Impact of Obesity on Timing of Tracheotomy: A Multi-institutional Retrospective Study.

OBJECTIVE: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST). METHODS: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. RESULTS: Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m2) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%-75%]: 11.0 days [7-17 days] versus 9.0 days [5-14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%-75%]: 10.0 days [6-15 days] versus 10.0 days [6-15 days]; p = 0.36). CONCLUSION: BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

Chalk Talks for the Clinical Setting: Evaluation of a Medical Education Workshop for Fellows.

Introduction: Chalk talks are effective teaching tools in the clinical setting. However, data on optimal strategies for teaching medical educators how to develop and deliver them are limited. We designed and implemented two 50-minute workshops to help subspecialty fellows across GME create and deliver a chalk talk. Methods: The first workshop comprised a demonstration of an effective chalk talk and a discussion of best practices for creating chalk talks; the second was a practice session where fellows presented their chalk talks and received feedback from faculty and peers. We evaluated pre- and postworkshop confidence in the ability to create and deliver a chalk talk and develop learning objectives. Secondary outcomes were faculty and peer evaluations of the chalk talks. Results: Eighteen of 33 participants (54% response rate) completed both pre- and postsession surveys. Fellows reported improved confidence in their ability to create a chalk talk (22% vs. 83%, p < .001), deliver a chalk talk (17% vs. 83%, p < .001), and develop well-written learning objectives (11% vs. 83%, p < .001). After the workshop, participants were more likely to correctly identify a chalk talk that made use of an advanced organizer (67% vs. 89%, p < .05). Thirty-eight faculty and peers completed feedback evaluations of participants' chalk talks; most rated fellows' chalk talks highly in domains of content, delivery, design, learning objectives, and engagement. Discussion: The incorporation of these workshop within a course on medical education can effectively develop clinical teaching skills among subspecialty fellows in GME.

Transoral Surgery in HPV-Positive Oropharyngeal Carcinoma: Oncologic Outcomes in the Veterans Affairs System.

OBJECTIVES: Most transoral robotic surgery (TORS) literature for HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPC) derives from high-volume tertiary-care centers. This study aims to describe long-term recurrence and survival outcomes among Veterans Health Administration patients. MATERIALS AND METHODS: Using the US Veterans Affairs database, we identified patients with HPV-OPC treated with TORS between January 2010 and December 2016. Patients were stratified in risk categories: low (0-1 metastatic nodes, negative margins), intermediate (close margins, 2-4 metastatic nodes, lymphovascular or perineural invasion, pT3-pT4 tumor), or high (positive margins, extranodal extension (ENE), and/or ≥5 metastatic nodes). Primary outcomes included overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). RESULTS: The cohort included 161 patients of which 29 (18%) were low-risk, 45 (28%) intermediate-risk, and 87 (54%) high-risk. ENE was present in 41% of node-positive cases and 24% had positive margins. Median follow-up was 5.6 years (95% CI, 3.0-9.3). The 5-year DSS for low, intermediate, and high-risk groups were: 100%, 90.0% (95% CI, 75.4-96.1%), and 88.7% (95% CI, 78.3-94.2%). Pathologic features associated with poor DSS on univariable analysis included pT3-T4 tumors (HR 3.81, 95% CI, 1.31-11; p = 0.01), ≥5 metastatic nodes (HR 3.41, 95% CI, 1.20-11; p = 0.02), and ENE (HR 3.53, 95% CI, 1.06-12; p = 0.04). Higher 5-year cumulative incidences of recurrence were observed in more advanced tumors (pT3-T4, 33% [95% CI, 14-54%] versus pT1-T2, 13% [95% CI, 8-19%]; p = 0.01). CONCLUSIONS: In this nationwide study, patients with HPV-OPC treated with TORS followed by adjuvant therapy at Veterans Affairs Medical Centers demonstrated favorable survival outcomes comparable to those reported in high-volume academic centers and clinical trials. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:207-214, 2024.

Changes in the Parameters of Visual Evoked Potentials in Media Opacities.

