Difference in Perception of Nasal Aesthetic Appearance Between Surgeons and Rhinoplasty Patients: A Single-Center Perspective.

BACKGROUND: Patient satisfaction is an essential outcome measure after a rhinoplasty. Yet it is not known whether the opinions of rhinoplasty patients and surgeons on nasal aesthetic appearance differ. OBJECTIVES: The aim of this study was to determine the differences between patients and surgeons in their perception of nasal aesthetic appearance. METHODS: A retrospective cohort of 300 patients seen in consultation for cosmetic, functional, or combined cosmetic and functional rhinoplasty at a single tertiary care center from June 2017 to June 2020 was studied. Based on preoperative patient images, 6 surgeons with varying levels of expertise assessed nasal aesthetics utilizing a modified Standardized Cosmesis and Health Nasal Outcomes Survey for nasal cosmesis (SCHNOS-C). These scores were then compared to the patient-reported SCHNOS-C scores. RESULTS: The cosmetic, functional, and combined subgroups consisted of 100 patients each. The mean [standard deviation] age was 35.4 [13.7] years and 64% were women. The modified SCHNOS-C scores were well-correlated among the 6 surgeons but showed only weak correlations of 0.07 to 0.20 between patient-reported scores and scores assessed by the surgeons. Compared with the surgeon's scores, patients in the cosmetic subgroup perceived their nasal aesthetic problems to be more severe whereas the those in the functional subgroup perceived their nasal aesthetic problems to be milder compared with the surgeons' assessment. CONCLUSIONS: Our findings suggest that patients and surgeons perceive nasal cosmesis differently. This difference should be considered carefully when planning rhinoplasty or assessing its outcome.

Photography and Photodocumentation for the Rhinoplasty Patient.

Photodocumentation is an essential part of a rhinoplasty surgeon's practice. Preoperative photographs are an indispensable device for patient counseling and surgical planning. Comparison of preoperative and postoperative photographs allow for outcome evaluation, which has a variety of applications-clinical, research, teaching, medicolegal. The ever-evolving technology of photography may seem daunting, but developing a basic understanding of this tool is imperative for a successful rhinoplasty practice. This article reviews the basic photographic principles, equipment, and techniques that are essential to produce high-quality and standardized patient photographs.

A Randomized Single-Blinded Trial of Ibuprofen- versus Opioid-Based Primary Analgesic Therapy in Outpatient Otolaryngology Surgery.

OBJECTIVE: To compare the efficacy of pain control and opioid consumption between patients who receive opioid as primary analgesic therapy and those who receive ibuprofen. STUDY DESIGN: Prospective randomized trial. SETTING: Tertiary care academic hospital. SUBJECT AND METHODS: Adult patients undergoing outpatient otolaryngology surgery were assigned to take hydrocodone/acetaminophen or ibuprofen for postoperative analgesia. Patient-recorded pain scores and analgesic consumption were analyzed. RESULTS: Out of 185 recruits, 108 (58%) completed responses. Fifty-six patients (52%) received opioid medication for primary analgesic treatment versus 52 (48%) who received ibuprofen. There was no difference in reported pain scores between the treatment groups. Those who received ibuprofen as primary therapy reported a significantly lower consumption of opioid medication at 2.04 tablets/pills (95% CI, 0.9-3.1) versus 4.86 (3.6-6.1; P = .001). Based on multivariate analysis, male sex and older age exhibited lower reported pain scores, while older age and use of ibuprofen as primary therapy exhibited lower opioid requirements. CONCLUSION: For postoperative pain management in outpatient otolaryngology procedures, ibuprofen as primary therapy can provide equally effective pain control as compared with hydrocodone/acetaminophen while decreasing overall opioid requirement. Prescription pill counts are further described to help guide physician practices in the era of an opioid epidemic.

