Artificial Intelligence in Medicine: A Caution About Good Intentions and Where It May Lead.

Implementing Artificial Intelligence in medicine is revolutionizing how medicine is practiced. It has much promise in bringing about improved clinical outcomes and efficiency while decreasing costs. There are also concerns and unintended consequences that are being realized and significant efforts to consider ethical principles in the implementation of Artificial Intelligence in medicine. One potential consequence may be the loss of what has been described as the soul of medicine: the physician-patient relationship. This relationship is especially precious in the context of what the US Surgeon General Vivek H. Murthy MD has called an "Epidemic of Loneliness and Isolation." This commentary describes considerations and potential steps to protect this vital relationship while implementing Artificial Intelligence approaches to improving patient care. If not vigilant, Artificial Intelligence may unintentionally erode the physician-patient relationship resulting in physician/patient isolation.

Lateral neck dissection surgeon volume and complications in head and neck endocrine malignancy.

Background: Increased surgeon volume is associated with decreased complications for many surgeries, including thyroidectomy. We sought to use two national databases to assess for associations between surgeon volume and complications in patients undergoing lateral neck dissection for thyroid or parathyroid malignancy. Methods: Lateral neck dissections for thyroid and parathyroid cancer from the Nationwide Inpatient Sample and State Inpatient Database were analyzed. The primary outcome was any inpatient complication common to thyroidectomy, parathyroidectomy, or lateral neck dissection. The principle independent variable was surgeon volume. Multivariable analysis was then performed on this retrospective cohort study. Results: The 1,094 Nationwide Inpatient Sample discharges had a 28% (305/1,094) complication rate. After adjustment, surgeons with volumes between 3-34 neck dissections/year demonstrated a surgeon volume-complication rate association [adjusted odds ratio: 1.03; 95% confidence interval (CI): 1.01-1.05]. The 1,235 State inpatient Database discharges had a 21% (258/1,235) overall complication rate, and no association between surgeon volume and complication rates (P=0.25). Conclusions: This retrospective review of 2,329 discharges for patients undergoing lateral neck dissection for thyroid or parathyroidectomy demonstrated somewhat conflicting results. The Nationwide Inpatient Sample demonstrated increasing complication rates for increasing surgeon volume among intermediate volume surgeons, while the State Inpatient Database demonstrated no surgeon volume-complication association. Given these disparate results, and further limitations with these databases, conclusions regarding surgical volume and clinical decision making based on these data should be assessed cautiously.

Deep-Learning-Based Screening and Ancillary Testing for Thyroid Cytopathology.

Thyroid cancer is the most common malignant endocrine tumor. The key test to assess preoperative risk of malignancy is cytologic evaluation of fine-needle aspiration biopsies (FNABs). The evaluation findings can often be indeterminate, leading to unnecessary surgery for benign post-surgical diagnoses. We have developed a deep-learning algorithm to analyze thyroid FNAB whole-slide images (WSIs). We show, on the largest reported data set of thyroid FNAB WSIs, clinical-grade performance in the screening of determinate cases and indications for its use as an ancillary test to disambiguate indeterminate cases. The algorithm screened and definitively classified 45.1% (130/288) of the WSIs as either benign or malignant with risk of malignancy rates of 2.7% and 94.7%, respectively. It reduced the number of indeterminate cases (N = 108) by reclassifying 21.3% (N = 23) as benign with a resultant risk of malignancy rate of 1.8%. Similar results were reproduced using a data set of consecutive FNABs collected during an entire calendar year, achieving clinically acceptable margins of error for thyroid FNAB classification.

International Collaboration Trends in Facial Plastic and Reconstructive Surgery: A Systematic Bibliometric Scoping Review.