Purpose: This study compared flash visual evoked potentials (VEPs) parameter differences between eyes with unilateral opaque media and their normal contralateral counterparts. Patients and Methods: We included 178 patients with unilateral media opacity and normal contralateral eye in each patient. The diseased eyes had normal ultrasonographic findings and were candidates for keratoplasty or anterior segment reconstruction. The patients underwent electrophysiological testing by the flash VEPs recording with the use of 1.4Hz (transient) and 8Hz (flicker) frequencies. Results: The medians of P2 implicit times were significantly higher in eyes with media opacity than in normal eyes, with median differences between both eyes of -6.7 ms. Furthermore, the median N2P2 amplitude was 9.70 µv with media opacity compared with 11.00 µv in the normal eyes, with a significant difference of 1.3 (p = 0.002). The flash VEPs median parameters recorded at a frequency of 8-Hz showed significant differences in medians of spectral plots of 0.6 µv between normal and abnormal eyes. The same for the signal-to-noise ratio, where the difference in medians was 3 dB. Analysis of the difference between both eyes (normal-abnormal) in each patient showed in P2 implicit time a difference range of -49 to 54.7 ms with a median difference of -3 ms. The difference in amplitudes of recorded N2P2 showed a median of 2.13 µv. There was a statistically significant but weak negative correlation between N2P2 amplitude (r spearman = -0.173, p = 0.021) and the grades of corneal opacity. Conclusion: Preoperative flash VEPs recording is useful for evaluating visual function in patients with unilateral media opacity to determine the future benefits of keratoplasty or anterior segment reconstruction. There are no correlations between the flash VEP parameters or the difference between the 2 eyes and the grades of corneal opacity.

Simulation-based workshop for emergency preparedness in otolaryngology.

Objectives: This study aimed to evaluate the outcomes of a hands-on simulation-based course with emphasis on procedural techniques, clinical reasoning, and communication skills developed to improve junior Otolaryngology - Head and Neck Surgery (OHNS) residents' preparedness in managing otolaryngologic emergencies. Methods: Junior OHNS residents and faculty from residency programs in California, Nevada, and Arizona participated in this workshop in 2020 and 2021. The stations featured airway management techniques, ultrasound-guided needle aspiration, nasoseptal hematoma evacuation, and facial fracture repair using various models and cadavers. Participants completed a pre-workshop survey, post-workshop survey, and 2-month follow-up survey that assessed resident anxiety and confidence in three OHNS emergency situations across knowledge, manual skills, and teamwork using a 5-point Likert scale. Results: Pre-workshop surveys reported the least anxiety and most confidence in teamwork, but the most anxiety and least confidence in technical skills and knowledge related to foreign body retrieval and airway management. Immediately post-workshop participants reported significant reductions in anxiety and increases in confidence, largest in the manual skills domain, in foreign body retrieval (anxiety: -0.99, confidence: +0.95, p < .01) and airway management stations (anxiety: -0.68, confidence: +1.07, p < .01). Data collected for the epistaxis station showed decreasing confidence and increasing anxiety following the workshop. Conclusion: Our findings demonstrate the effectiveness of a workshop in preparing junior residents in potentially lifesaving otolaryngologic techniques that residents will encounter. Optimizing use of simulation centered training can inform the future of residency education, improving confidence and decreasing anxiety in residents responsible for the safety of patients. Level of Evidence: III.

Factors Associated With Otolaryngologists Performing Tracheotomy.