Mandibular muscle attachments in genial advancement surgery for obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: Genioglossus advancement is performed in select patients with obstructive sleep apnea. Surgical techniques attempt to capture the genial tubercle of the mandible; however, measurements of the genioglossus, geniohyoid, and digastric muscles are poorly delineated. This investigation is the largest anatomic study exploring the muscles of genial advancement surgery and the first to quantitatively characterize muscular attachments relative to the tubercle, providing new insights from an anatomic perspective on optimizing muscular advancement. STUDY DESIGN: Cadaveric study. METHODS: Fifty-three fresh cadaveric mandibles underwent dissection of the genial tubercle and genioglossus, geniohyoid, and digastric muscles. RESULTS: Genial tubercle, geniohyoid, and genioglossus mean height was 7.78 mm, 5.15 mm, and 6.11 mm, respectively. On average, the geniohyoid began 4.88 mm and ended 10.03 mm from the inferior border of the mandible; the genioglossus 11.91 mm and 18.01 mm, similarly. Intermuscular distance, if present, was 2.67 mm; the muscles overlapped in 28% of cadavers. The combined vertical height of the muscles at their mandibular attachment was 13.94 mm, significantly differing from the height of the genial tubercle. The left and right lateral insertion of the digastric muscles was 19.34 mm and 19.31 mm, respectively, from midline. CONCLUSIONS: The variable range of muscle attachments suggests that genioglossal and geniohyoid attachments extend beyond the genial tubercle and may not originate concentrically from the tubercle, but overlap and lie in very close proximity. Mandibular anterior muscle attachments require anatomic accuracy and an effective operative evaluation of advancement before reproducible, clinically effective osteotomies can be recommended. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2424-2429, 2019.

Esophagram findings in cervical esophageal stenosis: A case-controlled quantitative analysis.

OBJECTIVE: Cervical esophageal stenosis is often diagnosed with a qualitative evaluation of a barium esophagram. Although the esophagram is frequently the initial screening exam for dysphagia, a clear objective standard for stenosis has not been defined. In this study, we measured esophagram diameters in order to establish a quantitative standard for defining cervical esophageal stenosis that requires surgical intervention. STUDY DESIGN: Single institution case-control study. METHODS: Patients with clinically significant cervical esophageal stenosis defined by moderate symptoms of dysphagia (Functional Outcome Swallowing Scale > 2 and Functional Oral Intake Scale < 6) persisting for 6 months and responding to dilation treatment were matched with age, sex, and height controls. Both qualitative and quantitative barium esophagram measurements for the upper, mid-, and lower vertebral bodies of C5 through T1 were analyzed in lateral, oblique, and anterior-posterior views. RESULTS: Stenotic patients versus nonstenotic controls showed no significant differences in age, sex, height, body mass index, or ethnicity. Stenosis was most commonly at the sixth cervical vertebra (C 6) lower border and C7 upper border. The mean intraesophageal minimum/maximum ratios of controls and stenotic groups in the lateral view were 0.63 ± 0.08 and 0.36 ± 0.12, respectively (P < 0.0001). Receiver operating characteristic analysis of the minimum/maximum ratios, with a <0.50 ratio delineating stenosis, demonstrated that lateral view measurements had the best diagnostic ability. The sensitivity of the radiologists' qualitative interpretation was 56%. With application of lateral intraesophageal minimum/maximum ratios, we observed improved sensitivity to 94% of the esophagram, detecting clinically significant stenosis. CONCLUSION: Applying quantitative determinants in esophagram analysis may improve the sensitivity of detecting cervical esophageal stenosis in dysphagic patients who may benefit from surgical therapy. LEVEL OF EVIDENCE: IIIb. Laryngoscope, 128:2022-2028, 2018.

Crotalus helleri venom preconditioning reduces postoperative cerebral edema and improves neurological outcomes after surgical brain injury.

