Effect of high-flow nasal oxygen on hypoxaemia during procedural sedation: a systematic review and meta-analysis.

We conducted a systematic review to evaluate the effect of high-flow nasal oxygen and conventional oxygen therapy during procedural sedation amongst adults and children. We searched MEDLINE, EMBASE and CINAHL for randomised controlled trials that reported the effects of high-flow nasal oxygen during procedural sedation. The primary outcome measure was hypoxaemia and the secondary outcomes were minimum oxygen saturation; hypercarbia; requirement for airway manoeuvres; and procedure interruptions. The quality of evidence was assessed using the revised Cochrane risk-of bias tool and grading of recommendations, assessment, development and evaluation (GRADE). Nineteen randomised controlled trials (4121 patients) including three in children were included. Administration of high-flow nasal oxygen reduced hypoxaemia, risk ratio (95%CI) 0.37 (0.24-0.56), p < 0.001; minor airway manoeuvre requirements, risk ratio (95%CI) 0.26 (0.11-0.59), p < 0.001; procedural interruptions, risk ratio (95%CI) 0.17 (0.05-0.53), p = 0.002; and increased minimum oxygen saturation, mean difference (95%CI) 4.1 (2.70-5.50), p < 0.001; as compared with the control group. High-flow nasal oxygen had no impact on hypercarbia, risk ratio (95%CI) 1.24 (0.97-1.58), p = 0.09, I2 = 0%. High-flow nasal oxygen reduced the incidence of hypoxaemia regardless of the procedure involved, degree of fractional inspired oxygen, risk-profile of patients and mode of propofol administration. The evidence was ascertained as moderate for all outcomes except for procedure interruptions. In summary, high-flow nasal oxygen compared with conventional oxygenation techniques reduced the risk of hypoxaemia, increased minimum oxygen saturation and reduced the requirement for airway manoeuvres. High-flow nasal oxygen should be considered in patients at risk of hypoxaemia during procedural sedation.

Evidence-based Canadian guidelines for tele-retina screening for diabetic retinopathy: recommendations from the Canadian Retina Research Network (CR2N) Tele-Retina Steering Committee.

OBJECTIVE: The purpose of this report is to develop a consensus for Canadian national guidelines specific to a tele-medicine approach to screening for diabetic retinopathy (DR) using evidence-based and clinical data. METHODS: Canadian Tele-Screening Grading Scales for DR and diabetic macular edema (DME) were created primarily based on severity grading scales outlined by the International Clinical Diabetic Retinopathy Disease Severity Scale (ICDR) and the Scottish DR Grading Scheme 2007. Other grading scales used in international screening programs and the clinical expertise of the Canadian Retina Research Network members and retina specialists nationwide were also used in the creation of the guidelines. RESULTS: National Tele-Screening Guidelines for DR and DME with and without optical coherence tomography (OCT) images are proposed. These outline a diagnosis and management algorithm for patients presenting with different stages of DR and/or DME. General guidelines detailing the requirements for imaged retina fields, image quality, quality control, and follow-up care and the role of visual acuity, pupil dilation, OCT, ultra-wide-field imaging, and artificial intelligence are discussed. CONCLUSIONS: Tele-retina screening can help to address the need for timely and effective screening for DR, whose prevalence continues to rise. A standardized and evidence-based national approach to DR tele-screening has been proposed, based on DR/DME grading using two 45° image fields or a single widefield or ultra-wide-field image, preferable use of OCT imaging, and a focus on local quality control measures.

Role of Saliva and Salivary Diagnostics in the Advancement of Oral Health.

The objective of this article was to provide an account of some of the developments related to saliva over the first 100 years of the Journal of Dental Research and to outline some of the many biomarkers identified in saliva in the last few years. The first section covers findings in salivary physiology, biochemistry, calcium phosphate chemistry related to saliva, microbiology, and the role of saliva in maintaining oral health. The second section highlights salivary diagnostics, salivaomics, and saliva exosomics in the context of the emerging theme of personalized and precision medicine.

