Chemosensory function recovery in COVID-19 patients: A cross-sectional study.

OBJECTIVE: To determine whether subjects who have recovered from COVID-19 smell and taste disturbance perform similarly to their COVID-naïve baseline, on gold-standard smell and taste tests. STUDY DESIGN: Prospective cross-sectional study. SETTING: University of Miami Department of Otolaryngology in Miami, FL between September 2021, and August 2022. METHODS: Those previously COVID-19 positive composed the experimental group, those who reported being COVID-naïve composed the control group. Mean total score for the UPSIT Smell Test, and the Burghart Taste Strip test were the primary outcome measures. RESULTS: 70 adult subjects (35 former COVID-positive, 35 COVID-naïve) were enrolled, with 21 females and 14 males in each group. 87 % of all subjects were white and were almost distributed evenly between Hispanic and non-Hispanic. Mean UPSIT total score for the experimental group was 30.6 (95 % CI 28.9-32.3), mean UPSIT total score for the control group was 31.2 (95 % CI 29.7-32.8). Mean Burghart total score for the experimental group was 11.3 (95 % CI 10.6-12.0), mean Burghart total score for the control group was 10.7 (95 % CI 9.7-11.8). These showed a significant overlap of the 95 % CI of the mean total score between the control group and the experimental group, suggesting no significant difference between the two groups. CONCLUSION: These results suggest that COVID-19 patients who experience smell and taste disturbance and recover, regain sensory ability similar to their pre-COVID ability. Further study is needed to validate these findings, but the results are promising in the long-term recovery of COVID-19.

Opiate vs non-opiate prescription medication for pain control after endoscopic sinus surgery for chronic rhinosinusitis.

PURPOSE: Research indicates that most providers give opiates after endoscopic sinonasal surgery. The effectiveness of non-opiate medications after sinonasal surgery is poorly understood and most studies do not assess medication failure. This study compares oral opiate, oral opiate and topical steroid, and oral non-opiate pain control. Patient call-backs are used as a proxy for pain medication failure. MATERIALS AND METHODS: This study compares three medication regiments after sinonasal surgery for 180 adults with chronic rhinosinusitis. Patients were instructed to take acetaminophen for mild pain. For moderate/severe pain, patients used: 1) oxycodone-acetaminophen, 2) oxycodone-acetaminophen + budesonide nasal rinses, or 3) meloxicam + acetaminophen. Patients were instructed to call clinic if pain was not controlled. Descriptive statistics compared cohorts. Chi-square tests compared call-backs between cohorts. Logistic regression adjusted for baseline differences in covariates, comorbidities, and operative sites. RESULTS: Cohorts had similar age, sex distribution, disease features, and extent of surgery. The meloxicam cohort had less subjects with pain disorders. The oxycodone cohort had less subjects with diabetes, septoplasty, and turbinate reduction. After adjusting for baseline differences and using oxycodone as the reference group (n = 50), the odds of calling clinic for poorly controlled pain was 0.18 (95% Confidence Interval (CI): 0.05-0.6) in the meloxicam cohort (n = 45) and 0.19 (95% CI:0.07-0.5) in the oxycodone + budesonide rinses cohort (n = 85). CONCLUSION: In this study, both meloxicam and oxycodone + budesonide rinses were more effective at controlling pain after sinonasal surgery than oxycodone alone.

Reporting of Participants' Sex, Race, Ethnicity, and Socioeconomic Status in Pituitary Surgery Literature.

Introduction Social determinants of health (SDOH) are associated with differential outcomes after pituitary tumor treatment. However, the specific impact of SDOH is not well characterized. One reason may be the lack of collection and reporting of sociodemographic variables in the literature. This study aims to evaluate the frequency of reporting and distribution of participants' sex, race, ethnicity, income, and education level within pituitary surgery literature. We will compare the reported clinical research population demographics to the 2020 U.S. census. Methods A systematic review was performed by searching PubMed, Cochrane, and Embase databases for pituitary surgery clinical research published between July 1, 2021 to June 30, 2022. We excluded studies that lacked a comparison group, were not original research (i.e., systematic reviews, meta-analysis), or included national databases and registry data. Results The final analysis included 92 studies. A total of 99% of studies collected data on subject sex. On average 49% (range: 14-100%) of study populations were male. Only 4% ( n = 4) studies included racial demographic data. Two studies included information on participants' ethnicity and two included education background. No studies included income or insurance data. Four U.S. studies included demographic distribution, and the reported race and ethnicity percentages are similar to the U.S. 2020 census distribution. Conclusion Most clinical pituitary research collects and reports data on participant sex. However, very few studies collect and report data on other sociodemographic variables that can play a role in outcomes. The lack of sociodemographic information in clinical research literature makes it difficult to determine the role of SDOH on pituitary surgery outcomes.