Importance: Tracheotomies are frequently performed by nonotolaryngology services. The factors that determine which specialty performs the procedure are not defined in the literature but may be influenced by tracheotomy approach (open vs percutaneous) and other clinicodemographic factors. Objective: To evaluate demographic and clinical characteristics associated with tracheotomies performed by otolaryngologists compared with other specialists and to differentiate those factors from factors associated with use of open vs percutaneous tracheotomy. Design, Setting, and Participants: This multicenter, retrospective cohort study included patients aged 18 years or older who underwent a tracheotomy for cardiopulmonary failure at 1 of 8 US academic institutions between January 1, 2013, and December 31, 2016. Data were analyzed from September 2022 to July 2023. Exposure: Tracheotomy. Main Outcomes and Measures: The primary outcome was factors associated with an otolaryngologist performing tracheotomy. The secondary outcome was factors associated with use of the open tracheotomy technique. Results: A total of 2929 patients (mean [SD] age, 57.2 [17.2] years; 1751 [59.8%] male) who received a tracheotomy for cardiopulmonary failure (652 [22.3%] performed by otolaryngologists and 2277 [77.7%] by another service) were analyzed. Although 1664 of all tracheotomies (56.8%) were performed by an open approach, only 602 open tracheotomies (36.2%) were performed by otolaryngologists. Most tracheotomies performed by otolaryngologists (602 of 652 [92.3%]) used the open technique. Multivariable regression analysis revealed that self-reported Black race (odds ratio [OR], 1.89; 95% CI, 1.52-2.35), history of neck surgery (OR, 2.71; 95% CI, 2.06-3.57), antiplatelet and/or anticoagulation therapy (OR, 1.74; 95% CI, 1.29-2.36), and morbid obesity (OR, 1.54; 95% CI, 1.24-1.92) were associated with greater odds of an otolaryngologist performing tracheotomy. In contrast, history of neck surgery (OR, 1.36; 95% CI, 0.96-1.92), antiplatelet and/or anticoagulation therapy (OR, 0.80; 95% CI, 0.56-1.14), and morbid obesity (OR, 0.94; 95% CI, 0.74-1.19) were not associated with undergoing open tracheotomy when performed by any service, and Black race (OR, 0.56; 95% CI, 0.44-0.71) was associated with lesser odds of an open approach being used. Age-adjusted Charlson Comorbidity Index score greater than 4 was associated with greater odds of both an otolaryngologist performing tracheotomy (OR, 1.26; 95% CI, 1.03-1.53) and use of the open tracheotomy technique (OR, 1.48, 95% CI, 1.21-1.82). Conclusions and Relevance: In this study, otolaryngologists were significantly more likely than other specialists to perform a tracheotomy for patients with history of neck surgery, morbid obesity, and ongoing anticoagulation therapy. These findings suggest that patients undergoing tracheotomy performed by an otolaryngologist are more likely to present with complex and challenging clinical characteristics.

Age-Related Differences in Oncological Outcomes in Renal Cell Carcinoma: Impact of Functional Conservation as Measured by Postoperative eGFR.

INTRODUCTION: We sought to determine whether loss of renal function increases risk of recurrence and metastases in renal cell carcinoma (RCC), and whether this impact was age-related. MATERIALS AND METHODS: We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry. Patients were separated into younger (<65 years old) and elder (≥65 years old) age groups, and rates of de novo estimated glomerular filtration rate (eGFR<45 mL/min/1.73m2 [eGFR<45]) were calculated. Multivariable analysis (MVA) was conducted for predictors of progression-free survival (PFS) and all-cause mortality (ACM). Kaplan-Meier Analysis (KMA) was conducted for PFS and overall survival (OS) in younger and elder age groups stratified by functional status. RESULTS: We analyzed 1805 patients (1113 age<65, 692 age≥65). On MVA in patients <65, de novo eGFR<45 was independently associated with greater risk for worsened progression (HR=1.61, P=.038) and ACM (HR=1.82, P=.018). For patients ≥65, de novo eGFR<45 was not independently associated with progression (P=.736), or ACM (P=.286). Comparing patients with de novo eGFR<45 vs. eGFR ≥45, KMA demonstrated worsened 5-year PFS and OS in patients <65 (PFS: 68% vs. 86%, P<.001; OS: 73% vs. 90%, P<.001), while in patients ≥65, only 5-year OS was worsened (77% vs. 81%, P<.021). CONCLUSION: Development of de novo eGFR<45 was associated with more profound impact on patients <65 compared to patients ≥65, being an independent risk factor for PFS and ACM. The mechanisms of this phenomenon are unclear but underscore desirability for nephron preservation when safe and feasible in younger patients.

Adjuvant Radiotherapy in Surgically Treated HPV-Positive Oropharyngeal Carcinoma with Adverse Pathological Features.

