De novo mapping of α-helix recognition sites on protein surfaces using unbiased libraries.

The α-helix is one of the most common protein surface recognition motifs found in nature, and its unique amide-cloaking properties also enable α-helical polypeptide motifs to exist in membranes. Together, these properties have inspired the development of α-helically constrained (Helicon) therapeutics that can enter cells and bind targets that have been considered "undruggable", such as protein-protein interactions. To date, no general method for discovering α-helical binders to proteins has been reported, limiting Helicon drug discovery to only those proteins with previously characterized α-helix recognition sites, and restricting the starting chemical matter to those known α-helical binders. Here, we report a general and rapid screening method to empirically map the α-helix binding sites on a broad range of target proteins in parallel using large, unbiased Helicon phage display libraries and next-generation sequencing. We apply this method to screen six structurally diverse protein domains, only one of which had been previously reported to bind isolated α-helical peptides, discovering 20 families that collectively comprise several hundred individual Helicons. Analysis of 14 X-ray cocrystal structures reveals at least nine distinct α-helix recognition sites across these six proteins, and biochemical and biophysical studies show that these Helicons can block protein-protein interactions, inhibit enzymatic activity, induce conformational rearrangements, and cause protein dimerization. We anticipate that this method will prove broadly useful for the study of protein recognition and for the development of both biochemical tools and therapeutics for traditionally challenging protein targets.

Evaluation of stapes mobilization in the 21st century for conductive hearing loss in the otosclerotic ear.

PURPOSE: Compare outcomes of stapes mobilization and stapedectomy performed by a single surgeon for the otosclerosis. MATERIALS AND METHODS: A retrospective chart review of adult patients who underwent stapes mobilization or stapedectomy for otosclerosis was performed. Operative notes reviewed; patients included if diagnosed with otosclerosis without another otologic disease that could contribute to their hearing loss and all required data were available. Pre-and post-operative audiograms at 1, 6, and 12-months were evaluated to compare the air-bone gaps between the mobilization and stapedectomy procedures. The rates of sensorineural hearing loss also were compared. Student t-tests and multiple regression models were used to ascertain the association between improvement in post-operative air-bone gaps, sensorineural hearing loss, and the procedure undertaken. RESULTS: Sixty-seven (n = 67) patients with 108 procedures were included for analysis. No substantial difference between the surgical subgroups was found when comparing stapes mobilization to stapedectomy, and there was no evidence to suggest that either surgical procedure was superior to the other based on the data obtained and analyzed. Improvements in air-bone gap averaged 15.79 dB for stapes mobilization and 19.23 dB for stapedectomy. The results of the study showed no evidence of post-operative sensorineural hearing loss or change in air-bone gaps when comparing virgin to "revision" stapedectomy largely in patients who had failed previous mobilization. CONCLUSION: Stapes mobilization provides a conservative approach to otosclerosis patients suffering from conductive hearing loss. Stapedectomy can be used to correct failed mobilization.

Golf-Related Craniofacial Injuries in Adults: A NEISS Database Study.

INTRODUCTION: Despite its popularity, there have been no reports outlining adult craniofacial trauma in the setting of golf injuries. Our main objective was to identify and describe trends in head and neck injuries incurred while participating in golf including injury type, anatomic location, and patient disposition. METHODS: A retrospective cohort analysis of the National Electronic Injury Surveillance System (NEISS) was conducted from 2009-2018. Population characteristics of golf-related injuries were recorded, including, age, sex, and race distributions. Distribution of injury anatomic location, injury type, distribution of fracture location, patient disposition was further analyzed. A one way ANOVA was utilized to obtain the mean ages for all injuries and compare them for any statistical difference. To identify statistical significance, a Fisher exact test with a Monte Carlo simulation was performed. RESULTS: A total of 509 golf-related injuries (national estimate 24,425 cases) were recorded over the study period. Lacerations were the most common injury overall (54.2%), while contusions and abrasions were the next most common injuries (27.3%). The most common fracture subtype observed was midface (40.43%), followed by nasal bone (27.66%), mandible (12.77%), skull (12.77%), and cervical spine (6.38%). The highest proportion of patients admitted for further treatment were individuals >70 years of age. Fractures had the highest rate of admission (29.8%). CONCLUSIONS: A better understanding of golf injuries can allow for rapid detection and appropriate treatment when encountered. This knowledge can also help to develop safety precautions by potentially reforming rules and regulations as well as protective equipment.