Treatment of unilateral olfactory neuroblastoma: Appropriate extent of surgical resection and potential for olfactory preservation.

Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patient's quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low-grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease-free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes.

American Rhinologic Society expert practice statement part 2: Postoperative precautions and management principles following endoscopic skull base surgery.

The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence regarding postoperative precautions for patients following endoscopic skull base surgery for intradural pathology. These topics include the administration of postoperative nasal hygiene; patient mobilization and activity level; the resumption of continuous positive airway pressure in patients with obstructive sleep apnea; and the timing and capacity with which a patient may be subjected to barotrauma, such as air travel postoperatively. This EPS was developed following the recommended methodology and approval process as previously outlined. Given the diverse practices and limited agreement on the accepted principles regarding postoperative precautions for patients following skull base surgery, this EPS seeks to summarize the existing literature and provide clinically relevant guidance to bring clarity to these differing practice patterns. Following a modified Delphi approach, four statements were developed, all of which reached consensus. Because of the paucity of literature on these topics, these statements represent a summation of the limited literature and the experts' opinions. These statements and the accompanying evidence are summarized below, along with an assessment of future needs.

American Rhinologic Society expert practice statement part 1: Skull base reconstruction following endoscopic skull base surgery.

The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence for technical factors that optimize outcomes in skull base reconstruction following endoscopic skull base surgery for intradural pathologies. These topics include the use of free mucosal grafts versus vascularized pedicled nasoseptal flaps; the use of autologous versus synthetic grafts; and the roles of lumbar drains, dural sealants, and nasal packing. This EPS was developed following the recommended methodology and approval process as previously outlined. As there are a myriad of techniques and limited agreement on the accepted principles of skull base reconstruction, this EPS aims to summarize the existing evidence and provide clinically meaningful guidance on these divergent practices. Following a modified Delphi approach, five statements were developed, four of which reached consensus and one of which reached near consensus. These statements and the accompanying evidence are summarized along with an assessment of future needs.

Frontal lobe position after single-layer cadaveric dermal matrix repair of large anterior skull base defects.

Objective: Endoscopic repair of large anterior skull base (ASB) defects has excellent results when using multilayered repairs with a nasoseptal flap. However, in extensive intranasal tumors, a nasoseptal flap may not always be available. One alternative option is a flexible single-layer ASB repair. Initial studies indicate low cerebrospinal fluid leak rates with a single-layer repair. However, the level of frontal lobe support, particularly the propensity for a significant inferior displacement of the frontal lobe, is not known. The goal of this study is to determine the frontal lobe position after single-layer acellular dermal allograft repair in large ASB defects. Study Design: Retrospective cohort study. Setting: Tertiary care medical center. Subjects and Methods: This cohort study compares the frontal lobe position in adults who underwent endoscopic endonasal ASB tumor resection and single-layer cadaveric dermal matrix repair (ASB cohort) with control subjects without intracranial abnormalities (control cohort). The ASB cohort includes subjects with an ASB defect of ≥5 cm anterior/posterior and ≥1.5 cm wide and who had imaging at least 2 months after surgery. The frontal lobe position is measured on sagittal CT/MRI using a reference line from the base of the sella to the nasion. A value of zero indicates that the inferior-most aspect of the frontal lobe is at the level of the nasion-sellar line. A positive value indicates that the frontal lobe is inferior to the nasion-sellar line. The ASB cohort frontal lobe position is compared with the control cohort using the Mann-Whitney U test. A priori we set an absolute difference of 5 mm as a clinically significant difference. Results: The ASB cohort includes 47 subjects who are 57% male with an average age of 60 years (range: 31-89 years). The most common ASB pathology is esthesioneuroblastoma (n = 21) and 81% of the ASB cohort had postoperative radiation. The control cohort includes 20 subjects who are 60% male, with a mean age of 45 years (range: 19-74 years). The majority of controls underwent imaging for head trauma (n = 13). The ASB mean frontal lobe position is -0.2 mm superior to the nasion-sellar line (range: -9.2 to 10.4 mm), while the control's mean frontal lobe position is 1.1 mm inferior to the nasion-sellar line. This difference is not statistically significant (P = 0.13) and does not reach our a priori definition of clinical significance. The frontal lobe position of ASB subjects who had radiation is closer to the nasion-sellar line as compared with those who did not undergo radiation. Conclusions: Single-layer acellular dermal graft repair maintains frontal lobe support and position in large ASB defects.