Purpose: HPV-positive oropharyngeal carcinoma (HPV-OPC) is increasingly treated with primary surgery. The National Comprehensive Cancer Network (NCCN) recommends adjuvant therapy for surgically treated HPV-OPC displaying adverse pathological features (AF). We evaluated adjuvant radiotherapy patterns and outcomes in surgically treated AF-positive HPV-OPC (AF-HPV-OPC). Methods: The National Cancer Database was interrogated for patients ≥ 18 years with early-stage HPV-OPC from 2010 to 2017 who underwent definitive resection. Patients that had an NCCN-defined AF indication for adjuvant radiotherapy were assessed, including positive surgical margins (PSM), extranodal extension (ENE), lymphovascular invasion, and level 4/5 cervical lymph nodes. Overall survival (OS) was evaluated using Cox proportional hazards models and Kaplan−Meier analysis in whole and propensity score matched (PM) cohorts. Results: Of 15,036 patients meeting inclusion criteria, 55.7% were positive for at least one AF. Presence of any AF was associated with worse OS (hazard ratio (HR) = 1.56, p < 0.001). In isolation, each AF was associated with worse OS. On PM analysis, insurance status, T2 category, Charlson-Deyo comorbidity score, ENE (HR = 1.81, p < 0.001), and PSM (HR = 1.58, p = 0.002) were associated with worse OS. Median 3-year OS was 92.0% among AF-HPV-OPC patients undergoing adjuvant radiotherapy and 84.2% for those who did not receive adjuvant radiotherapy (p < 0.001, n = 1678). The overall rate of patients with AF-HPV-OPC who did not receive adjuvant radiotherapy was 13% and increased from 10% in 2010 to 17% in 2017 (ptrend = 0.007). Conclusions: In patients with AF-HPV-OPC, adjuvant radiotherapy is associated with improved survival. In the era of de-escalation therapy for HPV-OPC, our findings demonstrate the persistent prognostic benefit of post-operative radiotherapy in the setting of commonly identified adverse features. Ongoing clinical trials will better elucidate optimized patient selection for de-escalated therapy.

Tailored order set in the electronic health record decreases postoperative opioid prescriptions.

BACKGROUND: Adherence to opioid prescribing protocols after operations remains challenging despite published guidelines. Integration of these guidelines with the electronic health record could potentially improve their adoption. We hypothesize that implementing an electronic health record order set containing prepopulated tablet quantities tailored to surgical procedures based on published guidelines will decrease postoperative opioid prescription. METHODS: We conducted a 12-month prepost intervention study on adult patients who underwent appendectomy, cholecystectomy, inguinal or umbilical hernia repair, thyroidectomy, or parathyroidectomy at a single institution. An electronic health record order set was developed with prepopulated opioid tablet quantities reflecting the upper limit of published recommendations. The primary endpoint was change in morphine milligram equivalent prescribed postintervention and was analyzed using linear regression adjusting for age, race, procedure, and prescriber training level. Secondary endpoints were emergency department visits for pain-related issues and opioid refill rates. RESULTS: We identified 524 patients (mean age = 53, 51% male) in our baseline cohort and 433 patients (mean age = 52, 58% male) in our postintervention group. The mean morphine milligram equivalent prescribed was 62.6 and 50.4 for the preintervention and postintervention cohorts, respectively (P = .049). Thyroidectomies and parathyroidectomies achieved the largest decrease after intervention, which decreased to 42.6 morphine milligram equivalent from 79.7 morphine milligram equivalent preintervention (P < .001). Refill rate was 1.6% postintervention compared to 3.1% preintervention (P = .20), and emergency department visit for pain control rate was 0.2% post intervention and 2.5% preintervention (P = .005). CONCLUSION: An electronic health record tailored order set based on prescription guidelines is a safe, effective, and scalable intervention for decreasing opioid prescriptions after operations.

Outcomes of Lymph Node Dissection in Nephroureterectomy in the Treatment of Upper Tract Urothelial Carcinoma: Analysis of the ROBUUST Registry.

