Mismatch between Tissue Partial Oxygen Pressure and Near-Infrared Spectroscopy Neuromonitoring of Tissue Respiration in Acute Brain Trauma: The Rationale for Implementing a Multimodal Monitoring Strategy.

The brain tissue partial oxygen pressure (PbtO2) and near-infrared spectroscopy (NIRS) neuromonitoring are frequently compared in the management of acute moderate and severe traumatic brain injury patients; however, the relationship between their respective output parameters flows from the complex pathogenesis of tissue respiration after brain trauma. NIRS neuromonitoring overcomes certain limitations related to the heterogeneity of the pathology across the brain that cannot be adequately addressed by local-sample invasive neuromonitoring (e.g., PbtO2 neuromonitoring, microdialysis), and it allows clinicians to assess parameters that cannot otherwise be scanned. The anatomical co-registration of an NIRS signal with axial imaging (e.g., computerized tomography scan) enhances the optical signal, which can be changed by the anatomy of the lesions and the significance of the radiological assessment. These arguments led us to conclude that rather than aiming to substitute PbtO2 with tissue saturation, multiple types of NIRS should be included via multimodal systemic- and neuro-monitoring, whose values then are incorporated into biosignatures linked to patient status and prognosis. Discussion on the abnormalities in tissue respiration due to brain trauma and how they affect the PbtO2 and NIRS neuromonitoring is given.

Tomographic Task-Related Functional Near-Infrared Spectroscopy in Acute Sport-Related Concussion: An Observational Case Study.

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed.

Frequency-domain vs continuous-wave near-infrared spectroscopy devices: a comparison of clinically viable monitors in controlled hypoxia.

The Near-infrared spectroscopy (NIRS) has not been adopted as a mainstream monitoring modality in acute neurosurgical care due to concerns about its reliability and consistency. However, improvements in NIRS parameter recovery techniques are now available that may improve the quantitative accuracy of NIRS for this clinical context. Therefore, the aim of this study was to compare the abilities of a continuous-wave (CW) NIRS device with a similarly clinically viable NIRS device utilising a frequency-domain (FD) parameter recovery technique in detecting changes in cerebral tissue saturation during stepwise increases of experimentally induced hypoxia. Nine healthy individuals (6M/3F) underwent a dynamic end-tidal forced manipulation of their expiratory gases to induce a stepwise induced hypoxia. The minimum end-tidal oxygen partial pressure (EtO2) achieved was 40 mm Hg. Simultaneous neurological and extra-cranial tissue NIRS reading were obtained during this protocol by both tested devices. Both devices detected significant changes in cerebral tissue saturation during the induction of hypoxia (CW 9.8 ± 2.3 %; FD 7.0 ± 3.4 %; Wilcoxon signed rank test P < 0.01 for both devices). No significant difference was observed between the saturation changes observed by either device (P = 0.625). An observably greater degree of noise was noticed in parameters recovered by the FD device, and both demonstrated equally variable baseline readings (Coefficient of variance 8.4 and 9.7 % for the CW and FD devices, respectively) between individuals tested. No advantageous difference was observed in parameters recovered from the FD device compared with those detected by CW.

Bone Flap Technique for Impacted Teeth Extraction and Bone Cysts Removal.

The treatment of cystic lesions and the extraction of impacted third molars are 2 of the most common procedures in oral and maxillofacial surgery. The surgical treatment of cysts of the jaws can consist of a cystectomy, a cystotomy, or a staged combination of the 2 procedures. The surgical techniques developed for the extraction of impacted third molars are: coronectomy, orthodontic extraction, and surgery using intraoral or extraoral methods. There are various complications related to both surgical treatments. With regards to these complications, authors' department has developed a new surgical technique based on a previously described technique, which provides better support to the mucoperiosteal flap and improves bone regeneration after healing. Additionally, authors' goal was to reduce the risk of nerve injury, which has been achieved thanks to a direct visualization of the inferior alveolar nerve as well as cystic lesion or the dental element. The surgical procedure described produces major advantages over the traditional alternatives, despite needing a longer operation. This technique is particularly useful in the treatment of cystic lesions that have caused considerable bone loss. It can also be utilized for cysts or impacted dental elements strictly linked to the inferior alveolar nerve.