Multidisciplinary Postoperative Care Pathway to Reduce Readmissions following Endoscopic Transsphenoidal Pituitary Surgery: Improving Quality of Patient Care.

Background Thirty-day unplanned readmission following endoscopic transsphenoidal pituitary surgery (ETPS) occurs in up to 14% of patients. Delayed hyponatremia is one of the most common causes, accounting for 30% of readmissions and often occurs within 1 week of surgery. The authors' prior retrospective review identified endocrinology follow-up as protective factor. Objectives Implementation of a multidisciplinary postoperative care (POC) pathway: (1) to reduce 30-day hospital readmissions following ETPS and (2) improve inpatient and outpatient coordination of care with endocrinologist. Methods This study is a single institution temporal cohort study of patients prior to (control cohort) and after implementation of the POC pathway (intervention cohort). The POC pathway utilized postdischarge 1 to 1.5 L/d fluid restriction, postoperative days 5 to 7 serum sodium, and endocrinology follow-up within 1 week of discharge to stratify patients into tiered hyponatremia regimens. Results A total of 542 patients were included in the study, 409 (75%) in the control cohort and 133 (25%) in the intervention cohort. All-cause readmission was significantly reduced following implementation of the POC pathway (14 vs. 6%, p = 0.015). Coordination with endocrinologist significantly increased in the inpatient (96 vs. 83%, p < 0.001) and outpatient (77 vs. 68%, p = 0.042) settings. Patients who were not in the POC pathway had the highest risk of readmission (odds ratio: 2.5; 95% confidence interval: 1.1-5.5). Conclusion A multidisciplinary POC pathway incorporating endocrinologist in conjunction with postdischarge weight-based fluid restriction and postoperative serum sodium levels can safely be used to reduce 30-day readmissions following ETPS.

Retrospective Review of Surgical Site Infections after Endoscopic Endonasal Sellar and Parasellar Surgery: Multicenter Quality Data from the North American Skull Base Society.

Introduction Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes. Methods We conducted a multicenter retrospective analysis of shared quality data points for the endoscopic endonasal approach (EEA) for pituitary adenomas, along with other sellar and parasellar region masses that were included by participating institutions. Patient and operative characteristics, perioperative and postoperative antibiotic regimens and their durations, intraoperative and postoperative cerebrospinal fluid leak, and onset of postoperative meningitis and sinusitis were compared. Results Fifteen institutions participated and provided 6 consecutive months' worth of case data. Five hundred ninety-three cases were included in the study, of which 564 were pituitary adenomectomies. The incidences of postoperative meningitis and sinusitis were low (0.67 and 2.87% for all pathologies, respectively; 0.35% meningitis for pituitary adenomas) and did not correlate with any specific antibiotic regimen. Immunocompromised status posed an increased odds of meningitis in pituitary adenomectomies (28.6, 95% confidence interval [1.72-474.4]). Conclusions The results show no clear benefit to postoperative antimicrobial use in EEA, with further larger studies needed.

Chronic Rhinosinusitis Disease Disparity in the South Florida Hispanic Population.

OBJECTIVES/HYPOTHESIS: The role of social determinants of health in chronic rhinosinusitis (CRS) is poorly characterized. Limited research examining CRS health disparities indicates that minority status is associated with worse CRS. However, many of these studies are retrospective or performed in populations without substantial ethnic minorities. Rhinologists need to characterize existing CRS disease disparities to develop targeted strategies for improving care in these populations. This prospective study assesses preoperative CRS disease burden in South Florida (SFL) Hispanic and non-Hispanic patients and examines potential factors contributing CRS disease disparities. STUDY DESIGN: Prospective cohort study. METHODS: The prospective cohort study included consecutive patients having primary endoscopic sinus surgery (ESS) for CRS between September 2019 and February 2020 with complete preoperative data. Data were collected in clinic and surgery. Descriptive statistics compare Hispanic and non-Hispanic cohorts. Linear regression adjusts for confounders. Relative risk (RR) compared CRS severity markers. RESULTS: Thirty-eight Hispanic and 56 non-Hispanic patients met inclusion criteria. Age, sex, CT scores, insurance payer, and comorbidities were similar between cohorts. Hispanics presented with worse 22-item Sinonasal Outcome Test (SNOT-22) (55; SD = 18) compared to non-Hispanics (37; SD = 22) (P < .001). Hispanics tended to have a higher risk of severe CRS markers, including nasal polyps RR = 2.5 (95% CI: 1.0-5.9), neo-osteogenesis RR = 1.6 (95% CI: 0.5-4.7), extended procedures (i.e., draft III) RR = 2.97 (95% CI: 1.0-9.1), and tissue eosinophilia RR = 1.46 (95% CI: 0.6-3.5). Hispanics reported longer sinonasal symptom duration. CONCLUSIONS: SFL hispanic patients presenting for primary ESS have worse sinonasal disease burden. SFL Hispanics have markers of greater CRS severity and report longer delays before receiving CRS care. These factors may contribute to increased sinonasal disease burden in Hispanic patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2659-2665, 2021.