INTRODUCTION: Postoperative cerebral edema is a devastating complication in neurosurgical patients. Loss of blood-brain barrier integrity has been shown to lead to the development of brain edema following neurosurgical procedures. The aim of this study was to evaluate preconditioning with Crotalus helleri venom (Cv-PC) as a potential preventive therapy for reducing postoperative brain edema in the rodent SBI model. C. helleri venom is known to contain phospholipase A2 (PLA2), an enzyme upstream to cyclooxygenase-2 (COX-2) in the inflammatory cascade, acts to increase the production of inflammatory mediators, such as prostaglandins. We hypothesize that Cv-PC will downregulate the response of the COX-2 pathway to injury, thereby reducing the inflammatory response and the development of brain edema after SBI. MATERIALS AND METHODS: 75 male Sprague Dawley rats (280-330g) were divided to the following groups-naïve+vehicle, naïve+Cv-PC, sham, vehicle, Cv-PC, Cv-PC+NS398 (COX-2 inhibitor). Vehicle preconditioned and Cv-PC animals received either three daily subcutaneous doses of saline or C. helleri venom at 72h, 48h, and 24h prior to surgery. In Cv-PC+NS398 animals, NS398 was administered intraperitoneally 1h prior to each Cv-PC injection. Sham-operated animals received craniotomy only, whereas SBI animals received a partial right frontal lobectomy. Neurological testing and brain water content were assessed at 24h and 72h after SBI; COX-2 and PGE2 expression was assessed at 24h postoperatively by Western blot and immunohistochemistry, respectively. RESULTS: At 24h after SBI, the vehicle-treated animals were observed to have increased brain water content (83.1±0.2%) compared to that of sham animals (80.2±0.1%). The brain water content of vehicle-treated animals at 72h post-SBI was elevated at 83.3±0.2%. Cv-PC-treated animals with doses of 10% LD50 had significantly reduced brain water content of 81.92±0.7% and 81.82±0.3% at 24h and 72h, respectively, after SBI compared to that of vehicle-treated animals, while Cv-PC with 5% LD50 doses showed brain water content that trended lower but did not reach statistical significance. At 24h and 72h post-SBI, Cv-PC-treated animals had significantly higher neurological score than vehicle-treated animals. The COX-2 over-expression characterized in SBI was attenuated in Cv-PC-treated animals; NS398 reversed the protective effect of Cv-PC on COX-2 expression. Cv-PC tempered the over-expression of the inflammatory marker PGE2. CONCLUSION: Our findings indicate that Cv-PC may provide a promising therapy for reducing postoperative edema and improving neurological function after neurosurgical procedures.

Crotalus atrox venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury.

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.

A Prospective Assessment of Nasopharyngolaryngoscope Recording Adaptor Use in Residency Training.

Flexible fiberoptic nasopharyngolaryngoscope (FN) examinations are important to the practice of otolaryngology (ENT). We sought to assess whether a portable recording adaptor for the FN can enhance resident learning and improve patient management. The adaptor was used prospectively on consultations by first- and second-year ENT residents, and changes in diagnosis and management were recorded in the patient care workflow. In 43 patients, we found a 23% change in diagnosis, 44% change in management, and 19% change in surgical management after an attending reviewed recorded videos. Residents and attendings reported that discussing the video enhanced learning in 88% and 81% of cases, respectively. A portable FN recording adaptor has the potential to improve resident training and perhaps lead to more prompt health care delivery.

A Model to Estimate L-Strut Strength With an Emphasis on Thickness.

IMPORTANCE: To perform and teach septorhinoplasty, one must have a principled understanding of the mechanics of the nasal septum. The thickness of the L-strut and how it changes septal strength have not been adequately quantified, yet calculating septal strength based on changes to thickness and size is vital in maintaining lasting nasal strength and integrity. OBJECTIVE: To establish standards for the nasal septal cartilage thickness, dorsal and caudal septum length, and Young's modulus. To provide a basis for quantitative, operative decision making, a mathematical model of L-strut strength is presented based on changes in thickness and width. DESIGN, SETTING, AND PARTICIPANTS: Nasal septal cartilages from 30 fresh cadavers were used to measure thickness at clinically relevant points and length of dorsal and caudal L-strut arms. The Young modulus was directly measured using a force gauge. Statistical analyses were performed to compare thicknesses in anatomically relevant areas. Using a cantilevered beam construct, the spring constant of the L-strut dorsal and caudal arms were estimated individually with width and thickness as variables. MAIN OUTCOMES AND MEASURES: Thickness, dorsal and caudal length, and the Young modulus of nasal septal cartilage. Spring constants of dorsal and caudal L-strut arms with different combinations of thickness and width. RESULTS: The mean (SD) age at death of the 30 cadavers was 79.2 (13.6) years (range 50-97 years). Of these, 17 (57%) were male, and 13 (43%) were female. The mean (SD) nasal septal cartilage thickness in the 30 cadavers was 1.45 (0.54) mm. Mean (SD) thickness of points along the 2-mm L-strut line was 1.49 (0.56) mm and was significantly thicker than points along the 5-mm L-strut line (mean [SD] thickness, 1.29 [0.52] mm) but significantly thinner than points along the 15-mm L-strut line (mean [SD] thickness, 1.68 [0.53]). Mean (SD) thicknesses of the posterior dorsal and caudal cartilage points were 1.52 (0.45) mm and 1.71 (0.69) mm and were significantly thicker than the anterior dorsal and caudal points (mean [SD] thickness, 1.28 [0.42] mm and 1.31 [0.44] mm, respectively). Mean (SD) dorsal and caudal L-strut arm lengths were 21.9 (3.7) mm and 20.9 (3.5) mm, respectively. The mean (SD) Young modulus was 2.03 (1.3) MPa. A model was generated demonstrating the thickness required to maintain a desired strength at a given dorsal or caudal arm width. CONCLUSIONS AND RELEVANCE: Although thickness was not uniform throughout the nasal septum, there is a predictable pattern. Thickness of the L-strut contributes more to septal strength than does L-strut width. The model generated in this study can be used in planning, performing, or teaching the applied mechanics of septorhinoplasty. LEVEL OF EVIDENCE: NA.

