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Background: There is persistent controversy surrounding the merit of surgical volume benchmarks being used solely as a sufficient proxy for assessing the quality of open abdominal aortic aneurysm (AAA) repair. Importantly, operative volume quotas may fail to reflect a more nuanced and comprehensive depiction of surgical outcomes most relevant to patients. Accordingly, we herein propose a patient-centered textbook outcome (TO) for AAA repair that is analogous to other large magnitude extirpative operations performed in other surgical specialties, and test its feasibility to discriminate hospital performance using Society for Vascular Surgery (SVS) volume guidelines., Methods: All elective open infrarenal AAA repairs (OAR) in the SVS-Vascular Quality Initiative were examined (2009-2022). The primary end point was a TO, defined as a composite of no in-hospital complication or reintervention/reoperation, length of stay of ≤10 days, home discharge, and 1-year survival rates. The discriminatory ability of the TO measure was assessed by comparing centers that did or did not meet the SVS annual OAR volume threshold recommendation (high volume ≥10 OARs/year; low volume <10 OARs/year). Logistic regression and multivariable models adjusted for patient and procedure-related differences., Results: A total of 9657 OARs across 198 centers were analyzed (mean age, 69.5 ± 8.4 years; female, 26%; non-White, 12%). A TO was identified in 44% (n = 4293) of the overall cohort. The incidence of individual TO components included no in-hospital complication (61%), no in-hospital reintervention or reoperation (92%), length of stay of ≤10 days (78%), home discharge (76%), and 1-year survival (91%). Median annual center volume was 6 (interquartile range, 3-10) and a majority of centers did not meet the SVS volume suggested threshold (<10 OARs/year, n = 148 [74%]). However, most patients (6265 of 9657 [65%]) underwent OAR in high-volume hospitals. When comparing high- and low-volume centers, a TO was more likely to occur in high-volume institutions: ≥10 OARs/year (46%) vs <10 OARs/year (42%; P = .0006). The association of a protective effect for higher center volume remained after risk adjustment (odds ratio, 1.1; 95% confidence interval, 1.05-1.26; P = .003)., Conclusions: TOs for elective OAR reflect a more nuanced and comprehensive patient centered proxy to measure care delivery, consistent with other surgical specialties. Surprisingly, a TO was achieved in <50% of elective AAA cases nationally. Although the likelihood of a TO seems to correlate with SVS center volume recommendations, it more importantly reflects elements which may be prioritized by patients and thus offers insights into further improving real-world AAA care., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Vascular complications (VCs) associated with extracorporeal membrane oxygenation (ECMO) during index hospitalization are prevalent and associated with increased mortality. Few studies have evaluated late VCs following ECMO; this study aims to assess occurrence and management practices of late VCs following discharge., Methods: A retrospective single-institution review was performed of all patients surviving initial hospitalization after being cannulated for central or peripheral veno-venous (VV) or veno-arterial (VA) ECMO between January 1, 2019, and December 31, 2020. Primary outcomes were to categorize and determine the rate of late VCs. Late VCs were defined as any cannulated vessel injury resulting from ECMO cannulation presenting after discharge from index hospitalization. Analysis was conducted by cannulated vessel and stratified by VV or VA ECMO configurations., Results: A total of 229 patients were identified, of which 50.6% (n = 116) survived until discharge. Late VCs occurred in 7.8% of the surviving cohort (n = 9/116); with a median time until presentation of 150 days (interquartile range, 83-251 days). The most common late VC was infection (n = 5; 55.6%) followed by progression to limb-threatening ischemia (n = 4; 44.4%). Urgent procedures were required in 55.6% of patients (n = 5), whereas 44.4% (n = 4) were elective interventions. Interventions performed for management of late VCs included lower extremity arterial revascularization (n = 6; 66.7%), major (n = 1; 11.1%) or minor amputation (n = 1; 11.1%), and wound debridement (n = 1; 11.1%). The majority of patients presenting with late VCs had initially been cannulated for peripheral VA ECMO (n = 8; 88.9%), and one patient (11.1%) was cannulated for peripheral VV ECMO. VCs during index hospitalization were seen in 77.8% of patients (n = 7) returning with late VCs. Odds for late VCs were significantly increased in patients that had been cannulated for ECMO as part of extracorporeal cardiopulmonary resuscitation (odds ratio, 8.4; P = .016) and in cases where patients had experienced an index VC during index hospitalization (odds ratio, 19.3; P = .001)., Conclusions: Late vascular complications after peripheral ECMO cannulation are not rare, particularly after arterial cannulation. Patients should be followed closely early after surviving ECMO with wound evaluation and formal assessment of perfusion with ankle-branchial indices in the cannulated limb., Competing Interests: Disclosures A.W.B. reports consulting for Artivion, Cook Medical, Medtronic, Philips, and Terumo Aortic; and research support from Cook Medical, Medtronic, Philips, Terumo Aortic, W.L. Gore & Associates (all proceeds to the U. of Alabama at Birmingham)., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Early survival (1-year) after elective repair of complex abdominal aortic aneurysms (AAA) or thoracoabdominal aortic aneurysms (TAAA) can be used as an indicator of successful repair and provides a reasonable countermeasure to the annual rupture risk based on diameter. We aimed to identify preoperative factors associated with 1-year mortality after fenestrated or branched endovascular aortic repair (F/BEVAR) and develop a predictive model for 1-year mortality based on patient-specific risk profiles., Methods: The US-Aortic Research Consortium database was queried for all patients undergoing elective F/BEVAR for complex AAA (cAAA) or TAAA from 2005 to 2022. The primary outcome was 1-year survival based on preoperative risk profile. Multivariable Cox regression was used to determine preoperative variables associated with 1-year mortality overall and by extent of aortic pathology. Logistic regression was performed to build a predictive model for 1-year mortality based on number of risk factors present., Results: A total of 2099 patients met the inclusion criteria for this study (cAAA: n = 709 [34.3%]; type 1-3 TAAA: n = 777 [37.6%]; type 4-5 TAAA: n = 580 [28.1%]). Multivariable Cox regression identified the following significant risk factors associated with 1-year mortality: current smoker, chronic obstructive pulmonary disease, congestive heart failure (CHF), aortic diameter >7 cm, age >75 years, extent 1-3, creatinine >1.7 mg/dL, and hematocrit <36%. When stratified by extent of aortic involvement, multivariable Cox regression revealed risk factors for 1-year mortality in cAAA (CHF maximum aortic diameter >7 cm, hematocrit <36 mg/dL, and current smoking status), type 1-3 TAAA (chronic obstructive pulmonary disease, CHF, and age >75 years), and type 4-5 TAAA (age >75 years, creatinine >1.7 mg/dL, and hematocrit <36 mg/dL). Logistic regression was then used to develop a predictive model for 1-year mortality based on patient risk profile. Appraisal of the model revealed an area under the curve of 0.64 (P < .001), and an observed to expected ratio of 0.85., Conclusions: This study describes multiple risk factors associated with an increase in 1-year mortality after F/BEVAR. Given that elective repair of cAAA or TAAA is offered to some patients in whom future rupture risk outweighs operative risk, these findings suggest that highly comorbid patients with smaller aneurysms may not benefit from repair. Descriptive and predictive models for 1-year mortality based on patient risk profiles can serve as an adjunct in clinical decision-making when considering elective F/BEVAR., Competing Interests: Disclosures A.W.B. is a consultant for Artivion, Cook Medical, Medtronic, Philips, and Terumo Aortic and received research support from Cook Medical, Medtronic, Philips, Terumo Aortic, and W. L. Gore & Associates, with all proceeds to the University of Alabama at Birmingham. A.S. is a consultant for Artivion, Cook Medical, and Philips and received research support from Cook Medical and Philips, with all proceeds to the UMass Memorial Foundation. D.S. is a consultant for Cook, W. L. Gore & Associated, Medtronic, and Phillips; receives research support from Cook, Phillips, and W. L. Gore & Associates; and is a member of the scientific advisory board for W. L. Gore & Associates. M.F. is a consultant for Cook, W. L. Gore & Associates, Getinge, ViTAA medical, and Centerline Biomedical; receives research support from W. L. Gore & Associates, Gore, and ViTAA medical; and has stock options with Centerline Biomedical. G.O. is a consultant for GE, Cook, W. L. Gore & Associates, and Centerline biomedical; receives research support from GE; and is a member of the scientific advisory board for Cook and Centerline Biomedical. The remaining authors report no conflicts. Cook Medical (Bloomington, IN) and Research support from US-Aortic Research Consortium. C.A.B. is funded by the VA Quality Scholars Program, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Investigate readmission rates, diagnoses associated with readmission, and associations with mortality through 90 days postoperatively after elective endovascular thoracic and thoracoabdominal aortic repair overall and by extent of coverage., Methods: A cohort of index elective nontraumatic endovascular thoracic and thoracoabdominal aortic cases from 2010 to 2018 was derived from the Vascular Implant Surveillance and Interventional Outcomes Network. Cohort readmissions within 90 days postoperative were examined both overall and by Crawford extent (CE) of aortic coverage. Postoperative mortality was examined by reason for readmission and CE., Results: The cohort consisted of 2,105 patients who underwent endovascular thoracic and thoracoabdominal aortic repair (1,550 CE 0A/0B; 242 CE 1-3; 313 CE 4-5). Cumulative risk for 90-day readmission was 34.3% in CE 0A/0B repairs, 33.4% in CE 4-5 repairs, and 47.4% in CE 1-3 repairs. Compared with CE 0A/B, patients with CE 1-3 repairs experienced an increased risk of readmission within 90 days postoperatively after adjusting for preoperative factors (adjusted hazard ratio [HR] 1.27 [1.00, 1.61]), while the readmission risk for CE 4-5 repairs did not differ significantly (adjusted HR 0.83 [0.64, 1.06]). Significant risk factors for 90-day readmission included chronic obstructive pulmonary disease, dialysis dependence, limited ambulation, visceral/spinal ischemia, and in-hospital stroke. Discharge to home was protective against readmission (HR 0.65, confidence interval 0.54-0.79). Patients with a readmission within 90 days had a 7.89-fold increase in 90-day mortality (HR 7.84; 5.17, 11.9) compared with those not readmitted., Conclusions: Increasing extent of endovascular thoracic and thoracoabdominal aortic repair was associated with higher 90-day readmission rates. Readmission for all CE was associated with near 8-fold increased risk of mortality. Risk factors associated with increased risk for readmission included pulmonary insufficiency, renal disease, and poor functional status. These findings can inform stakeholders about investment of resources to improve processes of care that both target prevention and mitigate risk of readmission after elective endovascular thoracic and thoracoabdominal aortic repair., (Copyright © 2024. Published by Elsevier Inc.)