Human tRNA-Derived Small RNAs Modulate Host-Oral Microbial Interactions.

Coevolution of the human host and its associated microbiota has led to sophisticated interactions to maintain a delicate homeostasis. Emerging evidence suggests that in addition to small molecules, peptides, and proteins, small regulatory noncoding RNAs (sRNAs) might play an important role in cross-domain interactions. In this study, we revealed the presence of diverse host transfer RNA-derived small RNAs (tsRNAs) among human salivary sRNAs. We selected 2 tsRNAs (tsRNA-000794 and tsRNA-020498) for further study based on their high sequence similarity to specific tRNAs from a group of Gram-negative oral bacteria, including Fusobacterium nucleatum, a key oral commensal and opportunistic pathogen. We showed that the presence of F. nucleatum triggers exosome-mediated release of tsRNA-000794 and tsRNA-020498 by human normal oral keratinocyte cells. Furthermore, both tsRNA candidates exerted a growth inhibition effect on F. nucleatum, likely through interference with bacterial protein biosynthesis, but did not affect the growth of Streptococcus mitis, a health-associated oral Gram-positive bacterium whose genome does not carry sequences bearing high similarity to either tsRNA. Our data provide the first line of evidence for the modulatory role of host-derived tsRNAs in the microbial-host interaction.

Liquid Biopsy in Head and Neck Cancer: Promises and Challenges.

Head and neck cancer is the sixth most common cancer worldwide. It remains one of the leading causes of death, and its early detection is crucial. Liquid biopsy has emerged as a promising tool for detecting and monitoring the disease status of patients with early and advanced cancers. Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal miRNAs have received enormous attention because of their apparent clinical implications. Analyses of these circulating biomarkers have paved the way for novel therapeutic approaches and precision medicine. A growing number of reports have implicated the use of circulating biomarkers for detection, treatment planning, response monitoring, and prognosis assessment. Although these new biomarkers can provide a wide range of possible clinical applications, no validated circulating biomarkers have yet been integrated into clinical practice for head and neck cancer. In this review, we summarize the current knowledge of circulating biomarkers in this field, focusing on their feasibility, limitations, and key areas of clinical applications. We also highlight recent advances in salivary diagnostics and their potential application in head and neck cancer.

Emerging horizons of salivary diagnostics for periodontal disease.

The field of salivary diagnostics to allow risk determination for periodontal diseases is advancing. New technologies in proteomics, genomics and nanotechnologies have continued the discovery of discriminatory periodontal disease biomarkers. This review briefly overviews biomarker studies that have been completed in saliva for the detection of periodontal disease since 2010. Disease specific biomarkers could be used in risk determination, treatment planning and disease progression. Currently, diagnostic tests are commercially available, and the development of point-of-care tests is expanding. Even though challenges remain, salivary diagnostics for periodontal disease is promising and could facilitate the diagnostics and treatment in a clinical practice by dental practitioners.

Utility of mesenchymal stromal cells for myocardial infarction. Transitioning from bench to bedside.

Amongst experimental therapies being evaluated for myocardial infarction (MI), the field of cellular cardiomyoplasty still provokes much excitement, well into its second decade of investigation. Mesenchymal stromal/stem cells (MSCs) have held a particularly enduring place as one of the mainstays of adult-derived stem cell research in cardiovascular disease. These rare, non-hematopoietic cells are natively present throughout different postnatal tissues, most famously bone marrow, where they typically participate in perivascular stem cell niches and play key supportive and trophic roles. Their application for exogenous stem cell delivery is made attractive by their ease of isolation, proclivity for ex vivo expansion and potential for allogeneic use. There is now a remarkable wealth of in vitro and animal-based evidence attesting to the ability of MSCs to safely augment cardiac repair post-MI through pleiotropic mechanisms that continue to be delineated and in turn, optimised. However, despite such preclinical promise and the encouraging results of preliminary experience in human patients, the broader translation of MSCs to the clinical cardiovascular realm requires much more refinement to overcome fundamental limitations, not to mention rigorous validation to resolve lingering areas of uncertainty. Here we review the basic biological properties that have made MSCs so widely investigated for cardiovascular repair, discuss the preclinical evidence for their efficacy and purported mechanisms of action and consider the practicalities and evidence for their use in human patients with MI and cardiomyopathy.