Pulmonary shunt in critical care: a practical approach with clinical scenarios.

BACKGROUND: Pulmonary shunt refers to the passage of venous blood into the arterial blood system bypassing the alveoli-blood gas exchange. Pulmonary shunt is defined by a drop in the physiologic coupling of lung ventilation and lung perfusion. This may consequently lead to respiratory failure. MAIN BODY: The pulmonary shunt assessment is often neglected. From a mathematical point of view, pulmonary shunt can be assessed by estimating the degree of mixing between oxygenated and deoxygenated blood. To compute the shunt, three key components are analyzed: the oxygen (O2) content in the central venous blood before gas exchange, the calculated O2 content in the pulmonary capillaries after gas exchange, and the O2 content in the arterial system, after the mixing of shunted and non-shunted blood. Computing the pulmonary shunt becomes of further importance in patients on extracorporeal membrane oxygenation (ECMO), as arterial oxygen levels may not directly reflect the gas exchange of the native lung. CONCLUSION: In this review, the shunt analysis and its practical clinical applications in different scenarios are discussed by using an online shunt simulator.

Photobiomodulation reduces hippocampal apoptotic cell death and produces a Raman spectroscopic "signature".

Apoptotic cell death within the brain represents a significant contributing factor to impaired post-traumatic tissue function and poor clinical outcome after traumatic brain injury. After irradiation with light in the wavelength range of 600-1200 nm (photobiomodulation), previous investigations have reported a reduction in apoptosis in various tissues. This study investigates the effect of 660 nm photobiomodulation on organotypic slice cultured hippocampal tissue of rats, examining the effect on apoptotic cell loss. Tissue optical Raman spectroscopic changes were evaluated. A significantly higher proportion of apoptotic cells 62.8±12.2% vs 48.6±13.7% (P<0.0001) per region were observed in the control group compared with the photobiomodulation group. After photobiomodulation, Raman spectroscopic observations demonstrated 1440/1660 cm-1 spectral shift. Photobiomodulation has the potential for therapeutic utility, reducing cell loss to apoptosis in injured neurological tissue, as demonstrated in this in vitro model. A clear Raman spectroscopic signal was observed after apparent optimal irradiation, potentially integrable into therapeutic light delivery apparatus for real-time dose metering.

Multi-laboratory performance assessment of diffuse optics instruments: the BitMap exercise.

SIGNIFICANCE: Multi-laboratory initiatives are essential in performance assessment and standardization-crucial for bringing biophotonics to mature clinical use-to establish protocols and develop reference tissue phantoms that all will allow universal instrument comparison. AIM: The largest multi-laboratory comparison of performance assessment in near-infrared diffuse optics is presented, involving 28 instruments and 12 institutions on a total of eight experiments based on three consolidated protocols (BIP, MEDPHOT, and NEUROPT) as implemented on three kits of tissue phantoms. A total of 20 synthetic indicators were extracted from the dataset, some of them defined here anew. APPROACH: The exercise stems from the Innovative Training Network BitMap funded by the European Commission and expanded to include other European laboratories. A large variety of diffuse optics instruments were considered, based on different approaches (time domain/frequency domain/continuous wave), at various stages of maturity and designed for different applications (e.g., oximetry, spectroscopy, and imaging). RESULTS: This study highlights a substantial difference in hardware performances (e.g., nine decades in responsivity, four decades in dark count rate, and one decade in temporal resolution). Agreement in the estimates of homogeneous optical properties was within 12% of the median value for half of the systems, with a temporal stability of <5 % over 1 h, and day-to-day reproducibility of <3 % . Other tests encompassed linearity, crosstalk, uncertainty, and detection of optical inhomogeneities. CONCLUSIONS: This extensive multi-laboratory exercise provides a detailed assessment of near-infrared Diffuse optical instruments and can be used for reference grading. The dataset-available soon in an open data repository-can be evaluated in multiple ways, for instance, to compare different analysis tools or study the impact of hardware implementations.