Background: Veterans represent a distinct cultural group whose perceptions of illness and treatment are influenced by military culture. The study explores how prior military service shapes Veterans' assumptions and behaviors in the setting of aneurysm repair surgery., Study Design: We conducted content and thematic analysis of a case series of 10 transcripts from telephone interviews with older (76.7 ± 4.3 years) African American and White male Veterans now residing in the Southern U.S. who underwent open or endovascular aneurysm surgery at Veterans Affairs Medical Centers or university affiliates between 2004 and2019., Results: Throughout the continuum of care, Veterans described deferring to authority and not questioning provider's decisions [" I just can't make a judgment on that, because I'm not a doctor "]. Veterans valued commitment and articulated pride in keeping logistically challenging surveillance appointments [ I always took them very seriously. . . If I'm scheduled for something by the doctor, I always make it." ]. The routine structure of VA care aligned with Veterans military experiences, facilitating compliance with doctor's orders. However, procedural deviations in VA care were disconcerting for patients [" They haven't reached out to me in at least three years, since my surgery; I was being seen once a year and then all of a sudden, they just quit." ]. While Veterans praised VA care, they exhibited sensitivity to signs of untoward treatment from clinical and support staff "…my surgeon, he never talked to me before, nor after, no anytime…I thought that maybe that wasn't right"., Conclusions: Military culture embodies rank, order, and respect, and remains a source of strength and stability for Veterans in their medical care late in life. Cultural competency about how military service has shaped Veterans' expectations can enhance providers' awareness of patients' military mindsets and inform surgeons' efforts to engage Veterans in shared decision making., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: While there has been great interest in offering selective neurectomy (SN) to patients with nonflaccid facial palsy (NFFP), postoperative outcomes are inconsistent. Objective: To assess overall SN outcome in NFFP patients and to examine correlation between preoperative factors and SN outcome. Methods: SN cases were retrospectively identified between 2019 and 2021. Patient factors and facial function were assessed using chart review, the Facial Clinimetric Evaluation (FaCE), the electronic clinician-graded facial function tool (eFACE), and an automated computer-aided facial assessment tool (Emotrics). Correlations between preoperative factors and patients outcome were established. Results: Fifty-eight SN cases were performed; 88% were females, and median age was 53 years (range 11-81). Outcome assessment was 8 months on average (1-24 months). Postoperatively, multiple eFACE and Emotrics parameters improved significantly, including ocular, perioral, and synkinesis metrics. In preoperative factors assessment, age >50, facial palsy (FP) duration >2 years, poor preoperative facial function, and nontrauma etiology all correlated with greater improvements compared with younger patients, those with shorter duration facial palsy, trauma etiology, and better preoperative facial function. Conclusions: SN can significantly improve facial function; we have identified several preoperative factors that correlated to outcome.

Revascularization of complex pelvic vascular anatomy presents an ongoing clinical challenge when treating aortoiliac disease. As vascular surgeons continue to intervene upon increasingly complex aortoiliac pathology, the role of pelvic revascularization is important for the preservation of pelvic organ function and prevention of devastating spinal cord ischemia. In this study we describe the indications, techniques, and clinical outcomes of a novel hybrid pelvic revascularization repair that focuses on optimizing revascularization while limiting pelvic surgical dissection during the management of complex aortic pathology in patients physiologically or anatomically unsuitable for traditional pelvic revascularization techniques., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: While there is great interest in selective neurectomy (SN) for patients with synkinesis, outcomes can be inconsistent. Objective: To examine the relationships between intraoperative facial nerve branch transection and both postoperative outcome and functional deficits. Methods: SN cases, with minimal follow-up of 4 months, were retrospectively identified between 2019 and 2021; outcome was assessed using FaCE instrument, eFACE and Emotrics. Correlations between intraoperative facial nerve branch preservation or transection, and functional outcome and new functional deficits were examined. Results: Fifty-six cases were performed: 88% were females, and median age was 53 years (range 11-81). Mean follow-up was 19.5 months (range 4-42). Oral commissure excursion improved in patients where all smile branches were preserved, no vertical vector smile branches were transected, and more than three smile antagonist branches were transected. A linear trend between smile antagonist branch sacrifice and favorable smile outcome was found. Lower lip movement was improved in patients in whom more than half of the identified lower lip branches were transected. Thirty percent of patients experienced untoward postoperative functional deficits, from which 47% recovered with interventions. Conclusions: Several correlations between SN intra-operative decisions and outcome were identified; new or worsening functional deficit rate can be high. However, chemodenervation or fillers can help diminish these deficits.

