Targeting the unfolded protein response in head and neck and oral cavity cancers.

Many FDA-approved anti-cancer therapies, targeted toward a wide array of molecular targets and signaling networks, have been demonstrated to activate the unfolded protein response (UPR). Despite a critical role for UPR signaling in the apoptotic execution of cancer cells by many of these compounds, the authors are currently unaware of any instance whereby a cancer drug was developed with the UPR as the intended target. With the essential role of the UPR as a driving force in the genesis and maintenance of the malignant phenotype, a great number of pre-clinical studies have surged into the medical literature describing the ability of dozens of compounds to induce UPR signaling in a myriad of cancer models. The focus of the current work is to review the literature and explore the role of the UPR as a mediator of chemotherapy-induced cell death in squamous cell carcinomas of the head and neck (HNSCC) and oral cavity (OCSCC), with an emphasis on preclinical studies.

Rhinogenic Headache in Children and Adolescents.

PURPOSE OF REVIEW: The purpose of this review is to evaluate and explain our current understanding of rhinogenic headache in the pediatric population. RECENT FINDINGS: One study showed that 40 % of pediatric patients with migraine had previously received an incorrect diagnosis of sinus headache. Two studies found that over 50% of pediatric patients with migraines have associated cranial autonomic symptoms, possibly elucidating the reasons for misdiagnosis. Some case reports demonstrate successful treatment of rhinogenic contact point headache with the surgical resection of mucosal contact points, although this diagnosis continues to be debated. Many pediatric patients diagnosed with a sinus-related headache actually meet criteria for primary headache disorders. Primary headache disorders should be considered in pediatric patients with headache and associated rhinologic symptoms. Some literature suggests that mucosal contact point headaches can be surgically treated in children, but the level of evidence is inadequate, and additional robust trials are needed.

COVID-19 and rhinology: A look at the future.

The novel Coronavirus (COVID-19) has created a deadly pandemic that is now significantly impacting the United States. Otolaryngologists are considered high risk for contracting disease, as the virus resides in the nasal cavity, nasopharynx, and oropharynx. While valuable work has been publicized regarding several topics in Rhinology, we discuss other aspects of our specialty in further detail. There are several issues regarding Rhinologic practice that need to be clarified both for the current epidemic as well as for future expected "waves." In addition, as the pandemic dies down, guidelines are needed to optimize safe practices as we start seeing more patients again. These include protocols pertinent to safety, in-office Rhinologic procedures, the substitution of imaging for endoscopy, and understanding the appropriate role of telemedicine. We discuss these aspects of Rhinology as well as practical concerns relating to telemedicine and billing, as these issues take on increasing importance for Rhinologists both in the present and the future.

Embracing telemedicine into your otolaryngology practice amid the COVID-19 crisis: An invited commentary.

The COVID-19 pandemic has quickly and radically altered how Otolaryngologists provide patient care in the outpatient setting. Continuity of care with established patients as well as establishment of a professional relationship with new patients is challenging during this Public Health Emergency (PHE). Many geographic areas are under "stay at home" or "shelter in place" directives from state and local governments to avoid COVID-19 exposure risks. Medicare has recently allowed "broad flexibilities to furnish services using remote communications technology to avoid exposure risks to health care providers, patients, and the community." [1] The implementation of telemedicine, or virtual, services, will help the Otolaryngologists provide needed care to patients while mitigating the clinical and financial impact of the pandemic. The significant coding and billing issues related to implementing telemedicine services are discussed to promote acceptance of this technology by the practicing Otolaryngologist. Of particular importance, outpatient visit Current Procedural Terminology® codes (99201-99215) may be used for telehealth visits performed in real-time audio and video.

Incorporation of telemedicine by rhinologists: The COVID-19 pandemic and beyond.