Dynamic contrast-enhanced near-infrared spectroscopy using indocyanine green on moderate and severe traumatic brain injury: a prospective observational study.

BACKGROUND: The care given to moderate and severe traumatic brain injury (TBI) patients may be hampered by the inability to tailor their treatments according to their neurological status. Contrast-enhanced near-infrared spectroscopy (NIRS) with indocyanine green (ICG) could be a suitable neuromonitoring tool. METHODS: Monitoring the effective attenuation coefficients (EAC), we compared the ICG kinetics between five TBI and five extracranial trauma patients, following a venous-injection of 5 mL of 1 mg/mL ICG, using two commercially available NIRS devices. RESULTS: A significantly slower passage of the dye through the brain of the TBI group was observed in two parameters related to the first ICG inflow into the brain (P=0.04; P=0.01). This is likely related to the reduction of cerebral perfusion following TBI. Significant changes in ICG optical properties minutes after injection (P=0.04) were registered. The acquisition of valid optical data in a clinical environment was challenging. CONCLUSIONS: Future research should analyze abnormalities in the ICG kinetic following brain trauma, test how these values can enhance care in TBI, and adapt the current optical devices to clinical settings. Also, studies on the pattern in changes of ICG optical properties after venous injection can improve the accuracy of the values detected.

The Valsalva maneuver: an indispensable physiological tool to differentiate intra versus extracranial near-infrared signal.

Developing near-infrared spectroscopy (NIRS) parameter recovery techniques to more specifically resolve brain physiology from that of the overlying tissue is an important part of improving the clinical utility of the technology. The Valsalva maneuver (VM) involves forced expiration against a closed glottis causing widespread venous congestion within the context of a fall in cardiac output. Due to the specific anatomical confines and metabolic demands of the brain we believe a properly executed VM has the ability to separate haemodynamic activity of brain tissue from that of the overlying scalp as observed by NIRS, and confirmed by functional magnetic resonance imaging (fMRI). Healthy individuals performed a series of standing maximum effort VMs under separate observation by frequency domain near-infrared spectroscopy (FD-NIRS) and fMRI. Nine individuals completed the clinical protocol (6 males, age 21-40). During the VMs, brain and extracranial tissue targeted signal were significantly different (opposite direction of change) in both fMRI and NIRS (p=0.00025 and 0.00115 respectively), with robust cross correlation of parameters between modalities. Four of these individuals performed further VMs after infiltrating 2% xylocaine/1:100,000 epinephrine (vasoconstrictor) into scalp tissue beneath the probes. No significant difference in the cerebrally derived parameters was observed. The maximum effort VM has the ability to separate NIRS observable physiology of the brain from the overlying extracranial tissue. Observations made by this FD cerebral NIRS device are comparable with fMRI in this context.

Cerebral perfusion and blood-brain barrier assessment in brain trauma using contrast-enhanced near-infrared spectroscopy with indocyanine green: A review.

Contrast-enhanced near-infrared spectroscopy (NIRS) with indocyanine green (ICG) can be a valid non-invasive, continuous, bedside neuromonitoring tool. However, its usage in moderate and severe traumatic brain injury (TBI) patients can be unprecise due to their clinical status. This review is targeted at researchers and clinicians involved in the development and application of contrast-enhanced NIRS for the care of TBI patients and can be used to design future studies. This review describes the methods developed to monitor the brain perfusion and the blood-brain barrier integrity using the changes of diffuse reflectance during the ICG passage and the results on studies in animals and humans. The limitations in accuracy of these methods when applied on TBI patients and the proposed solutions to overcome them are discussed. Finally, the analysis of relative parameters is proposed as a valid alternative over absolute values to address some current clinical needs in brain trauma care. In conclusion, care should be taken in the translation of the optical signal into absolute physiological parameters of TBI patients, as their clinical status must be taken into consideration. Discussion on where and how future studies should be directed to effectively incorporate contrast-enhanced NIRS into brain trauma care is given.

Cerebral Oxygenation in Traumatic Brain Injury: Can a Non-Invasive Frequency Domain Near-Infrared Spectroscopy Device Detect Changes in Brain Tissue Oxygen Tension as Well as the Established Invasive Monitor?