Introduction: End-stage kidney disease (ESKD) is an established risk factor for chronic limb-threatening ischemia (CLTI). Procedural location for ESKD patients has not been well described. This study aims to examine variation in index procedural location in ESKD versus non-ESKD patients undergoing peripheral vascular intervention for CLTI and identify preoperative risk factors for tibial interventions., Methods: Chronic limb-threatening ischemia (CLTI) patients were identified in the Vascular Quality Initiative (VQI) peripheral vascular intervention dataset. Patient demographics and comorbidities were compared between patients with and without ESKD and those undergoing index tibial versus nontibial interventions. A multivariable logistic regression evaluating risk factors for tibial intervention was conducted., Results: A total of 23,480 procedures were performed on CLTI patients with 13.6% (n = 3154) with ESKD. End-stage kidney disease (ESKD) patients were younger (66.56 ± 11.68 versus 71.66 ± 12.09 y old, P = 0.019), more often Black (40.6 versus 18.6%, P < 0.001), male (61.2 versus 56.5%, P < 0.001), and diabetic (81.8 versus 60.0%, P < 0.001) than non-ESKD patients. Patients undergoing index tibial interventions had higher rates of ESKD (19.4 versus 10.6%, P < 0.001) and diabetes (73.4 versus 57.5%, P < 0.001) and lower rates of smoking (49.9 versus 73.0%, P < 0.001) than patients with nontibial interventions. ESKD (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.52-1.86, P < 0.001), Black race (OR 1.19, 95% CI 1.09-1.30, P < 0.001), and diabetes (OR 1.82, 95% CI 1.71-2.00, P < 0.001) were risk factors for tibial intervention., Conclusions: Patients with ESKD and CLTI have higher rates of diabetes and tibial disease and lower rates of smoking than non-ESKD patients. Tibial disease was associated with ESKD, diabetes, and Black race., (Published by Elsevier Inc.)

Objective: In head and neck ablative surgery, traditional teaching is that the key facial nerve branch to preserve along the plane of the lower border of the mandible is the marginal mandibular branch (MMb), which is considered to control all lower lip musculature. The depressor labii inferioris (DLI) is the muscle responsible for pleasing lower lip displacement and lower dental display during natural emotive smiling., Study Design: To understand the structure/function relationships of the distal lower facial nerve branches and lower lip musculature., Setting: In vivo extensive facial nerve dissections under general anesthesia., Methods: Intraoperative mapping was performed in 60 cases, using branch stimulation and simultaneous movement videography., Results: In nearly all cases, the MMb innervated the depressor anguli oris, lower orbicularis oris, and mentalis muscles. The nerve branches controlling DLI function were identified 2 ± 0.5 cm below the angle of the mandible, originating from a cervical branch, separately and inferior to MMb. In half of the cases, we identified at least 2 independent branches activating the DLI, both within the cervical region., Conclusion: An appreciation of this anatomical finding may help prevent lower lip weakness following neck surgery. Avoiding the functional and cosmetic consequences that accompany loss of DLI function would have a significant impact on the burden of potentially preventable sequelae that the head and neck surgical patient frequently carries., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: End-stage kidney disease (ESKD) is a risk factor for peripheral arterial disease and major adverse limb events following infra-inguinal bypass. Despite comprising an important patient population, ESKD patients are rarely analyzed as a subgroup and are underrepresented in vascular surgery guidelines. This study aims to compare the long-term outcomes of patients with and without ESKD undergoing endovascular peripheral vascular intervention (PVI) for chronic limb-threatening ischemia (CLTI)., Methods: CLTI patients with and without ESKD from 2007-2020 were identified in the Vascular Quality Initiative PVI dataset. Patients with prior bilateral interventions were excluded. Patients undergoing femoral-popliteal and tibial interventions were included. Mortality, reintervention, amputation, and occlusion rates at 21 months following intervention were examined. Statistical analyses were completed with the t-test, chi-square, and Kaplan-Meier curves., Results: The ESKD cohort was younger (66.4 ± 11.8 vs. 71.6 ± 12.1 years, P < 0.001) with higher rates of diabetes (82.2 vs. 60.9%, P < 0.001) the non-ESKD cohort. Long-term follow-up was available for 58.4% (N = 2,128 procedures) of ESKD patients and 60.8% (N = 13,075 procedures) of non-ESKD patients. At 21 months, ESKD patients had a higher mortality (41.7 vs. 17.4%, P < 0.001) and a higher amputation rate (22.3 vs. 7.1%, P < 0.001); however, they had a lower reintervention rate (13.2 vs. 24.6%, P < 0.001)., Conclusions: CLTI patients with ESKD have worse long-term outcomes at 2 years following PVI than non-ESKD patients. Mortality and amputation are higher with ESKD, while the reintervention rate is lower. Development of guidelines within the ESKD population has the potential to improve limb salvage., (Published by Elsevier Inc.)

Background: Enhanced recovery pathways (ERPs) aim to lower perioperative stress to facilitate recovery. Limited fasting combined with carbohydrate loading is a common ERP element. The effect of limited fasting has not been elucidated in patients with diabetes. Given the known deleterious effects of poor glycemic control in the perioperative period, such as increased rates of surgical site infection, the associations of preoperative limited fasting with perioperative glycemic control and early outcomes after lower extremity bypass (LEB) were investigated., Methods: A single institutional retrospective review of patients who underwent infrainguinal LEB from 2016 to 2022 was performed. The ERP was initiated in May 2018. Patients were stratified by diabetes diagnosis and preoperative hemoglobin A1C (HbA1C) levels. Perioperative glycemic control was compared between the limited fasting and traditional fasting patients (nil per os at midnight). Limited fasting was defined as a clear liquid diet until 2 hours before surgery with recommended carbohydrate loading consisting of 400 cc of a clear sports drink (approximately 30 g of carbohydrates). All limited fasting patients were within the ERP. Early perioperative hyperglycemia (EPH) was defined as blood glucose of >180 mg/dL within the first 24 hours of surgery. Perioperative outcomes such as surgical site infection, readmission, reinterventions, and complications were also compared., Results: A total of 393 patients were included (limited fasting patients N = 135; traditional fasting patients N = 258). A trend toward EPH was seen in all limited fasting groups. Evaluating limited fasting within diabetic patients revealed that 74.5% of limited fasting-diabetic patients had EPH compared with 49.6% of traditional fasting-diabetic patients (P = .001). When stratified by the HbA1C level, a significantly higher rate of EPH was seen in the HbA1c >8.0% groups, with 90.5% in the limited fasting patients compared with 67.9% in traditional fasting patients (P = .05). Limited fasting-diabetic patients experience a longer postoperative length of stay at 5.0 days (interquartile range: 3, 9) vs 4.0 days (2, 6) in nondiabetic patients (P = .016)., Conclusions: ERP limited fasting was associated with early perioperative hyperglycemia after LEB, particularly in patients with HbA1C >8.0%. Due to the high prevalence of diabetic patients undergoing LEB under ERP, the role of limited fasting and common glycemic elements of ERP may need to be re-evaluated in this subpopulation., (Published by Elsevier Inc.)