PURPOSE: We sought to evaluate outcomes of lymph node dissection (LND) in patients with upper tract urothelial carcinoma. MATERIALS AND METHODS: We performed a multicenter retrospective analysis utilizing the ROBUUST (for RObotic surgery for Upper Tract Urothelial Cancer Study) registry for patients who did not undergo LND (pNx), LND with negative lymph nodes (pN0) and LND with positive nodes (pN+). Primary and secondary outcomes were overall survival (OS) and recurrence-free survival (RFS). Multivariable analyses evaluated predictors of outcomes and pathological node positivity. Kaplan-Meier analyses (KMAs) compared survival outcomes. RESULTS: A total of 877 patients were analyzed (LND performed in 358 [40.8%]/pN+ in 73 [8.3%]). Median nodes obtained were 10.2 for pN+ and 9.8 for pN0. Multivariable analyses noted increasing age (OR 1.1, p <0.001), pN+ (OR 3.1, p <0.001) and pathological stage pTis/3/4 (OR 3.4, p <0.001) as predictors for all-cause mortality. Clinical high-grade tumors (OR 11.74, p=0.015) and increasing tumor size (OR 1.14, p=0.001) were predictive for lymph node positivity. KMAs for pNx, pN0 and pN+ demonstrated 2-year OS of 80%, 86% and 42% (p <0.001) and 2-year RFS of 53%, 61% and 35% (p <0.001), respectively. KMAs comparing pNx, pN0 ≥10 nodes and pN0 <10 nodes showed no significant difference in 2-year OS (82% vs 85% vs 84%, p=0.6) but elicited significantly higher 2-year RFS in the pN0 ≥10 group (60% vs 74% vs 54%, p=0.043). CONCLUSIONS: LND during nephroureterectomy in patients with positive lymph nodes provides prognostic data, but is not associated with improved OS. LND yields ≥10 in patients with clinical node negative disease were associated with improved RFS. In high-grade and large tumors, lymphadenectomy should be considered.

Disparities in Telemedicine Utilization for Urology Patients During the COVID-19 Pandemic.

OBJECTIVE: To determine the odds of accessing telemedicine either by phone or by video during the COVID-19 pandemic. METHODS: We performed a retrospective study of patients who were seen at a single academic institution for a urologic condition between March 15, 2020 and September 30, 2020. The primary outcome was to determine characteristics associated with participating in a telemedicine appointment (video or telephone) using logistic regression multivariable analysis. We used a backward model selection and variables that were least significant were removed. We adjusted for reason for visit, patient characteristics such as age, sex, ethnicity, race, reason for visit, preferred language, and insurance. Variables that were not significant that were removed from our final model included median income estimated by zip code, clinic location, provider age, provider sex, and provider training. RESULTS: We reviewed 4234 visits: 1567 (37%) were telemedicine in the form of video 1402 (33.1%) or telephone 164 (3.8%). The cohort consisted of 2516 patients, Non-Hispanic White (n = 1789, 71.1%) and Hispanic (n = 417, 16.6%). We performed multivariable logistic regression analysis and demonstrated that patients who were Hispanic, older, or had Medicaid insurance were significantly less likely to access telemedicine during the pandemic. We did not identify differences in telemedicine utilization when stratifying providers by their age, sex, or training type (physician or advanced practice provider). CONCLUSION: We conclude that there are differences in the use of telemedicine and that this difference may compound existing disparities in care. Additionally, we identified that these differences were not associated with provider attributes. Further study is needed to overcome barriers in access to telemedicine.

Evaluation of the association of health care system access with kidney cancer surgical outcomes for hispanic and non-hispanic white patients.

OBJECTIVE: To determine the impact of health care system access on outcomes for Hispanic and Non-Hispanic White patients with renal cell carcinoma (RCC). METHODS: We retrospectively analyzed Hispanic and non-Hispanic White patients diagnosed with localized RCC between 2007 and 2020. We used Health Resources and Services Administration criteria to identify patients living in Medically Underserved Areas (MUA). Primary outcome all-cause mortality and cancer-specific survival using Log Rank test on Kaplan Meier Analysis. Secondary outcome was all-cause mortality and cancer specific survival on Cox Regression when adjusting for risk factors. RESULTS: We analyzed 774 patients, 246 (31.8%) Hispanic patients and 528 (68.2%) Non-Hispanic White patients. Hispanic ethnicity was associated with lower risk of ACM (HR 0.53, P = 0.019) and there was no difference for cancer specific survival (HR 0.57, P = 0.059). Living in a MUA was associated with worse all-cause mortality (P = 0.010) but not cancer specific survival (CSS) (P = 0.169). Comparing Hispanic and Non-Hispanic Whites, KMA revealed no difference in 5-year all-cause mortality (83.1% vs. 78.8%, P = 0.254) and 5-year CSS (85.7% vs. 85.4%, P = 0.403). CONCLUSIONS: Hispanics had lower all-cause mortality risk and no significant differences in 5-year overall survival and CSS compared to non-Hispanic Whites. Our findings indicate that tertiary referral centers may help mitigate inequalities in access to care.

