Identifying a sublingual triangle as the ideal site for assessment of sublingual microcirculation

The sublingual mucosa is a commonly used intraoral location for identifying microcirculatory alterations using handheld vital microscopes (HVMs). The anatomic description of the sublingual cave and its related training have not been adequately introduced. The aim of this study was to introduce anatomy guided sublingual microcirculatory assessment. Measurements were acquired from the floor of the mouth using incident dark-field (IDF) imaging before (T0) and after (T1) sublingual cave anatomy instructed training. Instructions consists of examining a specific region of interested identified through observable anatomical structures adjacent and bilaterally to the lingual frenulum which is next to the sublingual papilla. The anatomical location called the sublingual triangle, was identified as stationed between the lingual frenulum, the sublingual fold and ventrally to the tongue. Small, large, and total vessel density datasets (SVD, LVD and TVD respectively) obtained by non-instructed and instructed measurements (NIN (T0) and IM (T1) respectively) were compared. Microvascular structures were analyzed, and the presence of salivary duct-related microcirculation was identified. A total of 72 video clips were used for analysis in which TVD, but not LVD and SVD, was higher in IM compared to NIM (NIM vs. IM, 25 ± 2 vs. 27 ± 3 mm/mm$^{2}$ (p = 0.044), LVD NIM vs. IM: 7 ± 1 vs. 8 ± 1mm/mm$^{2}$ (p = 0.092), SVD NIM vs. IM: 18 ± 2 vs. 20 ± 3 mm/mm$^{2}$ (p = 0.103)). IM resulted in microcirculatory assessments which included morphological properties such as capillaries, venules and arterioles, without salivary duct-associated microcirculation. The sublingual triangle identified in this study showed consistent network-based microcirculation, without interference from microcirculation associated with specialized anatomic structures. These findings suggest that the sublingual triangle, an anatomy guided location, yielded sublingual based measurements that conforms with international guidelines. IM showed higher TVD values, and future studies are needed with larger sample sizes to prove differences in microcirculatory parameters

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

Purpose: There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods: Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results: PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780–830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2–3 J (J/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion: PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.National Institutes of Health (U.S.) (NIH grant R01AI050875

Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations

Purpose: There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. Methods: This study is a narrative non-systematic review. Results: We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. Conclusion: Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.National Institutes of Health (U.S.) (grant R01AI050875

Multi-site and multi-depth near-infrared spectroscopy in a model of simulated (central) hypovolemia: lower body negative pressure

Purpose: To test the hypothesis that the sensitivity of near-infrared spectroscopy (NIRS) in reflecting the degree of (compensated) hypovolemia would be affected by the application site and probing depth. We simultaneously applied multi-site (thenar and forearm) and multi-depth (15-2.5 and 25-2.5 mm probe distance) NIRS in a model of simulated hypovolemia: lower body negative pressure (LBNP). Methods: The study group comprised 24 healthy male volunteers who were subjected to an LBNP protocol in which a baseline period of 30 min was followed by a step-wise manipulation of negative pressure in the following steps: 0, -20, -40, -60, -80 and -100 mmHg. Stroke volume and heart rate were measured using volume-clamp finger plethysmography. Two multi-depth NIRS devices were used to measure tissue oxygen saturation (StO2) and tissue hemoglobin index (THI) continuously in the thenar and the forearm. To monitor the shift of blood volume towards the lower extremities, calf THI was measured by single-depth NIRS. Results: The main findings were that the application of LBNP resulted in a significant reduction in stroke volume which was accompanied by a reduction in forearm StO2 and THI. Conclusions: NIRS can be used to detect changes in StO2 and THI consequent upon central hypovolemia. Forearm NIRS measurements reflect hypovolemia more sensitively than thenar NIRS measurements. The sensitivity of these NIRS measurements does not depend on NIRS probing depth. The LBNP-induced shift in blood volume is reflected by a decreased THI in the forearm and an increased THI in the calf

The response of the oral microcirculation to pharmacological and surgical interventions