Clinical predictors of immediate intervention for isolated renal trauma.

INTRODUCTION Evidence suggests overutilization of procedural intervention for renal traumas. The objective of this study was to assess clinical factors associated with procedural intervention for patients presenting to the emergency department (ED) with isolated renal trauma. MATERIALS AND METHODS: A United States statewide trauma registry was queried for trauma patients presenting to level I or II trauma centers with isolated renal injuries (Grades I-V) from 2000-2013. Patient demographics, mechanism, American Association for the Surgery of Trauma (AAST) grade, trauma center level designation, presenting ED vital signs, Glasgow Coma Scale (GCS), intubation status, and blood product transfusion were assessed. RESULTS: Of 449,422 patients, 1383 patients (78% male, median age 29 years [range 2-92]) with isolated renal injuries had data available for analysis. Controlling for demographics, presenting vitals, GCS, trauma center level, mechanism and intubation status, level I status (OR 2.1 [1.3-3.4], p = 0.0021), white race (OR 2.5 [1.3-4.7], p < 0.005), AAST IV/V injury (OR 4.79 [3.1-6.5], p < 0.0001) and blood product administration (OR 2.7 [1.5-4.9], p = 0.0009) were independently associated with an immediate interventional radiology procedure. Independent predictors of immediate surgical intervention include level I status (OR 2.2 [1.2-4.0], p = 0.0075), penetrating mechanism of injury (OR 15.6 [8.4-28.9], p < 0.0001, AAST IV/V injury (OR 13.6 [8.7-21.1], p < 0.0001), and clinical hypotension (SBP < 95 mmHg, OR 2.1 [1.1 4.2], p = 0.03). CONCVLUSION: Level 1 trauma center designation, white race, penetrating mechanism of injury, high-grade injury, transfusion of blood products, and hypotension were all independent predictors of immediate procedural intervention following ED presentation with isolated renal trauma.

Bridging gaps in heart valve disease care: Opportunities for quality improvement.

In January 2018, the Society of Cardiovascular and Angiography Interventions (SCAI) and Avalere Health ("Avalere") launched the development of the Heart Valve Initiative to advance the identification and management of patients with heart valve disease. To define the priority gap areas in identification and management of valve disease, a formal environmental scan was conducted to uncover current and planned initiatives that might inform the development of the initiative and bring to light stakeholder activities that seek to address the target patient population. This document summarizes the methodology and key findings from the scan, which will inform the development of interventions, research questions, and quality measure concepts to consider. Understanding that quality improvement initiatives and evidence in cardiovascular care may evolve rapidly, this synopsis represents a snapshot of information gathered from February 2018 to May 2019.

Cell-cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis.

Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and little is known about how multicellular signal processing modulates single-cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored whether cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow epidermal growth factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells.

Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in Gap Junction Channels Composed of Connexin32.

Tryptophan was substituted for residues in all four transmembrane domains of connexin32. Function was assayed using dual cell two-electrode voltage clamp after expression in Xenopus oocytes. Tryptophan substitution was poorly tolerated in all domains, with the greatest impact in TM1 and TM4. For instance, in TM1, 15 substitutions were made, six abolished coupling and five others significantly reduced function. Only TM2 and TM3 included a distinct helical face that lacked sensitivity to tryptophan substitution. Results were visualized on a comparative model of Cx32 hemichannel. In this model, a region midway through the membrane appears highly sensitive to tryptophan substitution and includes residues Arg-32, Ile-33, Met-34, and Val-35. In the modeled channel, pore-facing regions of TM1 and TM2 were highly sensitive to tryptophan substitution, whereas the lipid-facing regions of TM3 and TM4 were variably tolerant. Residues facing a putative intracellular water pocket (the IC pocket) were also highly sensitive to tryptophan substitution. Although future studies will be required to separate trafficking-defective mutants from those that alter channel function, a subset of interactions important for voltage gating was identified. Interactions important for voltage gating occurred mainly in the mid-region of the channel and focused on TM1. To determine whether results could be extrapolated to other connexins, TM1 of Cx43 was scanned revealing similar but not identical sensitivity to TM1 of Cx32.