Atherosclerotic carotid artery disease has been well studied over the last half-century by multiple randomized controlled trials attempting to elucidate the appropriate modality of therapy for this disease process. Surgical techniques have evolved from carotid artery endarterectomy and transfemoral carotid artery stenting to the development of hybrid techniques in transcarotid artery revascularization. In this article, the authors provide a review of the available literature regarding operative and medical management of carotid artery disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Anatomic remodeling within the thoracic aorta following thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) has been well documented. However, less is known about the response of the untreated visceral aorta. In the present study, we investigated the visceral aortic behavior after TEVAR for acute or subacute TBAD to identify any associations with the clinical outcomes., Methods: A multicenter retrospective review was performed of all imaging studies for all patients who had undergone TEVAR for acute (0-14 days) and subacute (14-90 days) nontraumatic TBAD from 2006 to 2020. The cohort was inclusive of those with uncomplicated, high-risk, and complicated (defined in accordance with the Society for Vascular Surgery reporting guidelines) dissections. Centerline aortic measurements of the true and false lumen and total aortic diameter (TAD) were taken at standardized locations relative to the aortic anatomy within each aortic zone (the zones were defined by the Society for Vascular Surgery reporting guidelines). Diameter changes over time were evaluated using repeated measures mixed effects linear growth modeling. Visceral segment instability (VSI) was defined as any growth in the TAD of ≥5 mm within aortic zones 5 through 9., Results: A total of 82 patients were identified. The median length of imaging follow-up was 2.1 years (interquartile range, 0.75-4.5 years), with 15% of the cohort having follow-up >5 years. VSI was present in 55% of the cohort, with an average maximal increase in the TAD of 10.4 ± 6.3 mm during a median follow-up of 2.1 years (interquartile range, 0.75-4.5 years). Approximately one third of the cohort had experienced rapid VSI (growth ≥5 mm in the first year), and 4.8% of the cohort had developed a large paravisceral aortic aneurysm (TAD ≥5 cm) secondary to VSI. Linear growth modeling identified significant predictable growth in the TAD across all visceral zones. Zone 7 had the highest rate of TAD dilation, with a fixed effect estimated rate of 1.3 mm/y (95% confidence interval [CI], 0.23-2.1; P = .022). The preoperative factor most strongly associated with VSI was a cumulative number of zones dissected of six or more (odds ratio, 6.4; 95% CI, 1.07-8.6; P = .041). The odds for aortic reintervention were significantly increased for cases in which VSI led to the development of a paravisceral aortic aneurysm of ≥5 cm (odds ratio, 3.7; 95% CI, 1.1-13; P = .038)., Conclusions: VSI was identified in most patients who had undergone TEVAR for management of acute and subacute TBAD. The preoperative anatomic features such as the dissection extent, rather than the procedural details of graft coverage, might play a more significant role in VSI occurrence. Significant TAD growth had occurred in all visceral segments. These results highlight the importance of lifelong surveillance following TEVAR and identified a subset of patients who might have an increased risk of reintervention., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose of the Program: This article provides guidance on optimizing the management of pediatric patients with end-stage kidney disease (ESKD) who will be or are being treated with any form of home or in-center dialysis during the COVID-19 pandemic. The goals are to provide the best possible care for pediatric patients with ESKD during the pandemic and ensure the health care team's safety., Sources of Information: The core of these rapid guidelines is derived from the Canadian Society of Nephrology (CSN) consensus recommendations for adult patients recently published in the Canadian Journal of Kidney Health and Disease ( CJKHD ). We also consulted specific documents from other national and international agencies focused on pediatric kidney health. Additional information was obtained by formal review of the published academic literature relevant to pediatric home or in-center hemodialysis., Methods: The Leadership of the Canadian Association of Paediatric Nephrologists (CAPN), which is affiliated with the CSN, solicited a team of clinicians and researchers with expertise in pediatric home and in-center dialysis. The goal was to adapt the guidelines recently adopted for Canadian adult dialysis patients for pediatric-specific settings. These included specific COVID-19-related themes that apply to dialysis in a Canadian environment, as determined by a group of senior renal leaders. Expert clinicians and nurses with deep expertise in pediatric home and in-center dialysis reviewed the revised pediatric guidelines., Key Findings: We identified 7 broad areas of home dialysis practice management that may be affected by the COVID-19 pandemic: (1) peritoneal dialysis catheter placement, (2) home dialysis training, (3) home dialysis management, (4) personal protective equipment, (5) product delivery, (6) minimizing direct health care providers and patient contact, and (7) caregivers support in the community. In addition, we identified 8 broad areas of in-center dialysis practice management that may be affected by the COVID-19 pandemic: (1) identification of patients with COVID-19, (2) hemodialysis of patients with confirmed COVID-19, (3) hemodialysis of patients not yet known to have COVID-19, (4) management of visitors to the dialysis unit, (5) handling COVID-19 testing of patients and staff, (6) safe practices during resuscitation procedures in a pandemic, (7) routine hemodialysis care, and (8) hemodialysis care under fixed dialysis resources. We make specific suggestions and recommendations for each of these areas., Limitations: At the time when we started this work, we knew that evidence on the topic of pediatric dialysis and COVID-19 would be severely limited, and our resources were also limited. We did not, therefore, do formal systematic review or meta-analysis. We did not evaluate our specific suggestions in the clinical environment. Thus, this article's advice and recommendations are primarily expert opinions and subject to the biases associated with this level of evidence. To expedite the publication of this work, we created a parallel review process that may not be as robust as standard arms' length peer-review processes., Implications: We intend these recommendations to help provide the best care possible for pediatric patients prescribed in-center or home dialysis during the COVID-19 pandemic, a time of altered priorities and reduced resources., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Purpose: To collate best practice recommendations on the management of patients receiving in-center hemodialysis during the COVID-19 pandemic, based on published reports and current public health advice, while considering ethical principles and the unique circumstances of Canadian hemodialysis units across the country., Sources of Information: The workgroup members used Internet search engines to retrieve documents from provincial and local hemodialysis programs; provincial public health agencies; the Centers for Disease Control and Prevention; webinars and slides from other kidney agencies; and nonreviewed preprints. PubMed was used to search for peer-reviewed published articles. Informal input was sought from knowledge users during a webinar., Methods: Challenges in the care of hemodialysis patients during the COVID-19 pandemic were highlighted within the Canadian Senior Renal Leaders Forum discussion group. The Canadian Society of Nephrology (CSN) developed the COVID-19 rapid response team (RRT) to address these challenges. They identified a pan-Canadian team of clinicians and administrators with expertise in hemodialysis to form the workgroup. One lead was chosen who drafted the initial document. Members of the workgroup reviewed and discussed all recommendations in detail during 2 virtual meetings on April 7 and April 9. Disagreements were resolved by consensus. The document was reviewed by the CSN COVID-19 RRT, an ethicist, an infection control expert, a community nephrologist, and a patient partner. Content was presented during an interactive webinar on April 11, 2020 attended by 269 kidney health professionals, and the webinar and first draft of the document were posted online. Final revisions were made based on feedback received until April 13, 2020. CJKHD editors reviewed the parallel process peer review and edited the manuscript for clarity., Key Findings: Recommendations were made under the following themes: (1) Identification of patients with COVID-19 in the dialysis unit, (2) hemodialysis of patients with confirmed COVID-19, (3) hemodialysis of patients not yet known to have COVID-19, (4) visitors; (5) testing for COVID-19 in the dialysis unit; (6) resuscitation, (6) routine hemodialysis care, (7) hemodialysis care under fixed dialysis resources., Limitations: Because of limitations of time and resources, and the large number of questions, formal systematic review was not undertaken. The recommendations are based on expert opinion and subject to bias. The parallel review process that was created may not be as robust as the standard peer review process., Implications: We hope that these recommendations provide guidance for dialysis unit directors, clinicians, and administrators on how to limit risk from infection and adverse outcomes, while providing necessary dialysis care in a setting of finite resources. We also identify a number of resource allocation priorities, which we hope will inform decisions at provincial funding agencies., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Patients with congenital heart disease have high heart transplant waitlist mortality, and mechanical support is suboptimal. To evaluate feasibility of cardiac grafts from a genetically engineered triple-knockout pig as a bridge to allotransplantation, preformed anti-pig antibodies were measured in pediatric and adult patients., Methods: Flow cytometry measured serum immunoglobulin M (IgM) or IgG binding to wild-type and triple-knockout red blood cells (RBCs), with binding to human O-negative RBCs as a negative control. Group 1 comprise 84 pediatric patients and 64 healthy adults' sera with no previous cardiac surgery. Group 2 comprised 25 infant's sera postcardiac surgery, including 10 after palliation for hypoplastic left heart syndrome., Results: In group 1, IgM binding to wild-type RBCs occurred in 80% of sera and IgG binding occurred in in 91% of sera. Only 3% of sera showed IgM binding to triple-knockout RBCs, and 1 (<1%) was weakly positive for IgG binding. In group 2, all 25 infants demonstrated increased IgM and IgG binding to wild-type RBCs. One patient showed minimal IgM and another showed low IgG binding to triple-knockout RBCs. No infant after stage 1 Norwood demonstrated any IgG or IgM binding., Conclusions: Preformed anti-pig antibodies may not be a barrier to heart xenotransplantation in infants, even after cardiac surgery. With adequate immunosuppressive therapy, a triple-knockout pig heart transplant might function successfully as a bridge to allotransplantation., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Masseteric- or deep temporal-to-facial nerve transfer (five-to-seven nerve transfer) is increasingly used in facial reanimation; however, the indications and clinical variables affecting outcomes for five-to-seven nerve transfer have not been defined. The authors describe their early experience with five-to-seven nerve transfer, reporting function and patient-reported outcomes, to identify potential parameters that are predictive of outcome., Methods: The authors conducted a retrospective chart review of all patients who underwent five-to-seven nerve transfer for smile reanimation from 2012 to 2017. Age, sex, cause of facial paralysis, onset and duration of paralysis, history of adjuvant chemotherapy and/or radiation therapy, donor nerve used, adjunctive procedures, and final excursion were recorded. Standard photographs and videos, and data regarding clinical facial nerve function and patient-reported quality of life, were obtained preoperatively and postoperatively., Results: Sixty patients were identified. Forty-seven had flaccid facial paralysis and 13 had postparalysis facial palsy. Among flaccid facial paralysis patients, masseteric nerve transfer was successful in 30 patients (88 percent) and deep temporal nerve transfer was successful in three cases (60 percent). Among postparalysis facial palsy patients, five-to-seven nerve transfer was successful in two patients (20 percent). Average quality-of-life scores improved significantly from preoperatively (46) to postoperatively (59) among flaccid facial paralysis patients with successful five-to-seven nerve transfer., Conclusions: Five-to-seven nerve transfer is a viable option in facial reanimation. Shorter denervation times and preoperative flaccidity are favorable predictors of outcome. Five-to-seven nerve transfer as an adjunct to primary repair appears highly effective for enhancing smile function. Five-to-seven nerve transfer results are not reliable in patients with postparalysis facial palsy., Clinical Question/level of Evidence: Therapeutic, IV.