American Rhinologic Society expert practice statement: Postoperative pain management and opioid use after sinonasal surgery.

The goal of this American Rhinologic Society expert practice statement (EPS) is to provide clinically applicable, evidence-based recommendations regarding pain management in sinonasal surgery. This EPS was developed following the recommended methodology and approval process as previously outlined. The topics of interest included preoperative counseling, local anesthesia, use of opioids for postoperative pain, use of nonopioid medication for postoperative pain, nonsteroidal anti-inflammatory drugs and bleeding, and use of gabapentin for pain control. Following a modified Delphi approach, 6 statements were developed, 5 of which reached consensus and 1 that did not. These statements and accompanying evidence are summarized along with an assessment of future needs.

Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the referral of adults with obstructive sleep apnea (OSA) for surgical consultation. METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of upper airway sleep apnea surgery or bariatric surgery to no treatment as well as studies that reported on patient-important and physiologic outcomes pre- and postoperatively. Statistical analyses were performed to determine the clinical significance of using surgery to treat obstructive sleep apnea in adults. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for making recommendations. RESULTS: The literature search resulted in 274 studies that provided data suitable for statistical analyses. The analyses demonstrated that surgery as a rescue therapy results in a clinically significant reduction in excessive sleepiness, snoring, blood pressure (BP), apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index (ODI); an increase in lowest oxygen saturation (LSAT) and sleep quality; and an improvement in quality of life in adults with OSA who are intolerant or unaccepting of positive airway pressure (PAP) therapy. The analyses demonstrated that surgery as an adjunctive therapy results in a clinically significant reduction in optimal PAP pressure and improvement in PAP adherence in adults with OSA who are intolerant or unaccepting of PAP due to side effects associated with high pressure requirements. The analyses also demonstrated that surgery as an initial treatment results in a clinically significant reduction in AHI/RDI, sleepiness, snoring, BP, and ODI and an increase in LSAT in adults with OSA and major anatomical obstruction. Analysis of bariatric surgery data showed a clinically significant reduction in BP, AHI/RDI, sleepiness, snoring, optimal PAP level, BMI, and ODI and an increase in LSAT in adults with OSA and obesity. Analyses of very limited evidence suggested that upper airway surgery does not result in a clinically significant increase in risk of serious persistent adverse events and suggested that bariatric surgery may result in a clinically significant risk of iron malabsorption that may be managed with iron supplements. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12):2507-2531.

Imaging Characteristics of a Hypervascular Pituitary Spindle Cell Oncocytoma on Magnetic Resonance Imaging and Digital Subtraction Angiography.

BACKGROUND: Spindle cell oncocytomas (SCOs) are rare neuroendocrine tumors of the posterior pituitary that are often misdiagnosed as nonfunctional pituitary tumors. Fewer than 50 cases of SCOs have been described in the literature, and many of these reports have documented the tumors to be hypervascular on imaging or histology. CASE DESCRIPTION: We present the first cerebral angiography imaging findings of an SCO before primary resection. The discovery of a prominent tumor blush, enlarged meningohypophyseal feeders bilaterally, and prominent tumor draining veins aided in preoperative planning and subsequent successful endoscopic transsphenoidal surgical resection. CONCLUSIONS: Despite being a rare entity, SCOs should be included in the differential diagnosis when working up a hypervascular sellar tumor. Flow voids may be present on initial magnetic resonance imaging evaluation. Subsequent digital subtraction angiography can be used to further investigate abnormal vasculature and aid in surgical planning.

Olfactory and Gustatory Dysfunction as An Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

OBJECTIVE: Evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in COVID-19 patients Study Design: Multicenter Case Series Setting: 5 tertiary care hospitals (3 in China, 1 in France, 1 in Germany) Subjects and Methods: 394 PCR confirmed COVID-19 positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and Visual Analogue Scale (VAS) were used to quantify olfactory and gustatory dysfunction respectively. All subjects at one hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n=239), German (n=39) and French (n=116) cohorts were 32%, 69%, and 49% 138 respectively. The median age of included subjects was 39 years old, 92/161 (57%) were male, and 10/161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10/90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. 43% (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of SARS-CoV-2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study.