The Actual Role of Receptors as Cancer Markers, Biochemical and Clinical Aspects: Receptors in Breast Cancer.

A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. The discovery and development of proper biomarkers is a critical part of modern oncology. Among the many different types of biomarkers, cell receptors have demonstrated important roles as diagnostic, prognostic, and predictive biomarkers in cancer research and therapy, leading to their integration into drug development trials. In breast cancer, Estrogen/Progesterone receptors and HER2/neu receptors are two good examples of biomarkers that are prognostic of outcomes, as well as predictive of response to certain therapies. Limitations exist, however, such as the invasive procedures required obtaining tissue, and the difficulty measuring the actual distribution of the receptors. Thus, continued efforts to develop receptors as comprehensive cancer biomarkers with novel approaches is mandated to further advance the modern oncology.

Physician communication in the operating room.

In this study, communication research was conducted with multidisciplinary groups of operating-room physicians. Theoretical frameworks from intercultural communication and rhetoric were used to (a) measure latent cultural communication variables and (b) conduct communication training with the physicians. A six-step protocol guided the research with teams of physicians from different surgical specialties: anesthesiologists, general surgeons, and obstetrician-gynecologists (n = 85). Latent cultural communication variables were measured by surveys administered to physicians before and after completion of the protocol. The centerpiece of the 2-hour research protocol was an instructional session that informed the surgical physicians about rhetorical choices that support participatory communication. Post-training results demonstrated scores increased on communication variables that contribute to collaborative communication and teamwork among the physicians. This study expands health communication research through application of combined intercultural and rhetorical frameworks, and establishes new ways communication theory can contribute to medical education.

Brief report: citrullination within the atherosclerotic plaque: a potential target for the anti-citrullinated protein antibody response in rheumatoid arthritis.

OBJECTIVE: To investigate whether citrullinated proteins within the atherosclerotic plaque can be targeted by anti-citrullinated protein antibodies (ACPAs), forming stimulatory immune complexes that propagate the progression of atherosclerosis. METHODS: Protein lysates prepared from atherosclerotic segments of human aorta were assessed for the presence of citrulline-modified proteins, and specifically citrullinated fibrinogen (Cit-fibrinogen), by immunoprecipitation and/or immunoblotting followed by mass spectrometry. Immunohistochemical analysis of coronary artery plaque was performed to determine the presence of citrullinated proteins and peptidylarginine deiminase type 4 (PAD-4). Serum levels of anti-cyclic citrullinated peptide (anti-CCP), anti-citrullinated vimentin (anti-Cit-vimentin), and anti-Cit-fibrinogen antibodies were measured in 134 women with seropositive rheumatoid arthritis; these subjects had previously been characterized for the presence of subclinical atherosclerosis, by electron beam computed tomography scanning. RESULTS: Western blot analysis of atherosclerotic plaque lysates demonstrated several citrullinated proteins, and the presence of Cit-fibrinogen was confirmed by immunoprecipitation and mass spectrometry. Immunohistochemical analysis showed colocalization of citrullinated proteins and PAD-4 within the coronary artery plaque. In age-adjusted regression models, antibodies targeting Cit-fibrinogen and Cit-vimentin, but not CCP-2, were associated with an increased aortic plaque burden. CONCLUSION: Citrullinated proteins are prevalent within atherosclerotic plaques, and certain ACPAs are associated with the atherosclerotic burden. These observations suggest that targeting of citrullinated epitopes, specifically Cit-fibrinogen, within atherosclerotic plaques could provide a mechanism for the accelerated atherosclerosis observed in patients with RA.