The cost and highly invasive nature of brain monitoring modality in traumatic brain injury patients currently restrict its utility to specialist neurological intensive care settings. We aim to test the abilities of a frequency domain near-infrared spectroscopy (FD-NIRS) device in predicting changes in invasively measured brain tissue oxygen tension. Individuals admitted to a United Kingdom specialist major trauma center were contemporaneously monitored with an FD-NIRS device and invasively measured brain tissue oxygen tension probe. Area under the curve receiver operating characteristic (AUROC) statistical analysis was utilized to assess the predictive power of FD-NIRS in detecting both moderate and severe hypoxia (20 and 10 mm Hg, respectively) as measured invasively. Sixteen individuals were prospectively recruited to the investigation. Severe hypoxic episodes were detected in nine of these individuals, with the NIRS demonstrating a broad range of predictive abilities (AUROC 0.68-0.88) from relatively poor to good. Moderate hypoxic episodes were detected in seven individuals with similar predictive performance (AUROC 0.576-0.905). A variable performance in the predictive powers of this FD-NIRS device to detect changes in brain tissue oxygen was demonstrated. Consequently, this enhanced NIRS technology has not demonstrated sufficient ability to replace the established invasive measurement.

Investigation into repetitive concussion in sport (RECOS): study protocol of a prospective, exploratory, observational cohort study.

INTRODUCTION: Sport-related concussion management remains a diagnostic dilemma to clinicians in all strata of care, coaching staff and players alike. The lack of objective diagnostic and prognostic biomarkers and over-reliance on subjective clinical assessments carries a significant health risk of undiagnosed concussive episodes and early return to play before full recovery increasing the risk of sustaining additional concussion, and leading to long-term sequelae and/or unfavourable outcome. OBJECTIVE: To identify a set of parameters (neuroimaging with neurophysiological, biological and neuropsychological tests) that may support pitch-side and outpatient clinical decision-making in order to objectively diagnose concussion, determine the severity of injury, guide a safe return to play and identify the potential predictors of the long-term sequelae of concussion. METHODS AND ANALYSIS: An exploratory, observational, prospective, cohort study recruiting between 2017 and 2020. The participants will have a baseline preseason screening (brain imaging, neuropsychological assessments, serum, urine and saliva sampling). If a screened player later suffers a concussion and/or multiple concussions then he/she will be assessed again with the same protocol within 72 hours, and their baseline data will be used as internal control as well as normative data. Inferential statistical analysis will be performed to determine correlations between biological, imaging techniques and neuropsychological assessments. ETHICS AND DISSEMINATION: This study was approved by the East of England-Essex Research Ethics Committee on 22 September 2017-REC 17/EE/0275; IRAS 216703. The results of this study will be presented at national and international conferences and submitted for publication in peer reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN16974791; Pre-results.

Salivary MicroRNAs: Diagnostic Markers of Mild Traumatic Brain Injury in Contact-Sport.

Concussion is difficult to diagnose, particularly when symptoms are atypical or late in presenting. An accurate and timely initial assessment is crucial for clinical management. Cerebral spinal fluid (CSF) and blood markers of traumatic brain injury show promising results but their clinical applicability in concussion has significant limitations. In the study, we explored saliva as a new source of biomarkers of concussion. Saliva samples of concussed players were collected after 48-72 h from concussion and analyzed by high-throughput technologies. A discovery group of 10 concussed rugby professional and semiprofessional athletes and 10 non-concussed matched controls was used for the analysis of 92 inflammatory proteins by the Proseek-Multiplex-Inflammation technology. In addition, saliva samples of 6 concussed and 6 non-concussed athletes were used to screen 800 human microRNAs (miRNAs) by the Nanostring Technology. The results were then validated by RT-qPCR in an enlarged cohort (validation group) comprising 22 concussed athletes. Results showed, no significant variations of the 65 inflammatory proteins detected in saliva between groups but 5 microRNAs, miR-27b-3p (p = 0.016), let-7i-5p (p = 0.001), miR-142-3p (p = 0.008), miR-107 (p = 0.028), miR-135b-5p (p = 0.017) significantly upregulated in concussed athletes. Univariate ROC curve analysis showed that the differentially expressed miRNAs could be considered good classifiers of concussion. Further analyses showed significant correlation between these microRNAs and Reaction Time component of the ImPACT concussion assessment tool. In addition, biocomputation analysis predicted the involvement of these microRNAs in important biological processes that might be related to trauma, such as response to hypoxia, cell death, neurogenesis, axon repair and myelination. Ease of access and non-invasiveness of saliva samples make these biomarkers particularly suitable for concussion assessment.