Surgical brain injury and edema prevention.

Neurosurgical procedures, carried out routinely in health institutions, present postoperative complications that result from unavoidable brain injury inflicted by surgical maneuvers. These maneuvers, which include incisions, electrocauterization, and retraction, place brain tissue at the margins of the operative site at risk of injury. Brain edema is a major complication that develops subsequent to this surgically induced brain injury. In the present review, we will discuss type of injury as well as the animal model available to study it. In addition, we will discuss potential mediators, including vascular endothelial growth factor, metalloproteinases, and cyclooxygenases, which have been tested in in vivo experimental studies and have been shown to be potential targets for the development of clinical therapies for neuroprotection against brain edema.

PAR-1 antagonist SCH79797 ameliorates apoptosis following surgical brain injury through inhibition of ASK1-JNK in rats.

Neurosurgical procedures inevitably produce intraoperative hemorrhage. The subsequent entry of blood into the brain parenchyma results in the release of large amounts of thrombin, a known contributor to perihematomal edema formation and apoptosis after brain injury. The present study seeks to test 1) the effect of surgically induced brain injury (SBI) on thrombin activity, expression of thrombin's receptor PAR-1, and PAR-1 mediated apoptosis; 2) the effect of thrombin inhibition by argatroban and PAR-1 inhibition by SCH79797 on the development of secondary brain injury in the SBI model on rats. A total of 88 Sprague-Dawley male rats were randomly divided into sham, vehicle-, argatroban-, or SCH79797-treated groups. SBI involved partial resection of the right frontal lobe under inhalation isoflurane anesthesia. Sham-operated animals received only craniotomy. Thrombin activity, brain water content, and neurological deficits were measured at 24 h following SBI. Involvement of the Ask1/JNK pathway in PAR-1-induced post-SBI apoptosis was characterized by using Ask1 or JNK inhibitors. We observed that SBI increased thrombin activity, yet failed to demonstrate any effect on PAR-1 expression. Argatroban and SCH79797 reduced SBI-induced brain edema and neurological deficits in a dose-dependent manner. SBI-induced apoptosis seemed mediated by the PAR-1/Ask1/JNK pathways. Administration of SCH79797 ameliorated the apoptosis following SBI. Our findings indicate that PAR-1 antagonist protects against secondary brain injury after SBI by decreasing both brain edema and apoptosis by inactivating PAR-1/Ask1/JNK pathway. The anti-apoptotic effect of PAR-1 antagonists may provide a promising path for therapy following SBI.

Polymerase incorporation and miscoding properties of 5-chlorouracil.

Inflammation-mediated hypochlorous acid (HOCl) can damage DNA, DNA precursors, and other biological molecules, thereby producing an array of damage products such as 5-chlorouracil (ClU). In this study, we prepared and studied 5-chloro-2'-deoxyuridine (CldU) and ClU-containing oligonucleotide templates. We demonstrate that human K-562 cells grown in culture with 10 muM CldU incorporate substantial amounts of CldU without significant toxicity. When in the template, ClU residues pair with dATP but also with dGTP, in a pH-dependent manner with incorporation by human polymerase beta, avian myeloblastosis virus reverse transcriptase (AMV-RT), and Escherichia coli Klenow fragment (exo(-)) polymerase. The enhanced miscoding of ClU is attributed to the electron-withdrawing 5-chlorine substituent that promotes the formation of an ionized ClU-G mispair. When mispaired with G, ClU is targeted for removal by human glycosylases. The formation, incorporation, and repair of ClU could promote transition mutations and other forms of heritable DNA damage.

pH-Dependent configurations of a 5-chlorouracil-guanine base pair.