Phase comparison and equation of state for Ta2O5.

Tantalum pentoxide (Ta2O5) is among the most technologically useful heavy transition metal oxides. Unfortunately, its crystal structure is the subject of long-standing and unresolved disagreement. Among other consequences, this uncertainty has made it impossible to formulate a robust high pressure equation of state for Ta2O5. Here, we report the results of high pressure x-ray diffraction experiments indexed against a comprehensive list of proposed Ta2O5phases. Five of the proposed phases produce good matches to experimental observations, and the compressibility parameters for these phases are all consistent within uncertainty. This means that regardless of the particular phase chosen, the Ta2O5equation of state can be described with bulk modulusK0=138±3.68 GPa and pressure derivativeK0'=1.82±0.45. Combining these experimental results with new density-functional theory calculations allows us to identify theλphase as the best structural model of Ta2O5at ambient conditions.

A 16-Year Chronicle of Developing a Healthy Workplace Participatory Program for Total Worker Health® in the Connecticut Department of Correction: The Health Improvement through Employee Control (HITEC) Program.

Health Improvement Through Employee Control (HITEC) is a 16-year program directed toward the health of corrections personnel and developed through the application of the principles of Participatory Action Research (PAR) and participatory ergonomics. Its impetus has always been the adverse health status of the corrections workforce: early mortality, depression, obesity, and hypertension. The HITEC program trained small "Design Teams" (DTs) of front-line personnel in participatory methods for intervention design for health improvement and organizational change in line with the Total Worker Health® principles. Periodic surveys and physical testing were introduced for longitudinal assessments. Comparative interventions at comparable sites included DTs without a priori assignation, problem-focused kaizen effectiveness teams (KETs), and bargaining unit-centered DTs. DT resilience and the replacement of members who transferred facilities or retired was aided by novel cooperative administrative structures. DT-generated interventions included stress lounges, changes in critical event report writing, a joint program with trained inmates to improve air quality, and training in staff mental health and sleep behavior. A specialized peer-to-peer Health Mentoring Program (HMP) paired new officers with trained peers. Many interventions and program features were institutionalized, thus improving prospects for self-supporting program longevity. Participatory interventions designed and supported by the corrections workforce were found to be both feasible and exceptionally effective.

Spontaneous coronary artery dissection: A review of medical management approaches.

Spontaneous coronary artery dissection (SCAD) is an underdiagnosed cause of acute coronary syndrome (ACS) that usually presents in young female patients. Risk factors include female sex, physical and emotional stressors, and fibromuscular dysplasia, and diagnosis is usually made by coronary angiography aided by intravascular ultrasound (IVUS) or optical coherence tomography (OCT). While conservative treatment is usually preferred over percutaneous coronary intervention or surgery, medical management of SCAD has been under debate. This comprehensive review aims to summarize findings from recent studies exploring various medical treatment approaches for the management of SCAD. Antiplatelet therapy with aspirin is generally safe and beneficial for SCAD patients, with dual antiplatelet (DAPT) being recommended for patients undergoing PCI. In the absence of intervention, DAPT may be given for a short period followed by a longer single-antiplatelet (SAPT) therapy with aspirin. Beta-blockers appear to be safe and effective for SCAD patients. On the other hand, fibrinolytics, anticoagulants, and glycoprotein IIa/IIIb inhibitors are contraindicated. Cardiovascular medications such as renin-angiotensin-aldosterone system (RAAS) inhibitors, mineralocorticoid receptor antagonists, and statins are not recommended in the absence of left ventricular dysfunction. Hormonal therapy is contraindicated for patients who develop SCAD during pregnancy and future pregnancy is discouraged in that patient population.

Glans hypermobility scale (GHS): A simple grading scale and description of a modified glanspexy technique.