Evaluation of Insurance Coverage and Cancer Stage at Diagnosis Among Low-Income Adults With Renal Cell Carcinoma After Passage of the Patient Protection and Affordable Care Act.

Importance: The association of the Patient Protection and Affordable Care Act (ACA) with insurance status and cancer stage at diagnosis among patients with renal cell carcinoma (RCC) is unknown. Objective: To test the hypothesis that the ACA may be associated with increased access to care through expansion of insurance, which may vary based on income. Design, Setting, and Participants: This retrospective cohort analysis included patients diagnosed with RCC from January 1, 2010, to December 31, 2016, in the National Cancer Database. Data were analyzed from July 1 to December 31, 2020. The periods from 2010 to 2013 and from 2014 to 2016 were defined as pre- and post-ACA implementation, respectively. Patients were categorized as living in a Medicaid expansion state or not. Exposures: Implementation of the ACA. Main Outcomes and Measures: The absolute percentage change (APC) of insurance coverage was calculated before and after ACA implementation in expansion and nonexpansion states. Secondary outcomes included change in stage at diagnosis, difference in the rate of insurance change, and change in localized disease between expansion and nonexpansion states. Adjusted difference-in-difference modeling was performed. Results: The cohort included 78 099 patients (64.7% male and 35.3% female; mean [SD] age, 54.66 [6.46] years), of whom 21.2% had low, 46.2% had middle, and 32.6% had high incomes. After ACA implementation, expansion states had a lower proportion of uninsured patients (adjusted difference-in-difference, -1.14% [95% CI, -1.98% to -1.41%]; P = .005). This occurred to the greatest degree among low-income patients through the acquisition of Medicaid (APC, 11.0% [95% CI, 8.6%-13.3%]; P < .001). Implementation of the ACA was also associated with an increase in detection of stage I and II disease (APC, 4.0% [95% CI, 1.6%-6.3%]; P = .001) among low-income patients in expansion states. Conclusions and Relevance: Among patients with RCC, ACA implementation was associated with an increase in insurance coverage status in both expansion and nonexpansion states for all income groups, but to a greater degree in expansion states. The proportion of patients with localized disease increased among low-income patients in both states. These data suggest that ACA implementation is associated with earlier RCC detection among lower-income patients.

Management of Persistent Corneal Epithelial Defects with Human Amniotic Membrane-derived Dry Matrix.

OBJECTIVE: To report the outcomes of using human amniotic membrane-derived dry matrix (AMDDM) in the management of persistent corneal epithelial defects (PEDs) of various etiologies. METHODS: A cohort study of 84 patients age range 7 to 92 years with 93 PEDs were treated with AMDDM (Omnigen® using OmniLenz® at two centers (Queen Victoria Hospital and Maidstone Hospital) in the UK. The main outcome measures were healing response of PED and time to heal after application of AMDDM. RESULTS: A total of 106 applications of AMDDM were recorded for 81 patients (52 males, 29 females) with a spectrum of different etiologies. Fifty-eight percent of the eyes showed complete healing, and 28% showed partial decrease of the size of PEDs with average treatment length recorded as 22.4±12.3 days. In patients with limbal stem cell deficiency (n=44; aniridia=12, chemical injury=9, Stevens-Johnson syndrome=10), 50% of PEDs showed complete healing and 27% showed partial healing. In patients with microbial keratitis (n=21) (bacterial: 13, fungal: 4, herpetic: 3, acanthamoeba: 1) 57% of PEDs showed complete healing and 33% were partially healed. In patients with keratoplasty (n=16), 56% of PEDs showed complete healing and 31% were partially healed. Vision remained stable in 59% and improved in 27% of the study the population. CONCLUSION: AMDDM can be easily applied in the clinical setting and has demonstrated its efficiency as a new tool to treat persistent epithelial defects.