ELL family transcription factors activate the overall rate of RNA polymerase II (Pol II) transcription elongation by binding directly to Pol II and suppressing its tendency to pause. In metazoa, ELL regulates Pol II transcription elongation as part of a large multisubunit complex referred to as the Super Elongation Complex (SEC), which includes P-TEFb and EAF, AF9 or ENL, and an AFF family protein. Although orthologs of ELL and EAF have been identified in lower eukaryotes including Schizosaccharomyces pombe, it has been unclear whether SEC-like complexes function in lower eukaryotes. In this report, we describe isolation from S. pombe of an ELL-containing complex with features of a rudimentary SEC. This complex includes S. pombe Ell1, Eaf1, and a previously uncharacterized protein we designate Ell1 binding protein 1 (Ebp1), which is distantly related to metazoan AFF family members. Like the metazoan SEC, this S. pombe ELL complex appears to function broadly in Pol II transcription. Interestingly, it appears to have a particularly important role in regulating genes involved in cell separation.

There is a continuing need for donor hearts for infants with complex congenital heart defects. The transplantation of hearts from neonatal pigs would be an alternative to human organs, particularly if donor-specific immunological tolerance could be achieved. The great majority of infant humans do not make natural (preformed) antibodies against triple-knockout (TKO) pigs (that do not express any of the three known pig antigens against which humans have natural anti-pig antibodies). The transplantation of a heart from a TKO pig into an infant would therefore minimize any risk of early antibody-mediated rejection, and, with adequate immunosuppressive therapy, prolonged graft survival may well be achieved. Total host thymectomy (commonly carried out at the time of orthotopic heart transplantation in this age group) ± residual T-cell depletion and donor-specific pig thymus tissue transplantation might induce T-cell tolerance and allow immunosuppressive therapy to be discontinued (if there is in vitro evidence of T-cell and B-cell nonresponsiveness to donor-specific pig cells). Even if tolerance were not achieved, with continuing immunosuppressive therapy, the graft would likely "bridge" the patient until a suitable allograft became available or be associated with prolonged xenograft function., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The purpose of this study was to determine whether differences in long-term facial function outcomes following acute Lyme disease-associated facial palsy (LDFP) exist between patients who received antibiotic monotherapy (MT); dual therapy (DT) with antibiotics and corticosteroids; and triple therapy (TT) with antibiotics, corticosteroids, and antivirals., Study Design: Retrospective cohort., Methods: All patients with a prior diagnosis of unilateral LDFP who presented to our center between 2002 and 2015 were retrospectively assessed for inclusion. Two blinded experts graded static, dynamic, and synkinesis parameters of facial functions using standardized video documentation of facial function., Results: Fifty-one patients were included. The mean time of assessment following LDFP onset was 15.1 months (range 0.3-84 months). Significantly worse facial outcomes were seen among those who received DT and TT as compared to those who received MT, most pronounced among those assessed 12 months or later following onset of LDFP (Dynamic-P = 0.031, post hoc MT vs. TT: mean difference [MD], 15.83; 95% confidence interval [CI], 1.54-30.13; P = 0.030. Synkinesis-P = 0.026, post hoc MT vs. DT: MD, 21.50; 95% CI, 0.68-42.32; P = 0.043, post hoc MT vs. TT: MD, 19.22; 95% CI, 2.23-36.22; P = 0.027)., Conclusion: An association between corticosteroid use in acute LDFP and worse long-term facial function outcomes has been demonstrated. Care should be taken in differentiating viral or idiopathic facial palsy (e.g., Bell palsy) from LDFP., Level of Evidence: 4. Laryngoscope, 127:1451-1458, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Use of a robust high-resolution instrument for grading of facial symmetry would enhance reporting the outcomes of facial reanimation interventions. The eFACE is one such tool., Objective: To determine test-retest reliability of the eFACE tool over time and agreement between eFACE assessments made in person vs those made using video of facial mimetic function., Design, Setting, and Participants: A prospective observational study was conducted among 75 consecutive patients with varying degrees of facial palsy who presented between July 1 and December 31, 2014, to an academic tertiary referral hospital. Facial symmetry of all patients was graded in person and via standardized photographic and video documentation of facial mimetic function at the initial visit. Three months after initial presentation, eFACE scores were reassessed by the same raters using the videos of facial mimetic function documented at the initial visit., Main Outcomes and Measures: Individual and subset eFACE scores assessed by 2 facial reanimation surgeons., Results: Among the 75 patients in the study (mean [SD] age, 48.18 [16.60] years; 30 men and 45 women), agreement between in-person and video assessments of facial function using the eFACE scale was excellent (static subset score: mean difference, 0.19; 95% CI, -1.51 to 1.88; P = .83; intraclass correlation coefficient [ICC], 0.85; 95% CI, 0.80 to 0.89; dynamic subset score: mean difference, -0.51; 95% CI, -1.72 to 0.71; P = .41; ICC, 0.96; 95% CI, 0.94 to 0.97; synkinesis subset score: mean difference, -1.14; 95% CI, -2.87 to 0.59; P = .20; ICC, 0.90; 95% CI, 0.86 to 0.93; and composite score: mean difference, -0.41; 95% CI, -1.30 to 0.47; P = .36; ICC, 0.94; 95% CI, 0.92 to 0.96). Agreement between repeated eFACE assessments of video of facial function was excellent (static subset score: ICC, 0.93; 95% CI, 0.87 to 0.96; dynamic subset score: ICC, 0.88; 95% CI, 0.80 to 0.94; synkinesis subset score: ICC, 0.92; 95% CI, 0.86 to 0.96; and composite score: ICC, 0.96; 95% CI, 0.93 to 0.98)., Conclusions and Relevance: Strong agreement exists between eFACE scores of facial function assessed in person and from video recordings. Test-retest reliability of eFACE scores is high. The eFACE is a reliable instrument for high-resolution assessment of facial mimetic function., Level of Evidence: NA.

