were assigned (not randomized) to FTCR (n = 197) or to TCR (n = 423) treatment groups. Complete 6MWD data sets were available for 115 FTCR and 254 TCR subjects. Repeated-measures analysis of variance found 6MWD outcomes to be similar for both groups over both assessments combined and at each assessment point. Improvements in 6MWD post-CR were different for men and women in the CR database (8% vs 5%, respectively, P < .001). CONCLUSIONS: Six-minute walk test distance outcomes were not different for subjects undergoing once-weekly or twice-weekly supervised CR exercise sessions. CR models with fewer supervised exercise sessions may provide similar functional outcomes to traditional CR models.

Timed Up and Go Tests in cardiac rehabilitation: reliability and comparison with the 6-Minute Walk Test.

PURPOSE: To test the reliability of Timed Up and Go Tests (TUGTs) in cardiac rehabilitation (CR) and compare TUGTs to the 6-Minute Walk Test (6MWT) for outcome measurement. METHODS: Sixty-one of 154 consecutive community-based CR patients were prospectively recruited. Subjects undertook repeated TUGTs and 6MWTs at the start of CR (start-CR), postdischarge from CR (post-CR), and 6 months postdischarge from CR (6 months post-CR). The main outcome measurements were TUGT time (TUGTT) and 6MWT distance (6MWD). RESULTS: Mean (SD) TUGTT1 and TUGTT2 at the 3 assessments were 6.29 (1.30) and 5.94 (1.20); 5.81 (1.22) and 5.53 (1.09); and 5.39 (1.60) and 5.01 (1.28) seconds, respectively. A reduction in TUGTT occurred between each outcome point (P ≤ .002). Repeated TUGTTs were strongly correlated at each assessment, intraclass correlation (95% CI) = 0.85 (0.76-0.91), 0.84 (0.73-0.91), and 0.90 (0.83-0.94), despite a reduction between TUGTT1 and TUGTT2 of 5%, 5%, and 7%, respectively (P ≤ .006). Relative decreases in TUGTT1 (TUGTT2) occurred from start-CR to post-CR and from start-CR to 6 months post-CR of -7.5% (-6.9%) and -14.2% (-15.5%), respectively, while relative increases in 6MWD1 (6MWD2) occurred, 5.1% (7.2%) and 8.4% (10.2%), respectively (P < .001 in all cases). Pearson correlation coefficients for 6MWD1 to TUGTT1 and TUGTT2 across all times were -0.60 and -0.68 (P < .001) and the intraclass correlations (95% CI) for the speeds derived from averaged 6MWDs and TUGTTs were 0.65 (0.54, 0.73) (P < .001). CONCLUSIONS: Similar relative changes occurred for the TUGT and the 6MWT in CR. A significant correlation between the TUGTT and 6MWD was demonstrated, and we suggest that the TUGT may provide a related or a supplementary measurement of functional capacity in CR.

Repeated six-minute walk tests for outcome measurement and exercise prescription in outpatient cardiac rehabilitation: a longitudinal study.

OBJECTIVE: To determine whether repeated 6-minute walk tests (6MWTs) are required for outcome measurement and exercise prescription in a typical cardiac rehabilitation (CR) population. DESIGN: Prospective longitudinal observational study. SETTING: Outpatient community health center. PARTICIPANTS: Sixty-one of 154 consecutive patients. INTERVENTION: 6MWTs (N = 2) were conducted at 3 assessment points: at CR start, postcompletion, and 6-months postcompletion. MAIN OUTCOME MEASURE: 6MWT distance (6MWD). RESULTS: Mean 6MWD for the first (6MWT1) and second (6MWT2) 6MWTs at the 3 assessment points were 507 ± 85 (522 ± 84), 532 ± 86 (560 ± 87), and 549 ± 99 (575 ± 107)m. Repeated 6MWDs strongly correlated at each assessment point, with intraclass correlation coefficients of .96 (95% confidence interval [CI], 0.93-.98), .97 (95% CI, .92-.98), and .94 (95% CI, .89-.97), respectively. Relative increases in mean 6MWD from 6MWT1 to 6MWT2 at each assessment point were 3%, 5%, and 5%, respectively (P<.001 in each case). Differences in walking speed derived from 6MWD1 and 6MWD2 did not translate into differences in exercise prescription. CONCLUSIONS: The difference between 6MWD1 and 6MWD2 was consistent regardless of previous exposure to 6MWTs. A single 6MWT was as effective as 2 repeated 6MWTs for outcome measurement and exercise prescription. We therefore recommend that when 6MWDs are used for CR outcome measurement, either a single 6MWT be used or the number of 6MWTs performed be consistent at all assessment points.

A mobile phone-based care model for outpatient cardiac rehabilitation: the care assessment platform (CAP).

BACKGROUND: Cardiac rehabilitation programs offer effective means to prevent recurrence of a cardiac event, but poor uptake of current programs have been reported globally. Home based models are considered as a feasible alternative to avoid various barriers related to care centre based programs. This paper sets out the study design for a clinical trial seeking to test the hypothesis that these programs can be better and more efficiently supported with novel Information and Communication Technologies (ICT). METHODS/DESIGN: We have integrated mobile phones and web services into a comprehensive home- based care model for outpatient cardiac rehabilitation. Mobile phones with a built-in accelerometer sensor are used to measure physical exercise and WellnessDiary software is used to collect information on patients' physiological risk factors and other health information. Video and teleconferencing are used for mentoring sessions aiming at behavioural modifications through goal setting. The mentors use web-portal to facilitate personal goal setting and to assess the progress of each patient in the program. Educational multimedia content are stored or transferred via messaging systems to the patients phone to be viewed on demand. We have designed a randomised controlled trial to compare the health outcomes and cost efficiency of the proposed model with a traditional community based rehabilitation program. The main outcome measure is adherence to physical exercise guidelines. DISCUSSION: The study will provide evidence on using mobile phones and web services for mentoring and self management in a home-based care model targeting sustainable behavioural modifications in cardiac rehabilitation patients. TRIAL REGISTRATION: The trial has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) with number ACTRN12609000251224.

Detection of rare disseminated tumor cells identifies head and neck cancer patients at risk of treatment failure.

PURPOSE: This study was designed to help establish the most appropriate samples and tests to detect disseminated tumor cells (DTCs) for head and neck cancer patients. EXPERIMENTAL DESIGN: Samples of bone marrow (BM) and central venous blood (CVB), collected preoperatively, and BM and peripheral venous blood, collected 3 months transcription postoperatively, were screened for the presence of DTCs using immunocytochemistry (ICC) with a pan-cytokeratin antibody and E48 reverse transcriptase-PCR. The molecular approach was also applied to intraoperative CVB. RESULTS: The concordance between the molecular and ICC tests applied to preoperative samples, measured by Cohen's kappa, was not uniformly good, which likely reflected sampling errors, heterogeneity of E48 antigen expression, or stochastic effects. However, testing samples of BM and CVB preoperatively with the molecular or ICC approaches gave results that predicted disease-free survival and distant-metastases-free survival. Application of a single preoperative test predicted development of distant metastases, and the prediction could be improved by combining information derived from testing both CVB and BM. Applying two tests to the same sample of blood or BM served to validate the findings from a single assay but did not improve the prediction. Testing the intraoperative sample of CVB was also a sensitive predictor of distant metastases, but testing BM or blood 3 months postsurgery was not useful. CONCLUSIONS: These findings suggest that detection of DTCs pre- or intraoperatively indicates a high risk of local and distant recurrence and reduced survival in head and neck cancer.