Importance: Research in facial plastic and reconstructive surgery (FPRS) in the global health setting, especially in low- and middle-income countries (LMICs), is increasing year by year. As this work progresses, it will be crucial to include voices and perspectives of individuals living in the LMICs being studied. Objective: To characterize and understand international collaborations in published literature on FPRS care in a global health setting and report patterns in whether these articles included authors from the LMICs in which the studies took place. Evidence Review: A systematic bibliometric scoping review of articles in Scopus from 1971 to 2022 was performed using a set list of search terms; studies were included using predetermined inclusion and exclusion criteria. Studies met criteria for inclusion if the abstract or text contained information regarding surgeons from a different country performing surgery or conducting research in an LMIC within the domain of FPRS. Exclusion criteria were studies that did not mention a facial plastic or reconstructive surgery and studies where both an HIC and LMIC were not mentioned. Findings: A total of 286 studies met criteria for inclusion. The highest percentage of studies (n = 72, 25.2%) were conducted across multiple countries. A total of 120 studies (41.9%) discussed cleft lip/palate. Overall, 141 studies (49.5%) included at least 1 author from the host LMIC; 89 (31.1%) had first authors from LMICs, and 72 (25.2%) had senior authors from LMICs. A total of 79 studies (27.6%) described humanitarian clinical service trips without mentioning research or education in the text. The remaining studies described research, education projects, or a combination. The published literature on humanitarian service trips had the lowest rate of inclusion of a first or senior author from the host LMICs. Conclusions and Relevance: In this systematic bibliometric scoping review, findings showed a general trend of increased international work in the field of FPRS. However, there continues to be a paucity of inclusive authorship trends, with the majority of studies not including first or senior authors from LMICs. The findings presented here encourage new collaborations worldwide, as well as the improvement of existing efforts.

Thyroid Cytopathology Cancer Diagnosis from Smartphone Images Using Machine Learning.

We examined the performance of deep learning models on the classification of thyroid fine-needle aspiration biopsies using microscope images captured in 2 ways: with a high-resolution scanner and with a mobile phone camera. Our training set consisted of images from 964 whole-slide images captured with a high-resolution scanner. Our test set consisted of 100 slides; 20 manually selected regions of interest (ROIs) from each slide were captured in 2 ways as mentioned above. Applying a baseline machine learning algorithm trained on scanner ROIs resulted in performance deterioration when applied to the smartphone ROIs (97.8% area under the receiver operating characteristic curve [AUC], CI = [95.4%, 100.0%] for scanner images vs 89.5% AUC, CI = [82.3%, 96.6%] for mobile images, P = .019). Preliminary analysis via histogram matching showed that the baseline model was overly sensitive to slight color variations in the images (specifically, to color differences between mobile and scanner images). Adding color augmentation during training reduces this sensitivity and narrows the performance gap between mobile and scanner images (97.6% AUC, CI = [95.0%, 100.0%] for scanner images vs 96.0% AUC, CI = [91.8%, 100.0%] for mobile images, P = .309), with both modalities on par with human pathologist performance (95.6% AUC, CI = [91.6%, 99.5%]) for malignancy prediction (P = .398 for pathologist vs scanner and P = .875 for pathologist vs mobile). For indeterminate cases (pathologist-assigned Bethesda category of 3, 4, or 5), color augmentations confer some improvement (88.3% AUC, CI = [73.7%, 100.0%] for the baseline model vs 96.2% AUC, CI = [90.9%, 100.0%] with color augmentations, P = .158). In addition, we found that our model's performance levels off after 15 ROIs, a promising indication that ROI data collection would not be time-consuming for our diagnostic system. Finally, we showed that the model has sensible Bethesda category (TBS) predictions (increasing risk malignancy rate with predicted TBS category, with 0% malignancy for predicted TBS 2 and 100% malignancy for TBS 6).

A Clinical Study to Assess Diffuse Reflectance Spectroscopy with an Auto-Calibrated, Pressure-Sensing Optical Probe in Head and Neck Cancer.