Background: The electronic, clinician-graded facial function scale (eFACE) is a potentially useful tool for assessing facial function. Beneficial features include its digital nature, use of visual analogue scales, and provision of graphic outputs and scores. The authors introduced the instrument to experienced facial nerve clinicians for feedback, and examined the effect of viewing a video tutorial on score agreement., Methods: Videos of 30 patients with facial palsy were embedded in an Apple eFACE application. Facial nerve clinicians were invited to perform eFACE video rating and tutorial observation. Participants downloaded the application, viewed the clips, and applied the scoring. They then viewed the tutorial and rescored the clips. Analysis of mean, standard deviation, and confidence interval were performed. Values were compared before and after tutorial viewing, and against scores obtained by an experienced eFACE user., Results: eFACE feedback was positive; participants reported eagerness to apply the instrument in clinical practice. Standard deviation decreased significantly in only two of the 16 categories after tutorial viewing. Subscores for static, dynamic, and synkinesis all demonstrated stable standard deviations, suggesting that the instrument is intuitive. Participants achieved posttutorial scores closer to the experienced eFACE user in 14 of 16 scores, although only a single score, nasolabial fold orientation with smiling, achieved statistically significant improvement., Conclusions: The eFACE may be a suitable, cross-platform, digital instrument for facial function assessment, and was well received by facial nerve experts. Tutorial viewing does not appear to be necessary to achieve agreement, although it does mildly improve agreement between occasional and frequent eFACE users.

Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based proteomics has been used in breast cancer research for over two decades to elucidate protein function. Breast cancer is a heterogeneous group of diseases with distinct molecular features that are reflected in tumour characteristics and clinical outcomes. Compared with all other subtypes of breast cancer, triple-negative breast cancer is perhaps the most distinct in nature and heterogeneity. In this review, we provide an introductory overview of the application of advanced proteomic technologies to triple-negative breast cancer research., Competing Interests: CONFLICT OF INTREST The authors declare that they have no conflict of interest.

The NF-κB family of transcription factors is pivotal in controlling cellular responses to environmental stresses; abnormal nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling features in many autoimmune diseases and cancers. Several components of the NF-κB signaling pathway have been reported to interact with the protein TNIP2 (also known as ABIN2), and TNIP2 can both positively and negatively regulate NF-κB- dependent transcription of target genes. However, the function of TNIP2 remains elusive and the cellular machinery associating with TNIP2 has not been systematically defined. Here we first used a broad MudPIT/Halo Affinity Purification Mass Spectrometry (AP-MS) approach to map the network of proteins associated with the NF-κB transcription factors, and establish TNIP2 as an NF-κB network hub protein. We then combined AP-MS with biochemical approaches in a more focused study of truncated and mutated forms of TNIP2 to map protein associations with distinct regions of TNIP2. NF-κB interacted with the N-terminal region of TNIP2. A central region of TNIP2 interacted with the endosomal sorting complex ESCRT-I via its TSG101 subunit, a protein essential for HIV-1 budding, and a single point mutant in TNIP2 disrupted this interaction. The major gene ontology category for TNIP2 associated proteins was mRNA metabolism, and several of these associations, like KHDRBS1, were lost upon depletion of RNA. Given the major association of TNIP2 with mRNA metabolism proteins, we analyzed the RNA content of affinity purified TNIP2 using RNA-Seq. Surprisingly, a specific limited number of mRNAs was associated with TNIP2. These RNAs were enriched for transcription factor binding, transcription factor cofactor activity, and transcription regulator activity. They included mRNAs of genes in the Sin3A complex, the Mediator complex, JUN, HOXC6, and GATA2. Taken together, our findings suggest an expanded role for TNIP2, establishing a link between TNIP2, cellular transport machinery, and RNA transcript processing., Competing Interests: The authors declare that they have no conflict of interest., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes. Without relying on sequence or structure information, SONAR identifies 1,923 human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs, revealing unexpected RNA binding activity for disease-relevant proteins and DNA binding proteins., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Bilateral facial palsy is a rare clinical entity caused by myriad disparate conditions requiring different treatment paradigms. Lyme disease, Guillain-Barré syndrome, and leukemia are several examples. In this article, the authors describe the cause, the initial diagnostic approach, and the management of long-term sequelae of bilateral paralysis that has evolved in the authors' center over the past 13 years., Methods: A chart review was performed to identify all patients diagnosed with bilateral paralysis at the authors' center between January of 2002 and January of 2015. Demographics, signs and symptoms, diagnosis, initial medical treatment, interventions for facial reanimation, and outcomes were reviewed., Results: Of the 2471 patients seen at the authors' center, 68 patients (3 percent) with bilateral facial paralysis were identified. Ten patients (15 percent) presented with bilateral facial paralysis caused by Lyme disease, nine (13 percent) with Möbius syndrome, nine (13 percent) with neurofibromatosis type 2, five (7 percent) with bilateral facial palsy caused by brain tumor, four (6 percent) with Melkersson-Rosenthal syndrome, three (4 percent) with bilateral temporal bone fractures, two (3 percent) with Guillain-Barré syndrome, one (2 percent) with central nervous system lymphoma, one (2 percent) with human immunodeficiency virus infection, and 24 (35 percent) with presumed Bell palsy. Treatment included pharmacologic therapy, physical therapy, chemodenervation, and surgical interventions., Conclusions: Bilateral facial palsy is a rare medical condition, and treatment often requires a multidisciplinary approach. The authors outline diagnostic and therapeutic algorithms of a tertiary care center to provide clinicians with a systematic approach to managing these complicated patients.

Importance: A universal, health care professional-graded scale for facial assessment would be a useful tool for reporting, comparing, and assessing facial function among patients with facial paralysis., Objectives: To correlate scores of an assessment tool, the eFACE scale, with expert-rated facial disfigurement and to determine the relative contributions of facial features to facial palsy-related disfigurement., Design, Setting, and Participants: The eFACE scale yields 15 individual variable scores, in addition to subscores for static, dynamic, and synkinesis elements, and a total score that is based on 100-point scales. Two hundred patients with varying degrees of unilateral facial palsy underwent independent eFACE assessment and assignment of a disfigurement score by 2 facial nerve surgeons. The mean scores were determined, and multivariate regression analysis was performed to fit eFACE subset scores (static, dynamic, and synkinesis) to disfigurement ratings. A hybrid regression model was then used to weight each of the 15 eFACE variables, using stepwise regression to control for the effect of the other variables. Scoring was performed during an 8-week period from March 16 to May 8, 2015., Main Outcome and Measure: Use of the 100-point eFACE variables, together with a 100-point visual analog scale of disfigurement, with 0 representing the most extreme disfigurement possible from a facial nerve disorder and 100 representing no discernible facial disfigurement., Results: In the 200 patients included in analysis (126 [63.0% female]; mean [SD] age, 46.5 [16.4] years]), predicted disfigurement scores based on eFACE subset scores demonstrated excellent agreement with surgeon-graded disfigurement severity (r2 = 0.79). Variable weighting demonstrated that the 6 key contributors to overall disfigurement were (in order of importance) nasolabial fold depth at rest (normalized coefficient [NC], 0.18; P < .001), oral commissure position at rest (NC, 0.15; P < .001), lower lip asymmetry while pronouncing the long /ē/ (NC, 0.09; P < .001), palpebral fissure width at rest (NC, 0.09; P < .001), nasolabial fold orientation with smiling (NC, 0.08; P = .001), and palpebral fissure width during attempts at full eye closure (NC, 0.06; P = .03)., Conclusions and Relevance: A mathematical association between eFACE-measured facial features and overall expert-graded disfigurement in facial paralysis has been established. For those using the eFACE grading scale, predictions of the specific effects of various interventions on expert-rated disfigurement are now possible and may guide therapy., Level of Evidence: NA.