Incidence and Risk Factors of Ocular Hypertension/Glaucoma After Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To evaluate the incidence, demographics, associated risk factors, management and clinical outcomes of ocular hypertension/glaucoma after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: A cohort review of 81 DSAEK cases was performed at Queen Victoria Hospital, United Kingdom. Patients with pre-existing glaucoma, transient increased IOP within the first 48 hours post-graft, additional post-transplant surgery, or failed to complete one year follow-up were excluded from the study. Ocular hypertension was defined as intraocular pressure (IOP) elevation >21mmHg or ≥6mmHg from baseline at any postoperative visit. The study looked at the incidence, risk factors, response to anti-glaucoma treatment, graft failure and best corrected visual acuity. RESULTS: The incidence of post-DSAEK ocular hypertension and glaucoma was 51.9% and 13.6%, respectively. Steroid-induced IOP elevation was the most frequent cause, with an incidence of 38.3%. Risk factors such as pseudophakia (p=0.024) and preoperative IOP>16 (p=0.003) were found to be associated with post-DSAEK ocular hypertension. Preoperative IOP>16 had 5.27 times risk of IOP elevation. Eyes with graft dislocation and/or detachment were significantly associated with post-DSAEK glaucoma (p=0.038). There was no negative effect of OHT on visual acuity and graft status. CONCLUSION: Glaucoma and OHT are common postoperative complications of DSAEK. Although steroid-induced IOP elevation was the most frequent cause, there are other reasons associated with development of post-DSAEK glaucoma, including graft dislocation and detachment. Eyes with preoperative IOP>16 mm Hg may require a close monitoring of IOP. In addition, management by medical treatment results in good visual acuity and graft clarity.

Astrocytes propel neurovascular dysfunction during cerebral cavernous malformation lesion formation.

Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in 1 of 3 genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2- and KLF4-dependent elevation of eNOS in CCM endothelium. The increased brain endothelial production of NO stabilized HIF-1α in astrocytes, resulting in increased VEGF production and expression of a "hypoxic" program under normoxic conditions. We showed that the upregulation of cyclooxygenase-2 (COX-2), a direct HIF-1α target gene and a known component of the hypoxic program, contributed to the development of CCM lesions because the administration of a COX-2 inhibitor significantly prevented the progression of CCM lesions. Thus, non-cell-autonomous crosstalk between CCM endothelium and astrocytes propels vascular lesion development, and components of the hypoxic program represent potential therapeutic targets for CCMs.

Bladder outlet obstruction secondary to Brunn's cyst: A rare presentation in young man.

Bladder outlet obstruction in younger men is usually secondary to urethral stricture disease. In the elderly, it is often a due to benign prostatic hyperplasia (BPH). Bladder obstruction secondary to Brunn's Cyst should be considered as a differential diagnosis in young men with acute onset of obstructive symptoms and a cystic lesion at the bladder neck. We report a case of bladder outlet obstruction secondary to Brunn's cyst in a 21-year-old male. Radiological investigations, cystoscopy, and histological examination revealed the rare pathology, which was managed by endoscopic de-roofing of the cyst. The symptoms resolved dramatically, with no recurrence.

Utilization of renal mass biopsy in patients with localized renal cell carcinoma: A population-based study utilizing the National Cancer Database.