Diffuse reflectance spectroscopy (DRS) is a powerful tool for quantifying optical and physiological tissue properties such as hemoglobin oxygen saturation and vascularity. DRS is increasingly used clinically for distinguishing cancerous lesions from normal tissue. However, its widespread clinical acceptance is still limited due to uncontrolled probe-tissue interface pressure that influences reproducibility and introduces operator-dependent results. In this clinical study, we assessed and validated a pressure-sensing and automatic self-calibration DRS in patients with suspected head and neck squamous cell carcinoma (HNSCC). The clinical study enrolled nineteen patients undergoing HNSCC surgical biopsy procedures. Patients consented to evaluation of this improved DRS system during surgery. For each patient, we obtained 10 repeated measurements on one tumor site and one distant normal location. Using a Monte Carlo-based model, we extracted the hemoglobin saturation data along with total hemoglobin content and scattering properties. A total of twelve cancer tissue samples from HNSCC patients and fourteen normal tissues were analyzed. A linear mixed effects model tested for significance between repeated measurements and compared tumor versus normal tissue. These results demonstrate that cancerous tissues have a significantly lower hemoglobin saturation compared to normal controls (p < 0.001), which may be reflective of tumor hypoxia. In addition, there were minimal changes over time upon probe placement and repeated measurement, indicating that the pressure-induced changes were minimal and repeated measurements did not differ significantly from the initial value. This study demonstrates the feasibility of conducting optical spectroscopy measurements on intact lesions prior to removal during HNSCC procedures, and established that this probe provides diagnostically-relevant physiologic information that may impact further treatment.

Octreotide may improve pharyngocutaneous fistula healing through downregulation of cystatins: A pilot study.

Background: Pharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide. Methods: Four healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration. Results: There were 3076 human, 332 Streptococcus mitis, 102 G. haemolyans, and 42 Granulicatella adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and ~300 proteins that had a p < .05 between the pre- and post-octreotide groups ~50 proteins with an FDR-corrected p < .05 between pre- and post-groups. These results were visualized using a volcano plot after filtering on proteins quantified by 2 more or unique precursors. Both human and bacterial proteins were among the proteins altered by octreotide treatment. Notably, four isoforms of the human cystatins, belonging to a family of cysteine proteases, that had significantly lower abundance after treatment. Conclusion: This pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotide's effects on saliva and reports of improved PCF healing.

Incidence and Risk of Suicide Among Patients With Head and Neck Cancer in Rural, Urban, and Metropolitan Areas.

Importance: Patients with head and neck cancer (HNC) are known to be at increased risk of suicide compared with the general population, but there has been insufficient research on whether this risk differs based on patients' rural, urban, or metropolitan residence status. Objective: To evaluate whether the risk of suicide among patients with HNC differs by rural vs urban or metropolitan residence status. Design, Setting, and Participants: This cross-sectional study uses data from the Surveillance, Epidemiology, and End Results database on patients aged 18 to 74 years who received a diagnosis of HNC from January 1, 2000, to December 31, 2016. Statistical analysis was conducted from November 27, 2020, to June 3, 2021. Exposures: Residence status, assessed using 2013 Rural Urban Continuum Codes. Main Outcomes and Measures: Death due to suicide was assessed by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (U03, X60-X84, and Y87.0) and the cause of death recode (50220). Standardized mortality ratios (SMRs) of suicide, assessing the suicide risk among patients with HNC compared with the general population, were calculated. Suicide risk by residence status was compared using Fine-Gray proportional hazards regression models. Results: Data from 134 510 patients with HNC (101 142 men [75.2%]; mean [SE] age, 57.7 [10.3] years) were analyzed, and 405 suicides were identified. Metropolitan residents composed 86.6% of the sample, urban residents composed 11.7%, and rural residents composed 1.7%. The mortality rate of suicide was 59.2 per 100 000 person-years in metropolitan counties, 64.0 per 100 000 person-years in urban counties, and 126.7 per 100 000 person-years in rural counties. Compared with the general population, the risk of suicide was markedly higher among patients with HNC in metropolitan (SMR, 2.78; 95% CI, 2.49-3.09), urban (SMR, 2.84; 95% CI, 2.13-3.71), and rural (SMR, 5.47; 95% CI, 3.06-9.02) areas. In Fine-Gray competing-risk analyses that adjusted for other covariates, there was no meaningful difference in suicide risk among urban vs metropolitan residents. However, compared with rural residents, residents of urban (subdistribution hazard ratio, 0.52; 95% CI, 0.29-0.94) and metropolitan counties (subdistribution hazard ratio, 0.55; 95% CI, 0.32-0.94) had greatly lower risk of suicide. Conclusions and Relevance: The findings of this cross-sectional study suggest that suicide risk is elevated in general among patients with HNC but is significantly higher for patients residing in rural areas. Effective suicide prevention strategies in the population of patients with HNC need to account for rural health owing to the high risk of suicide among residents with HNC in rural areas.