Dan Milstein beschrijft de gevolgen van farmacologische en chirurgische interventies op de orale microcirculatie. Hij beoordeelde dit door gebruik te maken van sidestream dark-field, een speciaal videomicroscoopsystem. Milstein bekeek de acute dosis afhankelijke respons van de orale mucosale (betrekking hebbend op het slijmvlies) microcirculatie als gevolg van intraveneuze toediening van cytostatica. Ook keek hij naar de groei van bloedvaten na een chirurgisch behandeling. Milstein concludeert onder meer dat door cytostatica opgewekte microcirculatoire respons kan leiden tot een verzadiging van de orale mucosa met cytostatica door toename van de oppervlakte van het blootgestelde gebied. Deze functionele reactie van de microcirculatie op cytostatica zou een bijdrage kunnen leveren bij het tot stand komen van orale complicaties. Ook leidde het toedienen van cytotstatica en de combinatie ervan met een bisfosfonaat tot een significante vertraging van de capillaire regeneratie van het slijmvlies tot na de derde postoperatieve week

Imaging sublingual microcirculatory perfusion in pediatric patients receiving procedural sedation with propofol: A pilot study

Objective: Procedural sedation with propofol is widely used in the pediatric population. A well-known side effect of propofol is a decrease in peripheral vascular resistance resulting in hypotension, but little is known about the effects on microcirculation in humans. We aimed to evaluate the effects of propofol on the sublingual microcirculatory perfusion by continuous video imaging in pediatric patients undergoing procedural sedation. Methods: Patients admitted to the Pediatric Intensive Care Unit for procedural sedation were recruited. Oral microcirculation was measured employing a continuous monitoring strategy with incident dark-field illumination imaging. Measurements were obtained before and 3 minutes after propofol induction. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, blood vessel diameter (Øbv), and systemic hemodynamics were analyzed. Results: Continuous measurements were achieved in seven patients. Three minutes after propofol induction mean arterial pressure decreased (P = 0.028) and total and perfused vessel densities increased by 12% (P = 0.018) and 16% (P = 0.018), respectively. MFI was unaltered and mean Øbv increased but not significantly. Conclusions: Propofol induction induces a reduction in mean arterial pressure and a rise in sublingual microvascular perfusion. The observed effects of propofol on the sublingual microcirculation may be due to a decrease in microvascular resistance

The influence of zoledronic acid and cyclophosphamide on microcirculation regeneration in healing oral mucosal flaps

The use of intravenous nitrogenous bisphosphonates and antineoplastic agents as postoperative adjuvant cancer management strategies may influence the course of oral wound healing by altering tissue vascularisation kinetics. The aim of this study was to investigate if single or combined zoledronic acid (ZOL) and cyclophosphamide (CTX) would influence microcirculation regeneration in healing oral mucosal flaps. Twenty female specific-pathogen free New Zealand white rabbits were randomised into four groups. In all animals a mucosal flap was raised; three groups were treated each separately with intravenous infusions of 0.14mg/kg ZOL, 100mg/kg CTX, or both, respectively. The fourth group was used as a control. Capillary density measurements, expressed as the mean number of capillaries±SD per mm(2) (cpll/mm(2)), was performed preoperatively using sidestream dark-field (SDF) imaging and repeated immediately postoperatively and on days 2, 4, 7, 9, 11, 14, and 21. Whole blood count and body weight was assessed in each group to monitor pharmacotherapeutic responses. Preoperative mean capillary density was 74±8cpll/mm(2) and 40±11cpll/mm(2) directly after surgery (P <0.0001). Post hoc comparisons of follow-up SDF measurements on days 9-21 between control and ZOL vs. CTX and ZOL+CTX were statistically significant (P <0.05). The present study demonstrates that ZOL did not alter capillary regeneration in healing mucosal flaps. However, although the early healing phase is generally characterised by rapid progression of capillary regeneration, interventions with CTX and ZOL+CTX significantly altered capillary regeneration and persisted beyond the third postoperative wee