Cardiac magnetic resonance, transthoracic and transoesophageal echocardiography: a comparison of in vivo assessment of ventricular function in rats.

In vivo assessment of ventricular function in rodents has largely been restricted to transthoracic echocardiography (TTE). However 1.5 T cardiac magnetic resonance (CMR) and transoesophageal echocardiography (TOE) have emerged as possible alternatives. Yet, to date, no study has systematically assessed these three imaging modalities in determining ejection fraction (EF) in rats. Twenty rats underwent imaging four weeks after surgically-induced myocardial infarction. CMR was performed on a 1.5 T scanner, TTE was conducted using a 9.2 MHz transducer and TOE was performed with a 10 MHz intracardiac echo catheter. Correlation between the three techniques for EF determination and analysis reproducibility was assessed. Moderate-strong correlation was observed between the three modalities; the greatest between CMR and TOE (intraclass correlation coefficient (ICC) = 0.89), followed by TOE and TTE (ICC = 0.70) and CMR and TTE (ICC = 0.63). Intra- and inter-observer variations were excellent with CMR (ICC = 0.99 and 0.98 respectively), very good with TTE (0.90 and 0.89) and TOE (0.87 and 0.84). Each modality is a viable option for evaluating ventricular function in rats, however the high image quality and excellent reproducibility of CMR offers distinct advantages even at 1.5 T with conventional coils and software.

Anaemia in chronic heart failure: more awareness is required.

AIMS: To determine the characteristics of anaemic patients, how well anaemia is investigated and its contributing factors in patients with chronic heart failure (CHF). METHODS: Retrospective analysis of longitudinal data collected during routine management of patients admitted with CHF at an Australian tertiary hospital. One thousand and twenty-one patients admitted with CHF between 1997 and 2005 were included. Anaemia was defined as a haemoglobin concentration <110 g/L. Data were compared between anaemic and non-anaemic patients. RESULTS: The prevalence of anaemia among patients with CHF was 20.3% in our study. These patients were more likely to be older, female, and have a higher prevalence of chronic renal failure and peripheral vascular disease. Despite previous studies reporting a higher mortality rate among CHF patients with anaemia, only 60% of patients had basic investigations for anaemia (i.e. iron studies, vitamin B12, folate and thyroid function testing). The cause of anaemia is usually multifactorial with 63.8% of patients having at least two factors contributing to their anaemia. Chronic renal failure, iron deficiency and anaemia of chronic disease were the most common contributors. These factors were not predicted based on abnormalities in mean corpuscular volume. Patients with anaemia had a longer length of stay in hospital. CONCLUSIONS: Anaemia in patients with CHF is common but not well investigated. The aetiology of anaemia is usually multifactorial and not easily predicted. Patients with anaemia and CHF have poorer outcomes. There needs to be more awareness among clinicians about the importance of investigating and treating anaemia in patients with CHF.

The usage of the Boussignac continuous positive airway pressure system in acute respiratory failure.

Traditionally, continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) devices have been used to treat patients in acute respiratory failure. However they require an electric power source, are relatively large in size, and may be difficult to use in prehospital settings. The recently introduced Boussignac CPAP system is capable of delivering 10 cmH2O of CPAP, is compact, portable and requires only an oxygen source. This paper reviews the efficacy of using Boussignac CPAP as a treatment for acute respiratory failure in both prehospital and hospital settings. All studies mainly focused on patients treated for cardiogenic pulmonary edema. In the prehospital setting, Boussigac CPAP significantly improved respiratory parameters and oxygenation from baseline values. In the emergency department setting, Boussignac CPAP was more effective than standard oxygen delivery and just as effective as BiPAP in improving patient oxygenation and respiration. In one study, implementing Boussignac CPAP reduced intubation rate and hospital stay. Most hospital staff found Boussignac CPAP easy to use and complication rates were low. Boussigac CPAP is a useful device in the treatment of patients with acute respiratory failure, especially in the prehospital setting.