Head and neck cancer research collaborations between the United States and low- and middle-income countries: 10-year publication analysis.

BACKGROUND: Disparities exist for head and neck cancer (HNC) patients between those in developed countries and low- and middle-income countries (LMICs). To improve HNC care globally, collaborations between the United States and LMICs have been established. Our objectives are: (1) define trends of collaborative HNC publications among LMICs and the United States and (2) assess the global distribution of these publications by region. METHODS: A Scopus search identified all HNC research publications during 2009 to 2018. These were then categorized by type (basic vs. clinical) and by global regions. RESULTS: Five thousand one hundred and seventy collaborative publications were identified, of which 41% were basic science and 59% clinical. The highest rate of collaborative publications for both basic science and clinical papers was seen in the East Asia/Pacific region. CONCLUSIONS: The number of collaborative research publications per year in HNC is increasing across the globe, at varying rates in different global regions.

Surgeon Volume and Complications in Lateral Neck Dissection for Squamous Cell Carcinoma: A Multidatabase Analysis.

OBJECTIVE: To determine whether annual surgeon volume of lateral neck dissections for squamous cell carcinoma is associated with complication rates. STUDY DESIGN: Retrospective review. SETTING: Two US databases spanning 2000 to 2014. METHODS: Neck dissections for squamous cell carcinoma from the National Inpatient Sample and State Inpatient Databases were analyzed. The primary outcome was any in-hospital complication common to neck dissection. The principal independent variable was surgeon volume. A multivariable logistic generalized estimating equation with a piecewise linear spline for surgeon volume was fit to assess its association with complication. RESULTS: The National Inpatient Sample had 3517 discharges fitting criteria, a median surgeon volume of 12, and an 11.1% complication rate. A 1-unit increase in surgeon volume was associated with a 7% increase in the odds of complication when volume ranged between 4 and 19 (adjusted odds ratio [AOR], 1.07; 95% CI, 1.04-1.11) and with a 3% decrease in the odds of complication when volume ranged between 19 and 51 (AOR, 0.97; 95% CI, 0.96-0.99). The State Inpatient Databases had 2876 discharges fitting criteria, a median surgeon volume of 30, and a 13.5% complication rate. Surgeon volume was not associated with complication when <27 (AOR, 1.01; 95% CI, 0.99-1.02), but a 5-unit increase in volume was associated with a 7% decrease in the odds of complication with volume ≥27 (AOR, 0.93; 95% CI, 0.88-0.98). CONCLUSIONS: Surgeon volume was associated with complications for most volume ranges and with lower odds of complication for high-volume surgeons.

Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma.

PURPOSE: In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma. PATIENTS AND METHODS: Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550-4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy. RESULTS: Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%-83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4+ T-cell subsets. CONCLUSIONS: Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.

Comparative Evaluation of Tube First Versus Video Laryngoscope First Techniques in a Normal and Simulated Difficult Airway Model: A Randomized Controlled Trial.

In patients with difficult airways, there can be difficulty with advancing the endotracheal tube into the airway even with a good view of the glottis using video laryngoscopy. The purpose of this study was to determine if the time required to intubate an airway and the number of gaze changes by the laryngoscopist could be decreased by using a novel video laryngoscope technique. Sixteen experienced Certified Registered Nurse Anesthetists were recruited to intubate a manikin with a normal or difficult airway using both the laryngoscope first technique and a new endotracheal tube first technique (4 intubations total) in a randomized sequence. The data were analyzed with the Mann-Whitney (U) test to compare the differences between the normal and difficult airway conditions. Although no significant difference was noted in the time to intubation between intubation techniques, the number of gaze changes was found to be significantly fewer in the tube first technique (P=.0009). A steep learning curve, associated with the accommodation of the manikin, was demonstrated by a decrease in time and gaze changes with subsequent intubations. Incorporating the endotracheal tube first technique into an education curriculum could increase patient safety by decreasing the time to secure a difficult airway.