Importance: Most rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System (FGS) to measure and detect changes in facial function. The eFACE, an electronic and digitally graded facial measurement scale, was recently created to provide similar information to the Sunnybrook FGS, but with scaling uniformity across all categories of facial function, graphical outputs, and easy-to-use visual analog scales., Objectives: To establish the correlation between the scores on the eFACE and the Sunnybrook FGS among patients with facial paralysis and to compare the reliability of the 2 scales., Design, Setting, and Participants: A retrospective review of medical records identified 109 patients who were evaluated at a facial nerve center by physical therapists using the eFACE and the Sunnybrook FGS on the same day, between November 1, 2014, and May 31, 2015. The level of facial function predicted using the 2 scales was compared to study correlation between the scales. Data analysis was conducted from June 1 to September 1, 2015., Main Outcomes and Measures: Correlation between the Sunnybrook FGS and the eFACE grading scale., Methods: Two independent physical therapists evaluated patients using both the eFACE and the Sunnybrook FGS. Scores were compared and the Spearman rank correlation coefficient was calculated between the total scores and each of the 3 subscores, including static, dynamic, and synkinesis scores. The total Sunnybrook FGS synkinesis score (worst score, 15; perfect score, 0) and static score (worst score, 20; perfect score, 0) were normalized to a 100-point scale with the eFACE (perfect score, 100; worst score, 1)., Results: eFACE scores ranged from 48 to 100, and Sunnybrook FGS scores ranged from 0 to 100. Among 109 patients, there was a moderately strong correlation between eFACE and Sunnybrook FGS scores in both total and subcategory scores. The Spearman rank correlation coefficient of the total eFACE and Sunnybrook FGS was 0.75 (r < 0.0001). For the static scores, the correlation coefficient was -0.71 (r < 0.0001). The correlation coefficients for the dynamic and synkinesis scores were 0.77 (r < 0.0001) and -0.78 (r < 0.0001), respectively., Conclusions and Relevance: There is moderately good agreement between the Sunnybrook FGS and the eFACE. Given the ease of using the eFACE on mobile devices, as well as its additional functionality, it may represent a reasonable facial grading option across disciplines in the future., Level of Evidence: NA.

Proteins that respond to DNA damage play critical roles in normal and diseased states in human biology. Studies have suggested that the S. cerevisiae protein CMR1/YDL156w is associated with histones and is possibly associated with DNA repair and replication processes. Through a quantitative proteomic analysis of affinity purifications here we show that the human homologue of this protein, WDR76, shares multiple protein associations with the histones H2A, H2B, and H4. Furthermore, our quantitative proteomic analysis of WDR76 associated proteins demonstrated links to proteins in the DNA damage response like PARP1 and XRCC5 and heterochromatin related proteins like CBX1, CBX3, and CBX5. Co-immunoprecipitation studies validated these interactions. Next, quantitative imaging studies demonstrated that WDR76 was recruited to laser induced DNA damage immediately after induction, and we compared the recruitment of WDR76 to laser induced DNA damage to known DNA damage proteins like PARP1, XRCC5, and RPA1. In addition, WDR76 co-localizes to puncta with the heterochromatin proteins CBX1 and CBX5, which are also recruited to DNA damage but much less intensely than WDR76. This work demonstrates the chromatin and DNA damage protein associations of WDR76 and demonstrates the rapid response of WDR76 to laser induced DNA damage.

Importance: The ability of patients with unilateral facial paralysis to recognize and appropriately judge facial expressions remains underexplored., Objective: To test the effects of unilateral facial paralysis on the recognition of and judgments about facial expressions of emotion and to evaluate the asymmetry of facial mimicry., Design, Setting, and Participants: Patients with left or right unilateral facial paralysis at a university facial plastic surgery unit completed 2 computer tasks involving video facial expression recognition. Side of facial paralysis was used as a between-participant factor. Facial function and symmetry were verified electronically with the eFACE facial function scale., Exposures: Across 2 tasks, short videos were shown on which facial expressions of happiness and anger unfolded earlier on one side of the face or morphed into each other. Patients indicated the moment or side of change between facial expressions and judged their authenticity., Main Outcomes and Measures: Type, time, and accuracy of responses on a keyboard were analyzed., Results: A total of 57 participants (36 women and 21 men) aged 20 to 76 years (mean age, 50.2 years) and with mild left or right unilateral facial paralysis were included in the study. Patients with right facial paralysis were faster (by about 150 milliseconds) and more accurate (mean number of errors, 1.9 vs 2.5) to detect expression onsets on the left side of the stimulus face, suggesting anatomical asymmetry of facial mimicry. Patients with left paralysis, however, showed more anomalous responses, which partly differed by emotion., Conclusions and Relevance: The findings favor the hypothesis of an anatomical asymmetry of facial mimicry and suggest that patients with a left hemiparalysis could be more at risk of developing a cluster of disabilities and psychological conditions including emotion-recognition impairments., Level of Evidence: 3.

The highly conserved yeast R2TP complex, consisting of Rvb1, Rvb2, Pih1, and Tah1, participates in diverse cellular processes ranging from assembly of protein complexes to apoptosis. Rvb1 and Rvb2 are closely related proteins belonging to the AAA+ superfamily and are essential for cell survival. Although Rvbs have been shown to be associated with various protein complexes including the Ino80 and Swr1chromatin remodeling complexes, we performed a systematic quantitative proteomic analysis of their associated proteins and identified two additional complexes that associate with Rvb1 and Rvb2: the chaperonin-containing T-complex and the 19S regulatory particle of the proteasome complex. We also analyzed Rvb1 and Rvb2 purified from yeast strains devoid of PIH1 and TAH1. These analyses revealed that both Rvb1 and Rvb2 still associated with Hsp90 and were highly enriched with RNA polymerase II complex components. Our analyses also revealed that both Rvb1 and Rvb2 were recruited to the Ino80 and Swr1 chromatin remodeling complexes even in the absence of Pih1 and Tah1 proteins. Using further biochemical analysis, we showed that Rvb1 and Rvb2 directly interacted with Hsp90 as well as with the RNA polymerase II complex. RNA-Seq analysis of the deletion strains compared with the wild-type strains revealed an up-regulation of ribosome biogenesis and ribonucleoprotein complex biogenesis genes, down-regulation of response to abiotic stimulus genes, and down-regulation of response to temperature stimulus genes. A Gene Ontology analysis of the 80 proteins whose protein associations were altered in the PIH1 or TAH1 deletion strains found ribonucleoprotein complex proteins to be the most enriched category. This suggests an important function of the R2TP complex in ribonucleoprotein complex biogenesis at both the proteomic and genomic levels. Finally, these results demonstrate that deletion network analyses can provide novel insights into cellular systems., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: The subjective nature of facial aesthetics and the difficulties associated with quantifying facial function have made outcomes analysis in facial paralysis challenging. Clinicians rely on photographs, subjective descriptions, and scales, limiting assessment, communication among providers, and communication between providers and patients. The authors describe the development and validation of a comprehensive, electronic, clinician-graded facial function scale (eFACE), which generates an overall disfigurement score and offers simple graphic output for clinician communication, assessment of various interventions, and patient understanding. The eFACE application may be used in a variety of electronic devices, including smartphones, tablets, and computers., Methods: An instrument consisting of 16 items in a visual analogue scale format was developed to assess facial function and symmetry (the eFACE). Video recordings of subjects performing facial expressions were viewed, and the eFACE instrument was applied, along with an overall facial disfigurement score. A multiple regression analysis was performed to determine the best linear relationship between overall expert-determined disfigurement and the eFACE items. The resulting equation was tested by three independent facial nerve clinicians, using an additional series of patients, to determine both interrater and intrarater reliability of the instrument., Results: Multiple regression analysis produced good fit of eFACE parameters to overall expert-rated global facial disfigurement when dynamic parameters were weighted twice as heavily as static and synkinesis parameters. eFACE scores demonstrated very high interrater and intrarater reliability., Conclusion: The eFACE is a reliable, reproducible, and straightforward digital clinical measure with which to assess facial function and disfigurement in patients with facial paralysis.