OBJECTIVES: The current analysis queries rhinologists' attitudes about the use of telemedicine, including the degree to which it has impacted practice patterns during the COVID-19 pandemic. Our objective was to survey rhinologists and understand the extent to which telemedicine serves as a rejoinder to in-person consultation: appreciation of relevant factors may be important in planning for present and future considerations. METHODS: A 14-question anonymous survey sent out to the American Rhinologic Society (ARS) membership in April 2020. It included demographic factors and detailed questions examining the extent of telemedicine use. Numerous topics including the degree of use, satisfaction with services, and utility of services were evaluated. RESULTS: There were 134 respondents. Most reported seeing ≤30% of typical in-person volume, with 14.8% not seeing any patients at all. 88.1% used telemedicine; 82.0% reported some level of satisfaction with telemedicine. The vast majority utilized platforms employing audio and video (83.3%), and a plurality reported spending 5-15 min on calls. Numerous reasons were cited for the use of telemedicine, including significant public health benefits amid the crisis (89.7%). Only 12.0% of respondents reported using telemedicine for hospital consultation. CONCLUSION: Rhinologists have embraced telemedicine during the COVID-19 pandemic in an attempt to improve accessibility, patient satisfaction, and revenue stream. When utilized appropriately, this technology obviates the need for seeing at-risk patients and performing procedures such as nasal endoscopy. Only a minority of rhinologists was dissatisfied, viewing this as a temporary fix during the pandemic.

The novel corona virus and rhinology: Impact on practice patterns and future directions.

OBJECTIVES: To evaluate the impact of the novel coronavirus pandemic on practice patterns, clinical behavior, personal health, and emotional/psychological concerns of rhinologists. METHODS: A 15-question survey was sent out to the American Rhinologic Society's (ARS) membership to determine the impact of COVID-19 during the crisis. Demographic factors and practice patterns were collected and evaluated. RESULTS: There were 224 total respondents out of 835 ARS members queried (26.8% response rate). Study queries were sent in April 2020. Notably, 17.8% reported illness in themselves or their staff and 74.4% noted a psychological/emotional impact. A plurality of rhinologists noted their practice volume and in-office procedure volume has become 20.0% and 0.0% of their prior volumes, respectively. In addition, 96.2% were noted to be using telemedicine in our subspecialty. CONCLUSION: In addition to severely impacting volume and the perception of future decreases in patients and revenue, the COVID-19 pandemic has had a physical and emotional impact on rhinologists in ways that need to be further studied. These data include significantly novel and objective information. The COVID-19 crisis also reveals the important role of telemedicine in rhinology. Guidelines regarding personal protective equipment for in-office visits, nasal endoscopy, and other in-office and operating room procedures would be particularly helpful as future waves are expected.

Rattled: Analysis of Facial Trauma Among Toddlers.

OBJECTIVE: The aim of this study was to determine the national incidence of facial trauma among toddlers and delineate patterns of injury and their causes. METHODS: A retrospective review was designed to explore patterns of maxillofacial trauma within toddler-aged children using the National Electronic Injury Surveillance System from the Consumer Product Safety Commission. The database was searched for emergency department visits involving facial trauma sustained by children 12 months through 3 years of age from 2010 through 2014 and analyzed for patient demographics, primary diagnosis, and associated products/activities. Subset analyses were performed between age groups to determine the relationship between causes of injury and age using extrapolated national incidences. RESULTS: A sample of 45,249 patients extrapolated to an estimated 1.3 million emergency department visits for facial trauma in toddlers from 2010 to 2014, averaging 260,000 annually. Injuries involving foreign bodies and fractures had a higher incidence in toddlers 2 years or older, and fractures comprised fewer than 1% of facial injuries in any age group. Furniture was the most common source of trauma overall, with a higher frequency among toddlers aged 12 to 17 months. Trauma in the setting of sports was more common in toddlers aged 3 years. CONCLUSIONS: The low incidence of facial fractures further supports recommendations against routine imaging in toddler facial trauma and suggests that more focus should be placed on investigating for concurrent traumas and soft tissue injuries where fractures are involved. Our findings highlight prevention opportunities, particularly in furniture-related injuries for toddlers aged 12 to 17 months and sports-related traumas in toddlers aged 3 years. Our study also suggests restricting certain toys from 3-year-old toddlers to decrease the risk of aspiration.

Economic Analysis of Using Free Fat Graft or Acellular Dermis to Prevent Post-parotidectomy Frey Syndrome.