Glans hypermobility (GH) is a well-described clinical entity that can have significant implications for cosmesis and function, resulting in sexual dissatisfaction, penile pain, and early device erosion, with an estimated incidence of 0.04% to 10%. We developed a novel grading scale to assess GH severity intraoperatively during primary inflatable penile prosthesis (IPP) placement and describe a modified glanspexy technique to correct GH when encountered during IPP placement. 530 patients who underwent primary IPP placements from two high-volume prosthetic surgeons between February 2018 - November 2019 were retrospectively reviewed in order to identify the incidence of GH. Of these, 139 (26.2%) had hypermobility. Employing our new scaling system, grade 1, 2, and 3 GH was seen in 86 (16.2%), 29 (5.5%), and 24 (4.5%) cases, respectively. Increased implant size correlated with a decreased likelihood of GH incidence. Each increase in implant size by 1 cm decreased the incidence of detecting GH by 11.0% (OR = 0.89; p = 0.015). 11 patients underwent primary GH repair using our described technique. At one-year follow-up, one patient required repeat glanspexy for recurrent bothersome GH and a second patient developed a suture granuloma at the glanspexy incision requiring unilateral cylinder explant. Our modified glanspexy technique can be used to correct GH in any direction and is a useful tool for the prosthetic surgeon's armamentarium.

Does Tighter Glycemic Control Beyond Hemoglobin A1c of 8% Improve Outcome for Lumbar Spine Surgery? A MSSIC Study.

BACKGROUND AND OBJECTIVES: Diabetes mellitus is associated with increased risk of postoperative adverse outcomes. Previous studies have emphasized the role of glycemic control in postoperative complications. This study aims to ascertain whether controlling hemoglobin A1c (HbA1c) lower than 8% preoperatively results in meaningful risk reduction or improved outcomes. METHODS: We used patient-level data from the Michigan Spine Surgery Improvement Collaborative registry, focusing on patients who underwent elective lumbar spine surgery between 2018 and 2021. The primary outcomes were length of stay and the occurrence of postoperative adverse events. Secondary outcomes included patient satisfaction, achievement of a minimum clinically important difference (MCID) of Patient-Reported Outcomes Measurement Information System-Physical Function, the EuroQol-5D and NRS of leg and back pain, and return to work. RESULTS: A total of 11 348 patients were included in this analysis. Patients with HbA1c above the thresholds before surgery had significantly higher risks of urinary retention for all 3 possible threshold values (incidence rate ratio [IRR] = 1.30, P = .015; IRR = 1.35, P = .001; IRR = 1.25, P = .011 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively). They also had longer hospital stay (IRR = 1.04, P = .002; IRR = 1.03, P = .001; IRR = 1.03, P < .001 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively) and had higher risks of developing any complication with HbA1c cutoff of 7.5% (IRR = 1.09, P = .010) and 7% (IRR = 1.12, P = .001). Diabetics with preoperative HbA1c above all 3 thresholds were less likely to achieve Patient-Reported Outcomes Measurement Information System MCID at the 90-day follow-up (IRR = .81, P < .001; IRR = .86, P < .001; IRR = .90, P = .007 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively) and less likely to achieve EuroQol-5D MCID at the 2-year follow-up (IRR = .87, P = .027; IRR = .84, P = .005 for the HbA1c cutoffs of 7.5% and 7%, respectively). CONCLUSION: Our study suggests that reducing HbA1c below 8% may have diminishing returns regarding reducing complications after spine surgery.

Modeling intercellular transfer of biomolecules through tunneling nanotubes.

Tunneling nanotubes (TNTs) have previosly been observed as long and thin transient structures forming between cells and intercellular protein transfer through them has been experimentally verified. It is hypothesized that this may be a physiologically important means of cell-cell communication. This paper attempts to give a simple model for the rates of transfer of molecules across these TNTs at different distances. We describe the transfer of both cytosolic and membrane bound molecules between neighboring populations of cells and argue how the lifetime of the TNT, the diffusion rate, distance between cells, and the size of the molecules may affect their transfer. The model described makes certain predictions and opens a number of questions to be explored experimentally.

Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling.

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.

Does the Severity of Vocal Fold Paresis on Laryngeal Electromyography Correlate With Radiographic Findings on Cross Sectional Imaging?