Mallampati class does not affect the success rate of intubation through an intubating laryngeal mask airway with reverse tracheal tube direction.

BACKGROUND: The aim of this paper was to assess whether the Mallampati class can affect the success rate of intubation through an intubating laryngeal mask airway (ILMA) with a reverse conventional tracheal tube direction. METHODS: Two-hundred ASA I-II adults, 100 patients with Mallampati class 1 or 2 (MP12) and 100 with Mallampati class 3 or 4 (MP34) undergoing elective surgery under general anesthesia were enrolled. All the patients were intubated through the ILMA with a reverse conventional tracheal tube direction. Tracheal intubation was considered successful if proper tracheal positioning was attained within three attempts. Chi-Square analysis was used to compare categorical variables between the two groups. RESULTS: Tracheal intubation was successful in 186 of 200 patients (93.0%): 169 (84.5%) at the first attempt. Fourteen (7.0%) had to be intubated using direct laryngoscope. Both the first attempt success rate and overall success rate were similar between the MP12 and MP34 groups (84.0 vs. 85.0%, P=0.845 and 93.0 vs. 93.0%, respectively). CONCLUSION: Tracheal intubation was successful in 93.0% of patients through an ILMA with a reverse conventional tracheal tube. Mallampati class did not affect the success rate of intubation.

The LMA-Supreme™ as an intubation conduit in patients with known difficult airways: a prospective evaluation study.

BACKGROUND: Many extraglottic airway devices allow the direct passage of an adult-sized tracheal tube, but this is not possible with the LMA-Supreme(TM) . We evaluated the feasibility of using the LMA-Supreme(TM) as a conduit for intubation in patients with known difficult airways. METHODS: Sixty-eight adult patients, with preoperative predictors of difficult intubation, were scheduled for elective surgery under general anaesthesia. After assessing the direct laryngoscopy view, 23 patients with Cormack-Lehane III/IV were included in the study. An LMA-Supreme(TM) was inserted, followed by the passage of a flexible bronchoscope loaded with an Aintree Intubation Catheter into the trachea. The bronchoscope and LMA-Supreme(TM) were removed, and a tracheal tube was railroaded over the Aintree Intubation Catheter into the trachea. RESULTS: Tracheal intubation was successful in all patients using the above technique. SpO(2) was >95% during the intubation procedure. CONCLUSIONS: We conclude that the LMA-Supreme(TM) is a successful conduit for bronchoscopic/Aintree Intubation Catheter-guided intubation in patients with known difficult airway.

Salivary diagnostics.

Saliva is a noninvasive and accessible biofluid that permits early detection of oral and systemic diseases. Recent scientific and technologic advances have uncovered specific salivary biomarkers for a number of clinical conditions, including cancers, autoimmune diseases, and cardiovascular disorders. The availability of highly sensitive and high-throughput assays such as microarray, mass spectrometry, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and nano-scale sensors that can measure proteins and nucleic acids are poising saliva as an emerging biofluid for translational and clinical applications. This paper will discuss development of salivary biomarkers for the detection of oral and systemic diseases and the translational application of these markers for clinical applications.

Defining intact protein primary structures from saliva: a step toward the human proteome project.