A decision tree was constructed to determine the incremental cost-effectiveness ratio (ICER) of grafting techniques used to prevent Frey Syndrome. The authors performed a sensitivity analysis to calculate what the probability of preventing Frey Syndrome would have to be and maximum costs associated with using grafting techniques to warrant their use as more "cost-effective" choice than using neither. Decision pathways utilized were uses of (1) free fat graft (FFG), (2) acellular dermis, and (3) no grafting. The probability of developing Frey syndrome and costs were extracted from previous studies to construct the decision tree. The primary effectiveness was the ICER of FFG or acellular dermis to prevent Frey syndrome. The initial outcomes included preventing Frey syndrome (effectiveness = 1) or developing Frey syndrome (effectiveness = 0). Compared with not using a graft, the ICER of using FFG and acellular dermis were $10,628 and $50,813, respectively. Frey syndrome was found in 2.6% of patients postoperatively in FFG group, 9.8% of patients in acellular dermis group, and 30.7% of patients who did not have a graft. The ICER shows absolute dominance of FFG with lower cost and high effectiveness over acellular dermis. This economic evaluation strongly supports the use of FFG over acellular dermis as cost-effective approach for prevention of postparotidectomy Frey syndrome.

Inpatient Complications After Transsphenoidal Surgery in Cushing's Versus Non-Cushing's Disease Patients.

OBJECTIVE: Transsphenoidal surgery (TSS) harbors a potential for hypopituitarism, cerebrospinal fluid (CSF) leaks, and other complications. We utilized the Nationwide Inpatient Sample Database (NIS) to compare inpatient complication rates between Cushing's disease (CD) and non-Cushing's disease (NCD) patients undergoing TSS. METHODS: Inpatient hospitalization data for 960 CD and 12 110 NCD patients who underwent TSS between 2002 and 2010 were accessed. Demographic information, outcomes, and complication rates were evaluated. RESULTS: Patients with CD had a female predilection (81.7%) and were younger (40.5 ± 14.4 years) than NCD patients (47.8% female; 52.1 ± 16.3 years) (P < .001). Length of stay and total charges did not differ between groups. Patients with CD had significantly greater postoperative diabetes insipidus rates (14.0% vs 9.6%, P < .001) and urinary/renal complications (1.7% vs 0.9%, P = .027). After adjusting for possible confounders, the relationship between urinary/renal complications and CD status strengthened. There was no difference in rates of CSF leak and iatrogenic pituitary disorders overall. CONCLUSION: No differences were noted in the rate of early CSF leaks between postoperative TSS CD and NCD patients. Postoperative diabetes insipidus did not significantly differ between groups after adjusting for confounders. Only odds of urinary/renal complications in CD patients was significant after adjustment.

A comparison of plaintiff and defense expert witness qualifications in malpractice litigation in anesthesiology.

BACKGROUND: Expert witnesses serve a crucial role in the medicolegal system, interpreting evidence so that it can be understood by jurors. Guidelines have been established by both the legal community and professional medical societies detailing the expectations of expert witnesses. The primary objective of this analysis was to evaluate the expertise of anesthesiologists testifying as expert witnesses in malpractice litigation. METHODS: The WestlawNext legal database was searched for cases over the last 5 years in which anesthesiologists served as expert witnesses. Internet searches were used to identify how long each witness had been in practice. Departmental websites, the Scopus database, and state medical licensing boards were used to measure scholarly impact (via the h-index) and determine whether the witness was a full-time faculty member in academia. RESULTS: Anesthesiologists testifying in 295 cases since 2008 averaged over 30 years of experience per person (mean ± SEM, defense, 33.4 ± 0.7, plaintiff, 33.1 ± 0.6, P = 0.76). Individual scholarly impact, as measured by h-index, was found to be lower among plaintiff experts (mean ± SEM, 4.8 ± 0.5) than their defendant counterparts (mean ± SEM, 8.1 ± 0.8; P = 0.02). A greater proportion of defense witnesses were involved in academic practice (65.7% vs 54.8%, P = 0.04). CONCLUSIONS: Anesthesiologists testifying for both sides are very experienced. Defense expert witnesses are more likely to have a higher scholarly impact and to practice in an academic setting. This indicates that defense expert witnesses may have greater expertise than plaintiff expert witnesses.

Craniofacial Surgery and Adverse Outcomes: An Inquiry Into Medical Negligence.