Plasmonic assay for amplification-free cancer biomarkers detection in clinical tissue samples.

Developing countries have seen a rise in cancer incidence and are projected to harbor three-quarters of all cancer-related mortality by 2030. While disproportionally affected by the burden of cancer, these regions are ill-equipped to handle the diagnostic caseload. The low number of trained pathologists per capita results in delayed diagnosis and treatment, ultimately contributing to increased mortality rates. To address this issue, we developed a point-of-care (POC) plasmonic assay for direct detection of cancer as an alternative to pathological review. Whereas our assay has general applicability in many cancer diagnoses that involve tissue biopsies, we use head and neck cancer (HNC) as a model system because these tumors are increasingly prevalent in lower-income and underserved regions, due to risk factors such as smoking, drinking, and viral infection. Our method uses surface-enhanced Raman scattering (SERS) to detect unique RNA biomarkers from human biopsy samples without the need for complex target amplification machinery (e.g., PCR), making it time and resource-efficient. Unlike previous studies that required target amplification, this work represents a significant advance for HNC diagnosis directly in clinical samples, using only our SERS-based assay for RNA biomarkers. In this study, we tested our assay on 20 clinical samples, demonstrating the accuracy of the method in the diagnosis of head and neck squamous cell carcinoma. We reported sensitivity of 100% and specificity of 97%. Furthermore, we used a handheld Raman device to read the results in order to illustrate the applicability of our method for POC diagnosis of cancer in low-resource settings.

Development of a Surgical Video Atlas for Resident Education: 3-Year Experience.

OBJECTIVE: To create a high-quality annotated online surgical video atlas of key indicator otolaryngology cases and assess its use and overall journal trends over time. METHODS: Videos are recorded from multiple viewpoints within the operating room and compiled into a single stream. Postediting includes chaptering videos and overlaying relevant text annotations. Videos are published online and viewership trends analyzed. RESULTS: Over 3 years, 29 otolaryngology videos were published out of 161 journal publications (18%). Eight of the 14 key indicator procedures are included (57%). From the beginning of 2017 to the end of 2019, viewership of otolaryngology pages increased from 548 to 11,139 views per month, totaling >150,000 views. These now represent 10% of the total journal monthly views and 10% of the overall views. Users originate from the United States and from >10 other countries. DISCUSSION: Residents and faculty face challenges of providing the highest standard of clinical care, teaching, and learning in and out of the operating room. Inherent difficulties of surgical training, high-fidelity surgical simulation, and imposed work hour restrictions necessitate additional, more efficient and effective means of teaching and learning. Surgical videos demonstrating key anatomy, procedural steps, and surgical dexterity with hand positioning are increasing in their popularity among learners. IMPLICATIONS FOR PRACTICE: Surgical video atlases provide a unique adjunct for resident education. They are enduring and easily accessible. In a climate of work hour restrictions or elective case reduction, they may supplement how residents learn to operate outside the operating theater.

The effect of lateral neck dissection on complication rate for total thyroidectomy.