Top-down mass spectrometry has been used to investigate structural diversity within some abundant salivary protein families. In this study, we report the identification of two isoforms of protein II-2 which differed in mass by less than 1 Da, the determination of a sequence for protein IB8a that was best satisfied by including a mutation and a covalent modification in the C-terminal part, and the assignment of a sequence of a previously unreported protein of mass 10433 Da. The final characterization of Peptide P-J was achieved, and the discovery of a truncated form of this peptide was reported. The first sequence assignment was done at low resolution using a hybrid quadrupole time-of-flight instrument to quickly identify and characterize proteins, and data acquisition was switched to Fourier-transform ion cyclotron resonance (FTICR) for proteins that required additional sequence coverage and certainty of assignment. High-resolution and high mass accuracy mass spectrometry on a FTICR-mass spectrometry (MS) instrument combined with electron-capture dissociation (ECD) provided the most informative data sets, with the more frequent presence of "unique" ions that unambiguously define the primary structure. A mixture of predictable and unusual post-translational modifications in the protein sequence precluded the use of shotgun-annotated databases at this stage, requiring manual iterations of sequence refinement in many cases. This led us to propose guidelines for an iterative processing workflow of MS and MSMS data sets that allow researchers to completely assign the identity and the structure of a protein.

Double edge: CDK2AP1 in cell-cycle regulation and epigenetic regulation.

Cancer research has been devoted toward an understanding of the molecular regulation and functional significance of cell-cycle regulators in the pathogenesis and development of cancers. Cyclin-dependent Kinase 2-associated Protein 1 (CDK2AP1) is one such cell-cycle regulator, originally identified as a growth suppressor and a prognostic marker for human oral/head and neck cancers. Functional importance and the molecular mechanism of CDK2AP1-mediated cell-cycle regulation have been documented over the years. Recent progress has shown that CDK2AP1 is a competency factor in embryonic stem cell differentiation. Deletion of CDK2AP1 leads to early embryonic lethality, potentially through altered differentiation capability of embryonic stem cells. More intriguingly, CDK2AP1 exerts its effect on stem cell maintenance/differentiation through epigenetic regulation. Cancer cells and stem cells share common cellular characteristics, most prominently in maintaining high proliferative potential through an unconventional cell-cycle regulatory mechanism. Cross-talk between cellular processes and molecular signaling pathways is frequent in any biological system. Currently, it remains largely elusive how cell-cycle regulation is mechanistically linked to epigenetic control. Understanding the molecular mechanism underlying CDK2AP1-mediated cell-cycle regulation and epigenetic control will set an example for establishing a novel and effective molecular link between these two important regulatory mechanisms.

Saliva, diagnostics, and dentistry.

Saliva, a scientific and clinical entity familiar to every oral health researcher and dental practitioner, has emerged as a translational and clinical commodity that has reached national visibility at the National Institutes of Health and the President's Office of Science and Technology. "Detecting dozens of diseases in a sample of saliva" was issued by President Obama as one of the 14 Grand Challenges for biomedical research in the 21(st) Century (National Economic Council, 2010). In addition, NIH's 2011 Government Performance Report Act (GPRA) listed 10 initiatives in the high-risk long-term category (Collins, 2011). The mandate is to determine the efficacy of using salivary diagnostics to monitor health and diagnose at least one systemic disease by 2013. The stage is set for the scientific community to capture these national and global opportunities to advance and substantiate the scientific foundation of salivary diagnostics to meet these goals. A specific calling is to the oral, dental, and craniofacial health community. Three areas will be highlighted in this paper: the concept of high-impact diagnostics, the role of dentists in diagnostics, and, finally, an infrastructure currently being developed in the United Kingdom--The UK Biobank--which will have an impact on the translational and clinical utilizations of saliva.

Scientific frontiers: emerging technologies for salivary diagnostics.

Saliva, a biofluid historically well-studied biochemically and physiologically, has entered the post-genomic 'omics' era, where its proteomic, genomic, and microbiome constituents have been comprehensively deciphered. The translational path of these salivary constituents has begun toward a variety of personalized individual medical applications, including early detection of cancer. Salivary diagnostics is a late-comer, but it is catching up where dedicated resources, like the Salivaomics Knowledge Base (SKB), now have taken center stage in the dissemination of the diagnostic potentials of salivary biomarkers and other translational and clinical utilities.