OBJECTIVE: This study aimed to evaluate factors contributing to medical negligence relevant to craniofacial surgery. METHODS: Retrospective analysis of verdict and settlement reports on the Westlaw legal database for outcome, awards, physician defendants, and other specific factors raised in malpractice litigation. RESULTS: Of 42 verdicts and settlement reports included, 52.4% were resolved with either an out-of-court settlement or plaintiff verdict, with aggregate payments totaling $50.1M (in 2013 dollars). Median settlements and jury-awarded damages were $988,000 and $555,000, respectively. Payments in pediatric cases ($1.2M) were significantly higher. Plastic surgeons, oral surgeons, and otolaryngologists were the most commonly named defendants. The most common alleged factors included intraoperative negligence (69.0%), permanent deficits (54.8%), requiring additional surgery (52.4%), missed/delayed diagnosis of a complication (42.9%), disfigurement/scarring (28.6%), postoperative negligence (28.6%), and inadequate informed consent (20.6% of surgical cases). Failure to diagnose a fracture (19.0%) and cleft-reparative procedures (14.3%) were the most frequently litigated entities. CONCLUSION: Medical negligence related to craniofacial surgery involves plaintiffs in a wide age range as well as physician defendants in numerous specialties, and proceedings resolved with settlement and plaintiff verdict involve substantial payments. Cases with death, allegedly permanent injuries, and pediatric plaintiffs had significantly higher payments.

Academic Benchmarks for Otolaryngology Leaders.

OBJECTIVE: This study aimed to characterize current benchmarks for academic otolaryngologists serving in positions of leadership and identify factors potentially associated with promotion to these positions. METHODS: Information regarding chairs (or division chiefs), vice chairs, and residency program directors was obtained from faculty listings and organized by degree(s) obtained, academic rank, fellowship training status, sex, and experience. Research productivity was characterized by (a) successful procurement of active grants from the National Institutes of Health and prior grants from the American Academy of Otolaryngology-Head and Neck Surgery Foundation Centralized Otolaryngology Research Efforts program and (b) scholarly impact, as measured by the h-index. RESULTS: Chairs had the greatest amount of experience (32.4 years) and were the least likely to have multiple degrees, with 75.8% having an MD degree only. Program directors were the most likely to be fellowship trained (84.8%). Women represented 16% of program directors, 3% of chairs, and no vice chairs. Chairs had the highest scholarly impact (as measured by the h-index) and the greatest external grant funding. CONCLUSION: This analysis characterizes the current picture of leadership in academic otolaryngology. Chairs, when compared to their vice chair and program director counterparts, had more experience and greater research impact. Women were poorly represented among all academic leadership positions.

Voicing an impact: who does the National Institutes of Health support for voice disorder research?

PURPOSE: Interest in a variety of neoplastic, functional, neurological, and age-related laryngeal disorders has contributed to the development of laryngology as an established subspecialty. Funding support plays a critical role in facilitating scholarship within the field. Our objectives were to evaluate who is receiving funding from the NIH for topics relevant to voice disorders, and further describe temporal trends in grants awarded. METHODS: The NIH RePORTER database was searched for grants relevant to voice disorders. Data were further organized by PI specialty, academic department, and funding totals. Furthermore, PI scholarly impact, as measured by the h-index, was calculated. RESULTS: A total of 830 funded fiscal years (for 232 unique projects) totaling $203 million have supported projects examining voice disorders. A plurality of projects (32.8%) was awarded to PIs in otolaryngology departments, followed by 17.2% to speech pathology/communication sciences departments. Although year-to-year variation was noted, otolaryngology departments received approximately 15% of funding annually. Funded otolaryngologists had similar scholarly impact values to individuals in other specialties. CONCLUSIONS: The study of voice disorders involves an interdisciplinary approach, as PIs in numerous specialties receive NIH funding support. As they receive a considerable proportion of this funding and had similar h-indices compared to other specialties involved, otolaryngologists have just as much scholarly impact despite being a smaller specialty. As speech and language pathologists also comprised a significant proportion of individuals in this analysis, enhanced cooperation and encouragement of interdisciplinary scholarly initiatives may be beneficial.

Cleft palate: a clinical review.