Study of Concussion in Rugby Union through MicroRNAs (SCRUM): a study protocol of a prospective, observational cohort study.

INTRODUCTION: The diagnosis of mild traumatic brain injury or sports-related concussion is a challenge for all clinicians, players, coaches and parents involved in contact sports. Currently, there is no validated objective biomarker available to assess the presence or severity of concussion in sport, and so it is necessary to rely on subjective measures like self-reporting of symptoms which depend on the cooperation of the athlete. There is a significant health risk associated with repetitive injury if the diagnosis is missed, and so there is great value in an objective biomarker to assist diagnostic and prognostic decisions. OBJECTIVE: To establish a panel of non-invasive MicroRNA biomarkers in urine and saliva for the rapid diagnosis of sports-related concussion and investigate the kinetics and clinical utility of these biomarkers in assisting diagnostic, prognostic and return-to-play decisions. METHODS AND ANALYSIS: Observational, prospective, multicentre cohort study recruiting between the 2017-2018 and 2018-2019 Rugby Union seasons. Professional rugby players in the two highest tiers of senior professional domestic rugby competition in England will be recruited prospectively to the study. During the season, three groups will be identified: athletes entering the World Rugby Head Injury Assessment (HIA) protocol, uninjured control athletes and control athletes with musculoskeletal injuries. Saliva and urine will be collected from these athletes at multiple timepoints, coinciding with key times in the HIA protocol and return-to-play process. ETHICS AND DISSEMINATION: Ethics approval has been obtained. The compiled and analysed results will be presented at national and international conferences concerning the care of patients with traumatic brain injury. Results will also be submitted for peer review and publication in the subject journals/literature.

Alveolar Ridge Split Technique Using Piezosurgery with Specially Designed Tips.

The treatment of patients with atrophic ridge who need prosthetic rehabilitation is a common problem in oral and maxillofacial surgery. Among the various techniques introduced for the expansion of alveolar ridges with a horizontal bone deficit is the alveolar ridge split technique. The aim of this article is to give a description of some new tips that have been specifically designed for the treatment of atrophic ridges with transversal bone deficit. A two-step piezosurgical split technique is also described, based on specific osteotomies of the vestibular cortex and the use of a mandibular ramus graft as interpositional graft. A total of 15 patients were treated with the proposed new tips by our department. All the expanded areas were successful in providing an adequate width and height to insert implants according to the prosthetic plan and the proposed tips allowed obtaining the most from the alveolar ridge split technique and piezosurgery. These tips have made alveolar ridge split technique simple, safe, and effective for the treatment of horizontal and vertical bone defects. Furthermore the proposed piezosurgical split technique allows obtaining horizontal and vertical bone augmentation.

Ameloblastic carcinoma of the maxilla: A case report and an updated review of the literature.

Ameloblastic carcinoma (AC) is an uncommon malignant odontogenic tumor that can be difficult to differentiate from ameloblastoma and can arise directly as an undifferentiated lesion or from a pre-existing benign lesion. The current study presents a novel case of primary maxillary AC and review the literature on AC of the maxilla. The review of the literature indicates that secondary tumors and posterior localization are associated with a higher tendency for recurrence and, often, multiple recurrences. Surgical therapy, eventually followed by radiotherapy, is the treatment modality most frequently applied, while the role of chemotherapy remains unclear. Several new cases of maxillary AC have been recently described in literature, making this pathology more frequent than previously considered; this is perhaps an indication of an increased diagnostic sensibility, rather than a real increase in the incidence of the disease itself.