OBJECTIVE: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN: Multicenter case series. SETTING: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). SUBJECTS AND METHODS: In total, 394 polymerase chain reaction (PCR)-confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Long-term complications of septal dermoplasty in patients with hereditary hemorrhagic telangiectasia.

OBJECTIVE: Septal dermoplasty has been recommended as the treatment of choice for life-threatening epistaxis in patients with hereditary hemorrhagic telangiectasia. This study evaluates the complications of septal dermoplasty in the management of transfusion-dependent epistaxis. STUDY DESIGN: Consecutive retrospective study. SUBJECTS AND METHODS: Between 1994 and 2006, septal dermoplasty was performed on 106 consecutive patients with transfusion dependent epistaxis. Of 103 potential patients, 37 either died or were lost to follow-up, which left 66 patients for study. Data on complications and quality of life were collected on 50 (76%) of 66 patients (mean follow-up, 3.75 years) via phone interview. RESULTS: Seventy-eight percent experienced nasal odor; 72% had nasal crusting; 58% had decreased sense of smell; 30% noted worsened sinus infection; 88% could breathe through their nose; 86% stated improved quality of life. CONCLUSION: Septal dermoplasty remains an effective way of treating transfusion dependent epistaxis in patients with hereditary hemorrhagic telangiectasia and subjectively improves their quality of life.

The efficiency of protein compartmentalization into the secretory pathway.

Numerous proteins targeted for the secretory pathway are increasingly implicated in functional or pathological roles at alternative cellular destinations. The parameters that allow secretory or membrane proteins to reside in intracellular locales outside the secretory pathway remain largely unexplored. In this study, we have used an extremely sensitive and quantitative assay to measure the in vivo efficiency of signal sequence-mediated protein segregation into the secretory pathway. Our findings reveal that segregation efficiency varies tremendously among signals, ranging from >95 to <60%. The nonsegregated fraction is generated by a combination of mechanisms that includes inefficient signal-mediated translocation into the endoplasmic reticulum and leaky ribosomal scanning. The segregation efficiency of some, but not other signal sequences, could be influenced in cis by residues in the mature domain or in trans by yet unidentified cellular factors. These findings imply that protein compartmentalization can be modulated in a substrate-specific manner to generate biologically significant quantities of cytosolically available secretory and membrane proteins.

Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb+/- mice.

Mice with a single copy of the retinoblastoma gene (Rb(+/-)) develop a syndrome of multiple neuroendocrine neoplasia. They usually succumb to fast-growing, Rb-deficient melanotroph tumors of the pituitary intermediate lobe, which are extremely rare in humans. Thus, full assessment of Rb role in other, more relevant to human pathology, neoplasms is complicated. To prevent melanotroph neoplasia while preserving spontaneous carcinogenesis in other types of cells, we have prepared transgenic mice in which 770-bp fragment of pro-opiomelanocortin promoter directs expression of the human RB gene to melanotrophs (TgPOMC-RB). In three independent lines, transgenic mice crossed to Rb(+/-) background are devoid of melanotroph tumors but develop the usual spectrum of other neoplasms. Interestingly, abrogation of melanotroph carcinogenesis results in accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas. A combination of immunologic tests, cell culture studies, and tumorigenicity assays indicates that alpha-melanocyte-stimulating hormone, which is overproduced by melanotroph tumors, attenuates neoplastic progression by decreasing cell proliferation and inducing apoptosis. Taken together, we show that cell lineage-specific complementation of Rb function can be successfully used for refining available models of stochastic carcinogenesis and identify alpha-melanocyte-stimulating hormone as a potential attenuating factor during progression of neuroendocrine neoplasms.

Revision Functional Endoscopic Sinus Surgery.

Refractory chronic rhinosinusitis can be challenging to treat. Initial treatment focuses on medical and nonsurgical treatments. If these treatments fail, revision endoscopic sinus surgery is an option. A plan for revision surgery must address anatomic factors contributing to recurrence. Preoperative imaging and sinonasal endoscopy are systematically reviewed; areas of disease and "danger" zones are identified. Traditional anatomic landmarks are often obscured or absent; thus, a set of consistent landmarks (unchanged despite prior surgery) are used to navigate the revision endoscopic sinus surgery. Wide sinusotomies permit visualization and access to disease intraoperatively. Large sinus openings also facilitate post-operative debridements in clinic, endoscopic disease monitoring, and topical sinus therapy.