Orofacial clefts, including cleft palates (CP), are one of the most common birth defects. CP have a multiplicity of effects on the individual and society in terms of economic costs, loss of productivity, psychosocial effects, and increased morbidity and mortality at all stages of life. Embryological development of the palate is well delineated, with developments in the last decade regarding the biomolecular processes involved. Etiology is complex, involving a number of genetic and environmental factors. Various techniques can be employed for the repair of CP, depending on whether the cleft is of the primary or secondary palate, the width of the cleft, whether lengthening of the palate is necessary, and with regard to concerns of disruption of midfacial growth. All surgical techniques have the goals of restoring functional speech, swallowing, and aesthetics. A multidisciplinary team is necessary for the long-term pre- and postoperative care of CP patients to handle complications, associated anomalies, and to optimize function and quality of life.

The association between scholarly impact and National Institutes of Health funding in ophthalmology.

OBJECTIVE: To examine whether there is an association between scholarly impact, as measured by the h-index, academic rank, and National Institutes of Health (NIH) awards in academic ophthalmology. DESIGN: Retrospective analysis of NIH RePORTER and Scopus databases. PARTICIPANTS: Not applicable. METHODS: Five hundred seventy-three NIH awards to 391 primary investigators (PIs) in ophthalmology departments were examined. Grant recipients were organized by academic rank, obtained from online listings, and h-index, calculated using the Scopus database. Non-NIH-funded faculty from 20 randomly chosen academic ophthalmology departments also were organized by rank and h-index for comparison with their NIH-funded colleagues. MAIN OUTCOME MEASURES: Scholarly impact, as measured by the h-index, and NIH funding. RESULTS: The h-index increased with successive academic rank among non-NIH-funded and NIH-funded faculty, as did NIH funding among the latter group. The NIH-funded faculty had higher scholarly impact, as measured by the h-index, than their non-NIH-funded PIs (h = 18.3 vs. 7.8; P <0.0001), even when considering publications only in the prior 5 years; h-index increased with increasing NIH funding ranges. The h-indices of those holding an MD degree (21.4±1.6 standard error of mean) were not statistically higher than those of PhD holders (17.9±0.6) and those with both an MD and PhD degree (18.1±1.7; P = 0.14). CONCLUSIONS: The h-index increases with increasing academic rank among NIH-funded and non-NIH-funded faculty in ophthalmology departments. This bibliometric is associated strongly with NIH funding because NIH-funded PIs had higher scholarly impact than their non-NIH-funded colleagues, and increasing impact was noted with higher funding. The h-index is an objective and easily calculable measure that may be valuable as an adjunct in assessing research productivity, a significant factor for academic promotion in academic ophthalmology.

Clinical pearls in endoscopic sinus surgery: key steps in preventing and dealing with complications.

Increasing prevalence of patients undergoing endoscopic sinus surgery (ESS) makes understanding methods to preventing complications important to otolaryngologists. This commentary details clinical pearls and perioperative strategies that may minimize complications and increase preparedness for appropriate decision making in the event of a complication. Preoperative preparation is an important factor in preventing adverse events in ESS. This includes ensuring the presence of objective radiographic findings before pursuing operative management, both for patients' safety as well as medicolegal reasons, and providing adequate preoperative patient education. Appreciating variants in skull base and orbital wall anatomy through preoperative imaging is crucial for avoidance of intracranial and orbital complications. The importance of optimal visualization intraoperatively and the appropriate role of CT-guided imaging are also discussed. Finally, strategies for dealing with postoperative sequelae of more common complications are noted. This article represents a brief review for introductory sinus surgeons and is not meant as an all encompassing review.

Management of sinonasal teratocarcinosarcoma: a systematic review.