Microvascular soft tissue changes in alveolar distraction osteogenesis

Objective. The aim of the study was to quantify the effect of distraction osteogenesis on the changes in vascular density in the human oral mucosa. Material and methods. Alveolar distraction was performed in 10 patients with alveolar ridge deficiencies, while in the contralateral nondistracted site an implant was placed. The distraction device was activated after 7 days of latency starting with a distraction rate of 1 mm a day for a 1-week period. After completion of distraction the segments were held in fixation for 6 weeks. Microvascular images were obtained with the use of orthogonal polarization spectral imaging. From day 1 postoperatively until the end of consolidation, microvascular changes in capillary density were assessed. Results. All patients had a good response to the osseous distraction. No dehiscence or infections were observed. In all patients microvascular changes consisted of a bilateral decrease in capillary density and capillary index immediately following surgery. No significant differences between the distraction site and nondistracted implant site were observed during the latency phase or consolidation phase. Capillary vessel count revealed a mean of 14.6 +/- 2.7 vessels per visual field (VF) at day 5 of distraction versus 16.6 +/- 2.9 vessels/VF in the nondistracted site, which increased to a mean of 33.4 +/- 4.0 vessels/VF at day 10 of distraction compared to 24.0 +/- 0.8 vessels/VF in nondistracted implant sites. During the consolidation period the mean number of vessels was comparable to preoperative levels (mean 26.0 vessels/VF). The increase in capillary density and capillary index was more pronounced during the activation phase of distraction compared to the implant site. Conclusion. The increase in vascular response during distraction osteogenesis mainly occurs in the activation phase of distractio

The acute effects of CMF-based chemotherapy on maxillary periodontal microcirculation

A high incidence of oral complications is associated with chemotherapy (CT) treatment in cancer patients; however, while knowledge into molecular mechanisms of their pathobiology continue to evolve, the direct physiological effects of CT on oral tissue perfusion remain unexplored. The aim of this investigation was to assess the acute effects of CT on gingival microcirculation perfusion by measuring gingival capillary density. Twenty female specific-pathogen free New Zealand White rabbits were randomly divided into four groups receiving four different intravenous dose levels of cyclophosphamide, methotrexate, and fluorouracil (CMF). Noninvasive measurements of gingival capillary density were performed using sidestream dark-field (SDF) imaging prior to and 30 min after CT treatment. Four rabbits receiving saline solution were used as control animals. Baseline gingival capillary density was 58 +/- A 11 cpll/mm(2), no significant differences in baseline capillary densities between the groups were found. From low to high dose CT, capillary density 30 min after CMF treatment increased in each group by 1 +/- A 7, 5 +/- A 7, 13 +/- A 18 and 20 +/- A 13 cpll/mm(2), respectively. Capillary density increase was significant in the high-dose group. No change in gingival capillary density was found in the control group. Periodontal microcirculation perfusion had increased 30 min after CT treatment as indicated by a rise in gingival capillary density. Our results support the idea that CT-induced microcirculatory response not only diligently delivers but also saturates peripheral oral tissues with antineoplastic agents by increasing surface area exposure. This functional response of the microcirculation to CT drugs may play a role in contribution to oral complications and the treatment of oral tumor

Alveolar Iodine Tampon Packing Reduces Postoperative Morbidity After Third Molar Surgery

Purpose: The aim of this study was to assess the efficacy of an iodine tampon after mandibular third molar surgery on oral health–related quality of life (OHRQoL), use of painkillers, postoperative sequelae, and self-care behaviors in the first postoperative week. Materials and Methods: This prospective, crossover, randomized controlled study included patients undergoing surgical removal of bilateral symmetrically, horizontally impacted mandibular third molars. The surgical site was randomly allocated to receive an iodine tampon after surgery or wound closure and rinsing with a Monoject syringe (Tyco/Healthcare-Kendall, Mansfield, MA). The primary outcomes measured each day during the first postoperative week were the Oral Health Impact Profile 14 score and postoperative sequelae, including pain, swelling, limited mouth opening, postoperative infection, and alveolar osteitis. The secondary outcome measures were several self-care behaviors. Data were analyzed using repeated-measures analysis of variance and paired-samples t tests. Results: A total of 54 patients (25 men and 29 women; mean age, 25.1 years) were enrolled, with a total of 108 surgically removed impacted mandibular third molars. The use of an iodine tampon resulted in a significantly lower impact on OHRQoL (mean of 21.5 [standard deviation (SD), 9.6] vs 26.5 [SD, 10.6]) on the first postoperative day, which was observable until the seventh postoperative day. In addition, after removal of the impacted third molar, patients with the iodine tampon condition reported less pain (mean of 5.2 [SD, 1.9] vs 6.1 [SD, 2.1] on day 1, lasting throughout the week), less use of painkillers, less limited mouth opening, fewer problems chewing, less swelling, and earlier recovery. Conclusions: The use of postoperative iodine packing after the removal of impacted mandibular third molars significantly reduces OHRQoL and postoperative sequelae