PURPOSE: To determine the complication profile for total thyroidectomy with and without concomitant lateral neck dissection using a large administrative database. MATERIALS AND METHODS: The IBM MarketScan® Commercial Database (2010-2014) analytic cohort was queried for patients ≥18 years or older undergoing total thyroidectomy (or equivalent procedures) from January 1, 2010 to June 30, 2014. Subgroup analysis was performed for patients undergoing concomitant unilateral and bilateral lateral neck dissection. The complication profiles were described. RESULTS: 55,204 patients underwent total thyroidectomy or equivalent procedures. Hypoparathyroidism or hypocalcemia was coded in 20.3% overall, with 4.7% having permanent hypoparathyroidism. Vocal cord paralysis was coded in 3.3% overall with permanent rate of 0.7%. Tracheotomy was performed in 0.3% of patients. 2743 underwent total thyroidectomy with concomitant unilateral lateral neck dissection, and 560 of these patients underwent bilateral lateral neck dissection. In patients undergoing unilateral lateral neck dissection, 30.5% of patients have hypoparathyroidism/hypocalcemia coded, with a permanent rate of 8.8%. Vocal cord paralysis was coded in 8.3% of patients, with a permanent rate of 1.9%. Tracheotomy was performed in 1.2% of patients. In patients undergoing bilateral lateral neck dissection, 39.6% had hypoparathyroidism/hypocalcemia coded, with a permanent rate of 10.9%. These patients had vocal cord paralysis coded in 10.2% of cases, with a permanent rate of 2.1%. Tracheotomy was performed in 2.5% of patients. CONCLUSION: The addition of unilateral and especially bilateral lateral neck dissection increases both overall and permanent complication rates for total thyroidectomy. These data may help to inform preoperative discussions with patients.

Idiopathic Sudden Sensorineural Hearing Loss Is Not a Sentinel Event for Acute Myocardial Infarction.

OBJECTIVE: Given ongoing debate about the suggested association, the primary objective was to determine if idiopathic sudden sensorineural hearing loss (ISSNHL) was a sentinel event for acute myocardial infarction (AMI) in adults. STUDY DESIGN: Case-control study. SETTING: United States MarketScan administrative health claims database. PATIENTS: Aged 18 years or older, had a diagnosis of ISSNHL on or after January 1st, 2011 and had sufficient follow-up data available to assess for AMI occurrence. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Incidence rates (per 1,000 patient years) of AMI for cases and controls were computed. Adjusted and unadjusted Cox proportional hazards models were created to explore possible associations between ISSNHL and initial AMI. RESULTS: A total of 10,749 ISSNHL cases and 10,749 matched controls were included. There were no significant differences in the incidence rate of AMI between ISSNHL cases (8.29 events/1,000 person-years) and controls (9.25 events/1,000 person-years), nor were there differences within age groups, sex, or comorbidity status (overall incidence rate ratio 0.90; 95% confidence interval [CI] 0.70-1.15 p = 0.39). The unadjusted and adjusted Cox proportional hazards models did not demonstrate an association between ISSNHL and initial AMI (hazard ratio [HR]: 0.90, 95% CI: 0.70-1.15; HR: 0.86, 95% CI: 0.67-1.10, respectively). CONCLUSIONS: ISSNHL is not a predictor of an initial AMI in adult patients from the United States. Considerable inconsistencies in associations between cardiovascular risk factors and ISSNHL exist in the literature. Further work is needed to confirm or refute direct associations between cardiovascular disease risk factors and ISSNHL before definitive mechanistic conclusions can be made.

Assessing effects of pressure on tumor and normal tissue physiology using an automated self-calibrated, pressure-sensing probe for diffuse reflectance spectroscopy.

Diffuse reflectance spectroscopy (DRS) represents a quantitative, noninvasive, nondestructive means of assessing vascular oxygenation, vascularity, and structural properties. However, it is known that such measurements can be influenced by the effects of pressure, which is a major concern for reproducible and operator-independent assessment of tissues. Second, regular calibration is a necessary component of quantitative DRS to account for factors such as lamp decay and fiber bending. Without a means of reliably controlling for these factors, the accuracy of any such assessments will be reduced, and potentially biased. To address these issues, a self-calibrating, pressure-controlled DRS system is described and applied to both a patient-derived xenograft glioma model, as well as a set of healthy volunteers for assessments of oral mucosal tissues. It was shown that pressure had a significant effect on the derived optical parameters, and that the effects on the optical parameters were magnified with increasing time and pressure levels. These findings indicate that not only is it critical to integrate a pressure sensor into a DRS device, but that it is also important to do so in an automated way to trigger a measurement as soon as possible after probe contact is made to minimize the perturbation to the tissue site.