OBJECTIVES: Unilateral vocal fold paresis or paralysis (UVFP) is a condition for which radiographic evaluation and laryngeal electromyography (LEMG) are valuable to evaluate severity of injury and direct treatment plans. Despite extensive research involving findings suggestive of UVFP with radiographic imaging, no study has attempted to determine which findings suggestive of UVFP on imaging are clinically significant and suggest a need for intervention. The purpose of this study was to evaluate whether the severity of vocal fold paresis/paralysis affects the likelihood of encountering radiographic findings suggestive of UVFP. We also aimed to determine which findings suggestive of UVFP on imaging were clinically significant and were associated with surgical intervention. MATERIALS AND METHODS: A retrospective chart review was conducted of patients who had been diagnosed with unilateral vocal fold paresis or paralysis and had been evaluated by CT scan and/or magnetic resonance imaging and laryngeal electromyography (EMG) between the dates of January 1, 2017 and January 9, 2018. Fisher's exact testing with Monte Carlo Simulation was utilized to determine statistical significance of identified relationships. Univariate analysis was conducted to assess for individual relationships between imaging results and the potential predictor variables. Chi square analysis was conducted with the various categorical variables to assess for any potential relationships to imaging results. Statistical significance was determined utilizing chi square analysis. RESULTS: After data collection, 130 patients were included in the study population. Of the 112 patients with documented MRI results, 17% had a reported imaging abnormality suggestive of true vocal fold paresis or paralysis (VFP). Of the 71 patients with documented CT Neck results, 15.4% had an abnormality potentially concerning for true VFP. The average decrease in recruitment of the right and left SLN was 23.8% and 26.1%, respectively. The average decrease in recruitment of the right and left RLN was 37.3% and 57.78%, respectively. Seventy four percent of patients who exhibited abnormal MRI were found to have isolated SLN weakness, and 21% of patients were found to have a combined SLN and ipsilateral RLN weakness. In patients with abnormal CT scans 45% were found to have isolated SLN weakness, and 35% were found to have a combined SLN and RLN weakness. MRI imaging again failed to display any significant degree of paresis. However, abnormal CT results displayed severe CN X paresis in 36.84% vs 1.96% in normal scans. The chance of an abnormal MRI and CT result was 2.78 and 5.55 times greater, respectively, for each increase in the degree of severity of CN X paresis. When looking at the ability of imaging to predict the chance of a patient undergoing surgery, 34.8% of patients with an abnormal MRI underwent surgery compared to just 14.61% of those with normal scans. For CT scans, 35% of patients with an abnormal scan underwent surgery, compared with only 15.69% with normal imaging. When pooled, over 33% of patients with any abnormal imaging underwent a laryngeal procedure compared to 13% of patients with normal imaging. CONCLUSIONS: There is a relationship between severity of vocal fold paresis found on laryngeal EMG and likelihood of detection on imaging. While CT was more likely to find characteristics of UVFP than MRI, patients who had an abnormal finding on either modality were more likely to undergo surgical intervention. These findings highlight the importance of early referral of patients with abnormal laryngeal imaging to an otolaryngologist for evaluation and possible intervention.

Surgical Outcome of Potassium-Titanyl-Phosphate (KTP) Laser Photocoagulation for Vocal Fold Vascular Lesions.