PURPOSE: Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly malignant neoplasm that often involves the anterior skull base. This study reviews the published literature related to SNTCS. Clinical presentation, demographics, radiographic diagnosis, pathology, treatment, and management outcomes of this uncommon disease are reported. METHODS: A systematic review in the published English literature was conducted. A MEDLINE/PubMed search and bibliographic examination of articles pertaining to SNTCS were performed. Each case was analyzed for patient demographics, clinical presentation, tumor location, diagnosis, treatment, and survival outcome. RESULTS: A total of 49 journal articles were included. Individual patient data were reported in 86 cases. The average age of the patients was 54.5 years (range, 0.1 to 85 years), with a strong male predilection (7:1). Average follow-up was found to be 38.9 months (range, 2 to 372 months). The most common treatment method was surgery with radiation therapy, utilized in 59.3% of patients. Out of 71 cases with reported outcome and follow-up, there were 21 cases of recurrence, 8 cases with metastasis, and 6 cases reporting both recurrence and metastasis. Forty-two out of 71 (59.2%) patients survived at the time of follow-up. CONCLUSIONS: This study describes the largest pool of SNTCS patients to date. SNTCS is a rare and aggressive malignant skull base tumor with a poor prognosis with frequent recurrence and metastasis. Although a variety of treatment paradigms have been reported in the literature, radical surgical resection followed by radiation therapy appears to be the most commonly used treatment option.

Meningitis and legal liability: an otolaryngology perspective.

PURPOSE: Meningitis is a potential complication in otolaryngologic procedures and conditions. Severe sequelae make understanding factors involved in relevant malpractice litigation critical. We analyze pertinent litigation for awards, outcomes, patient demographic factors, and other alleged causes of malpractice. METHODS: Pertinent jury verdict and settlement reports were examined using the Westlaw legal database (Thomson Reuters, New York, NY). RESULTS: Twenty-three cases (60.5%) involved non-iatrogenic injuries, including inadequate treatment or failure to diagnose sinusitis or otitis media, while 15 (39.5%) involved iatrogenic cases, mostly rhinologic procedures. 36.8% of cases were resolved for the defendant, 28.9% with juries awarding damages, and 34.2% with settlements. Although not statistically significant, mean damages awarded were higher than settlements ($2.1 vs. 1.5M, p=0.056), and cases involving pediatric patients were more likely to be resolved with payment than those with adult litigants (80.0% vs. 52.2%, p=0.08 respectively). Other frequent alleged factors included permanent deficits (63.2%), requiring additional surgery (41.1%), death (34.2%), cognitive deficits (21.2%), deafness (15.8%), and inadequate informed consent (33.0% of iatrogenic cases). CONCLUSIONS: Practitioners facing litigation related to meningitis may wish to consider these findings, notably for cases involving death or permanent functional deficits, as cases with out of court settlements tended to be resolved with lower payments. Cases involving misdiagnosis may be more likely to be resolved with payment compared with iatrogenic cases. By understanding the issues detailed in this analysis and including them in the informed consent process for patients undergoing rhinologic and otologic procedures, otolaryngologists may potentially improve patient safety and decrease liability.

In the eyes of the law: malpractice litigation in oculoplastic surgery.

PURPOSE: To assess characteristics associated with various outcomes of malpractice litigation, resulting from injuries sustained during oculoplastic procedures. METHODS: The Westlaw legal database (Thomson Reuters, New York, NY, U.S.A.) was used to obtain jury verdicts and settlements. Pertinent data were extracted from 69 malpractice cases litigated from 1988 to 2012 involving oculoplastic procedures, including alleged cause of malpractice, outcome, and defendant specialty. RESULTS: The most commonly litigated surgical procedures were blepharoplasty (63.8% of total) and brow lift surgery (11.6%). The most commonly alleged complications included excessive scarring (24.6%), lagophthalmos (24.6%), visual defects (23.2%), and exposure keratitis (21.7%). Plastic surgeons were the most commonly named defendants (46.4%), followed by both comprehensive ophthalmologists and fellowship-trained ophthalmic plastic surgeons (17.3% each). A defense verdict was held in 60.9% of cases, a plaintiff verdict in 31.9% of cases, and a settlement was reached in 7.2% of cases. Blindness, cranial nerve injury, and the allegation of a permanent deficit increased the likelihood of a case being resolved with payment to the plaintiff (Fisher exact tests, p < 0.05). CONCLUSIONS: Most litigated oculoplastic malpractice cases were resolved in favor of the defendant, while settlements and plaintiff decisions averaged $455,703. Blepharoplasty constituted two-thirds of cases, with the most frequently cited associated complications being unsightly scarring, lagophthalmos, and visual deficits. An alleged lack of informed consent (30.4%) or the need for additional surgery (39.1%) was present in a considerable proportion of cases, emphasizing the importance of a detailed informed consent and clear communication preoperatively regarding patient expectations.