Hypochlorous acid (HOCl) from activated neutrophils at sites of inflammation can react with and damage biological molecules, including nucleic acids. The reaction of HOCl with cytosine analogues can generate multiple products, including 5-chlorouracil (ClU). In this paper, we have constructed oligonucleotides containing ClU paired opposite guanine (ClU-G). Melting studies indicate that oligonucleotide duplexes containing the ClU-G mispair are substantially less stable than those containing a ClU-A base pair. The melting temperature of the ClU-G mispair is not experimentally distinguishable from that of a T-G pair. NMR studies indicate that the ClU-G base pair adopts a wobble geometry at neutral pH, similar to a T-G mispair. The exchangeable protons of the ClU-G mispair broaden rapidly with an increase in temperature, indicating that the ClU-G mispair is less stable and opens more easily than the surrounding adjacent base pairs. Unlike the ClU-A base pair studied previously [Theruvathu, J. A., et al. (2009) Biochemistry 48, 7539-7546], the ClU-G mispair undergoes a pH-dependent structural change, assuming an ionized base pair configuration that approximates a Watson-Crick base pair at higher pH. Ionization of ClU in a DNA template could promote mispair formation and mutation, in accord with previous studies on other 5-halouracil analogues. The electron-withdrawing 5-chloro substituent facilitates ionization of the ClU N3 proton, promoting mispair formation, but it also renders the glycosidic bond susceptible to base cleavage by DNA repair glycosylases.

Base pairing configuration and stability of an oligonucleotide duplex containing a 5-chlorouracil-adenine base pair.

Inflammation-mediated reactive molecules can damage DNA by oxidation and chlorination. The biological consequences of this damage are as yet incompletely understood. In this paper, we have constructed oligonucleotides containing 5-chlorouracil (ClU), one of the known inflammation damage products. The thermodynamic stability, base pairing configuration, and duplex conformation of oligonucleotides containing ClU paired opposite adenine have been examined. NMR spectra reveal that the ClU-A base pair adopts a geometry similar to that of the T-A base pair, and the ClU-A base pair-containing duplex adopts a normal B-form conformation. The line width of the imino proton of the ClU residue is substantially greater than that of the corresponding T imino proton; however, this difference is not attributed to a reduced thermal or thermodynamic stability or to an increased level of proton exchange with solvent. While the NMR studies reveal an increased level of chemical exchange for the ClU imino proton of the ClU-A base pair, the ClU residue is not a target for removal by the Escherichia coli mispaired uracil glycosylase, which senses damage-related helix instability. The results of this study are consistent with previous reports indicating that the DNA of replicating cells can tolerate substantial substitution with ClU. The fraudulent, pseudo-Watson-Crick ClU-A base pair is sufficiently stable to avoid glycosylase removal and, therefore, might constitute a persistent form of cellular DNA damage.

Incorporation of 5-chlorocytosine into mammalian DNA results in heritable gene silencing and altered cytosine methylation patterns.

Cytosine methylation patterns are essential for the proper control of gene expression in higher vertebrates. Although alterations in methylation patterns are frequently observed in human tumors, neither the mechanisms for establishing methylation patterns during normal development nor the mechanisms leading to pathological alterations of methylation patterns are currently known. While epidemiological studies have implicated inflammation in cancer etiology, a mechanistic link has yet to be established. Investigations of inflammation-mediated DNA damage may have provided important new insights. Our in vitro studies revealed that the inflammation-mediated DNA damage product, 5-chlorocytosine, could direct fraudulent methylation of previously unmethylated CpG sites. The purpose of this study was to recapitulate our in vitro findings by introducing 5-chlorocytosine residues into the DNA of replicating mammalian cells and to examine its impact on gene expression and cytosine methylation patterns. CHO-K1 cells hemizygous for the hprt gene were electroporated with the triphosphates of cytosine [2'-deoxycytidine-5'-triphosphate (dCTP)], 5-methylcytosine [5-methyl-2'-deoxycytidine-5'-triphosphate (MedCTP)] and 5'-chloro-2'-deoxycytidine-5'-triphosphate (CldCTP), and then selected with 6-thioguanine for silencing the hprt gene. Both modified nucleotides, MedCTP and CldCTP, but not unmodified dCTP, silenced hprt gene expression. Subsequent bisulfite pyrosequencing of CpG sites within the hprt promoter region of the selected cells confirmed hypermethylation, although global methylation levels as measured by gas chromatography-mass spectrometry did not change. Modified nucleotide-induced gene silencing could be reversed with 5-aza-2'-deoxycytidine indicating an epigenetic rather than mutagenic alteration. These results provide further evidence that the inflammation damage product 5-chlorocytosine could be a link between inflammation and cancer development.