OBJECTIVE: To evaluate trends and factors predicting use of renal mass biopsy (RMB) for localized Renal Cell Carcinoma in the United States (US) in the context of current guidelines recommendations. METHODS: We queried the National Cancer Database for cT1-cT3N0M0 Renal Cell Carcinoma diagnosed between 2004 and 2015. Temporal trends of RMB were characterized based on tumor size, treatment (partial nephrectomy [PN], radical nephrectomy [RN], ablation, and no treatment), age and Charlson Comorbidity Index with slopes compared using analysis of variance. Multivariable analysis was used to determine factors associated with use of RMB. RESULTS: Of 338,252 patients analyzed, 11.9% (40,276) underwent RMB. Use of RMB increased throughout the study period from 1,586 (7.6%) in 2004 to 5,629 (16.2%) in 2015 (P < 0.001). Use of RMB increased greatest for ablation (27 to 63%, P < 0.001) and tumors 2-4 cm (9 to 20%, P < 0.001). Multivariable analysis showed year of diagnosis (OR = 1.06; P < 0.001), higher education (OR = 1.09; P < 0.001) and insured status (OR = 1.23; P < 0.001) were associated with increased RMB. Compared to tumors ≤2 cm, tumors 2.1-4 cm (OR = 1.36; P=<0.001), 4.1-7 cm (OR = 1.18; P <0.001) and >7 cm (OR = 1.05; P = 0.03) were associated with higher rates of RMB. Compared to RN, PN was not associated with increased RMB (OR = 1.00; P = 0.92), while ablation (OR = 10.90; P < 0.001) and no surgical treatment (OR = 4.83; P < 0.001) were. CONCLUSION: RMB utilization increased overall, with largest increase associated with ablation. Nonetheless, only two-thirds of patients underwent RMB with ablation, suggesting persistent underutilization. Rates of RMB for tumors ≤2 cm and in those undergoing no treatment increased less, suggesting less utilization for surveillance. However, rates for tumors >2-4 cm increased more, suggesting selective utilization of RMB to guide decision-making and risk stratification in small renal masses.

Isolation and Purification of Mouse Brain Endothelial Cells to Study Cerebral Cavernous Malformation Disease.

We describe a method to purify primary brain microvascular endothelial cells (BMEC) from mice bearing floxed alleles of Krit1 (Krit1fl/fl) or Pdcd10 (Pdcd10fl/fl) and an endothelial-specific tamoxifen-regulated Cre recombinase (Pdgfb-iCreERT2), and used these to delete Krit1 or Pdcd10 genes in a time-controlled manner. These BMEC culture models contain a high degree of purity and have been used to identify the major molecular processes involved in loss of Krit1/Pdcd10-induced altered brain endothelial phenotype and function. In addition, these in vitro models of cerebral cavernous malformations (CCMs) enable molecular, biochemical, and pharmacological studies that have contributed significantly to understand the pathogenesis of CCMs. The findings using this in vitro CCMs model have been validated in mouse CCM models and observed in human CCMs. In this chapter, we summarize procedures for isolation and purification of BMEC from transgenic mice, as well as our experience to genetically inactivate CCM genes in the brain endothelium.

Contemporary Management of Renal Transplant Recipients With De Novo Urolithiasis: A Single Institution Experience and Review of the Literature.

OBJECTIVES: We report on the long-term follow-up of managing allograft stones at a single tertiary referral institution and review the relevant literature. MATERIALS AND METHODS: A retrospective analysis of renal allograft recipient charts was performed to identify patients who developed allograft lithiasis between 1974 and 2009. Patient and stone characteristics, diagnoses, treatments, and outcomes were described. RESULTS: Sixteen patients developed 22 stones after a median follow-up of 170 months (range, 51-351 mo). The mean (standard deviation) and median diameter of the stones were 13.8 (8.5) mm and 11 mm. Among these, 3 stones were treated conservatively, 3 by shock-wave lithotripsy, and 7 by cystolitholapaxy. Seven patients underwent percutaneous treatment in the form of percutaneous nephrostomy tube fixation and spontaneous passage of stone (1 stone), shock-wave lithotripsy (1 stone), antegrade stenting (1 stone), and percutaneous nephrolithotomy (6 stones). All patients were stone free after treatment, except for 2 patients whose stones were stable and peripheral on long-term follow-up. CONCLUSIONS: Allograft lithiasis requires a multimodal treatment tailored according to stone and graft characteristics. Protocols regarding spontaneous passage can be adopted if there is no harm to the graft and the patient is compliant. Careful attention to the anatomy during percutaneous nephrostomy tube placement is mandatory to avoid intestinal loop injury. A more attentive follow-up is required for early stone management.