INTRODUCTION: Laser technology is used in microscopic direct laryngeal surgery for a variety of indications. Lasers are categorized broadly as photoangiolytic or cutting/ablating lasers, based on the chromophores that absorb their energy. Photoangiolytic lasers such as the 532 nm Potassium-Titanyl-Phosphate (KTP) laser are absorbed selectively by the chromophore hemoglobin, facilitating controlled intravascular coagulation, with preservation of the overlying epithelium and adjacent tissue. Efficacy of the KTP laser has been demonstrated for incision, coagulation, and ablation in vocal fold (VF) surgery. OBJECTIVE: The purpose of the present study was to examine surgical outcomes following KTP laser photocoagulation for the management of VF vascular lesions. METHODS: Adult patients with sufficient data who had undergone KTP laser photocoagulation in the operating room for the treatment of VF vascular lesions were included in this retrospective study. Strobovideolaryngoscopy (SVL) video footage from all preoperative visits and all available postoperative visits was compiled and de-identified. Patients were followed up at days 1-7, 8-14, 30-60, and greater than 60 days after surgery. Three blinded physician evaluators reviewed and evaluated the SVL footage independently for postoperative outcome parameters. Postoperative SVL video footage was evaluated on a 5-point scale for surgical success (surgical objective score; 1 = failure and 5 = complete success). The average surgical objective score was 4.36, 4.04, 4.25, and 4.46 (out of 5) at postoperative visits 1-4, respectively. RESULTS: There were 60 cases (19 male and 41 female) included in the retrospective cohort. The average age was 42.42 ± 15.51 (range = 18-74). Fifty-one-point six seven percent of subjects were professional voice users (singers, teachers, public speakers, and others). All subjects were diagnosed preoperatively with VF vascular malformations and had undergone pulsed KTP laser photocoagulation. There were 40 bilateral cases and 20 unilateral cases, for a total of 100 VFs included in the study. Vascular malformation recurrence was identified in 3.00% and 10.00% of subjects at the third and fourth postoperative visits, retrospectively. The formation of new vascular malformations was identified in 0.00%, 1.00%, 6.00%, and 7.00% of subjects at postoperative visits 1-4, respectively. CONCLUSION: KTP laser photocoagulation is highly effective for the management of vocal fold vascular lesions. Presence of hemorrhage or edema does not affect the long-term surgical outcome. In relatively few cases, vascular lesion recurrence or formation of new vascular lesions may occur.

Gluten Sensitivity Underlying Resistant "Laryngopharyngeal Reflux" Symptoms and Signs.

INTRODUCTION: Laryngopharyngeal reflux (LPR) is one of the most common conditions encountered in otolaryngology. Gluten sensitivity may mimic the signs and symptoms of LPR or act as an aggravating cofactor with LPR. Gluten sensitivity and food intolerance also have been implicated as conditions that may be associated specifically with LPR symptoms and signs resistant to traditional medical treatment. Medical management of LPR may be insufficient to control symptoms and laryngeal signs of reflux, constituting resistant LPR. Eliminating gluten from the diet could provide symptomatic relief to patients with gluten sensitivity and LPR that is not controlled adequately by current regimens. The purpose of our study was to investigate the relationship between gluten sensitivity and LPR. We aimed to evaluate reflux finding score (RFS) improvement following elimination of gluten from the diet in patients with resistant LPR who had positive blood tests associated with gluten sensitivity. Symptom improvement was also assessed following dietary gluten elimination. Lastly, we aimed to identify predictors for a positive response to a gluten-free diet. METHODS: Adult patients who underwent gluten sensitivity testing for treatment-resistant LPR symptoms and/or signs were included. Patients with ≥1 positive test were advised to begin a therapeutic trial of a gluten-free diet. Subjects who chose not to trial a gluten-free diet or tested negative for gluten sensitivity markers served as controls. RFS was the primary outcome measure. RESULTS: One hundred ninety-seven patients were included; 81 trialed a gluten-free diet. Subjects who trialed the gluten-free diet were significantly more likely to demonstrate objective improvement in RFS (77.14% vs 43.88%), and report subjective improvement (55.41% vs 25.77%) than those who did not. RFS had decreased significantly from baseline at 1-3, 3-6, 6-12, and >12-month interval follow-up examinations in subjects who trialed a gluten-free diet. Comparison between subjects who trialed the gluten-free diet, tested positive for a gluten sensitivity marker but did not trial the gluten-free diet, and subjects who were negative for all gluten sensitivity markers revealed that a gluten-free diet was associated with a significantly greater percent improvement in RFS compared to controls at 1-3, 6-12, and >12-months. CONCLUSION: Gluten sensitivity can mimic or aggravate LPR. A gluten-free diet should be considered for patients with resistant LPR, especially if blood test abnormalities that suggest gluten sensitivity are identified. The diet should be maintained for a minimum of three months to demonstrate objective improvement using RFS.