Background: The rodent model is commonly used to study facial nerve injury. Because of the exceptional regenerative capacity of the rodent facial nerve, it is essential to consider the timing when studying facial nerve regeneration and functional recovery. Short-term functional recovery data following transection and repair of the facial nerve has been documented by our laboratory. However, because of the limitations of the head fixation device, there is a lack of long-term data following facial nerve injury. The objective of this study was to elucidate the long-term time course and functional deficit following facial nerve transection and repair in a rodent model., Methods: Adult rats were divided into group 1 (controls) and group 2 (experimental). Group 1 animals underwent head fixation, followed by a facial nerve injury, and functional testing was performed from day 7 to day 70. Group 2 animals underwent facial nerve injury, followed by delayed head fixation, and then underwent functional testing from months 6 to 8., Results: There was no statistical difference between the average whisking amplitudes in group 1 and group 2 animals., Conclusion: Functional whisking recovery 6 months after facial nerve injury is comparable to recovery within 1 to 4 months of transection and repair, thus the ideal window for evaluating facial nerve recovery falls within the 4 months after injury., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

A common approach for exploring the interactome, the network of protein-protein interactions in cells, uses a commercially available ORF library to express affinity tagged bait proteins; these can be expressed in cells and endogenous cellular proteins that copurify with the bait can be identified as putative interacting proteins using mass spectrometry. Control experiments can be used to limit false-positive results, but in many cases, there are still a surprising number of prey proteins that appear to copurify specifically with the bait. Here, we have identified one source of false-positive interactions in such studies. We have found that a combination of: 1) the variable sequence of the C-terminus of the bait with 2) a C-terminal valine "cloning scar" present in a commercially available ORF library, can in some cases create a peptide motif that results in the aberrant co-purification of endogenous cellular proteins. Control experiments may not identify false positives resulting from such artificial motifs, as aberrant binding depends on sequences that vary from one bait to another. It is possible that such cryptic protein binding might occur in other systems using affinity tagged proteins; this study highlights the importance of conducting careful follow-up studies where novel protein-protein interactions are suspected.

Facial paralysis is a rare but severe condition in the pediatric population. Impaired facial movement has multiple causes and varied presentations, therefore individualized treatment plans are essential for optimal results. Advances in facial reanimation over the past 4 decades have given rise to new treatments designed to restore balance and function in pediatric patients with facial paralysis. This article provides a comprehensive review of pediatric facial rehabilitation and describes a zone-based approach to assessment and treatment of impaired facial movement., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Macrophages are major producers of inflammatory cytokines; however, their role in chronic rhinosinusitis (CRS) has not been clearly defined. The aim of this study was to quantify macrophages in sinus tissue of patients with various subtypes of CRS and determine the impact of atopic status on macrophage infiltrate., Study Design: Prospective immunohistochemical study of human sinonasal tissue., Setting: Academic medical center., Subjects and Methods: Human sinonasal tissue was taken from patients with CRS with nasal polyposis (CRSwNP, n = 8), CRS without nasal polyposis (CRSsNP, n = 8), and controls (n = 8) undergoing surgery for CSF leak repair or endoscopic excision of non-secreting pituitary tumor. Samples were immunohistochemically stained for macrophage/monocyte markers Mac387 and CD68., Results: CRSwNP patients had significantly increased numbers of Mac387 and CD68 cells compared to control patients (P < .05) or CRSsNP patients (P < .01). CRSsNP had significantly increased number of cells staining for CD68 compared to controls (P < .05). The increased presence of macrophages measured by either marker in CRSwNP was independent of atopic status., Conclusion: Macrophages are increased in CSRwNP patients regardless of atopic status and may contribute to the immunopathology of CRS., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

The development of affinity purification technologies combined with mass spectrometric analysis of purified protein mixtures has been used both to identify new protein-protein interactions and to define the subunit composition of protein complexes. Transcription factor protein interactions, however, have not been systematically analyzed using these approaches. Here, we investigated whether ectopic expression of an affinity tagged transcription factor as bait in affinity purification mass spectrometry experiments perturbs gene expression in cells, resulting in the false positive identification of bait-associated proteins when typical experimental controls are used. Using quantitative proteomics and RNA sequencing, we determined that the increase in the abundance of a set of proteins caused by overexpression of the transcription factor RelA is not sufficient for these proteins to then co-purify non-specifically and be misidentified as bait-associated proteins. Therefore, typical controls should be sufficient, and a number of different baits can be compared with a common set of controls. This is of practical interest when identifying bait interactors from a large number of different baits. As expected, we found several known RelA interactors enriched in our RelA purifications (NFκB1, NFκB2, Rel, RelB, IκBα, IκBβ, and IκBε). We also found several proteins not previously described in association with RelA, including the small mitochondrial chaperone Tim13. Using a variety of biochemical approaches, we further investigated the nature of the association between Tim13 and NFκB family transcription factors. This work therefore provides a conceptual and experimental framework for analyzing transcription factor protein interactions., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Saliva is known to play a crucial role in insect feeding behavior and virus transmission. Currently, little is known about the salivary glands and saliva of thrips, despite the fact that Frankliniella occidentalis (Pergande) (the western flower thrips) is a serious pest due to its destructive feeding, wide host range, and transmission of tospoviruses. As a first step towards characterizing thrips salivary gland functions, we sequenced the transcriptome of the primary salivary glands of F. occidentalis using short read sequencing (Illumina) technology. A de novo-assembled transcriptome revealed 31,392 high quality contigs with an average size of 605 bp. A total of 12,166 contigs had significant BLASTx or tBLASTx hits (E≤1.0E-6) to known proteins, whereas a high percentage (61.24%) of contigs had no apparent protein or nucleotide hits. Comparison of the F. occidentalis salivary gland transcriptome (sialotranscriptome) against a published F. occidentalis full body transcriptome assembled from Roche-454 reads revealed several contigs with putative annotations associated with salivary gland functions. KEGG pathway analysis of the sialotranscriptome revealed that the majority (18 out of the top 20 predicted KEGG pathways) of the salivary gland contig sequences match proteins involved in metabolism. We identified several genes likely to be involved in detoxification and inhibition of plant defense responses including aldehyde dehydrogenase, metalloprotease, glucose oxidase, glucose dehydrogenase, and regucalcin. We also identified several genes that may play a role in the extra-oral digestion of plant structural tissues including β-glucosidase and pectin lyase; and the extra-oral digestion of sugars, including α-amylase, maltase, sucrase, and α-glucosidase. This is the first analysis of a sialotranscriptome for any Thysanopteran species and it provides a foundational tool to further our understanding of how thrips interact with their plant hosts and the viruses they transmit.

Background: This study was designed to determine if differences in overall skull base thickness exist in patients with spontaneous cerebrospinal fluid (SCSF) leaks and to compare our institution's 10-year experience with the endoscopic repair of these leaks to the existing literature. A retrospective cohort study was performed in a tertiary rhinologic practice., Methods: A retrospective study by two blinded independent reviewers compared the skull base thickness on computerized tomography (CT) imaging in our SCSF leak patients to nonleaking controls and patients with traumatic CSF leaks. Surgical outcomes were compared with a pooled analysis of the published literature., Results: SCSF leaks were seen most commonly in obese, middle-aged women of African American descent. SCSF leak patients were shown to have thinner skull bases in the region of the ethmoid roof, lateral lamella, and anterior face of the sella (p < 0.05) compared with patients with traumatic leaks and nonleaking controls. No racial difference in skull base thickness was observed when patients were matched according to leak type. The success rate of primary endoscopic intervention in our patients was high at 94% and comparable with the published literature., Conclusion: Differences in skull base thickness exist in SCSF patients, but whether this predisposes to such leaks or is a consequence of the underlying pathophysiology remains unknown. The endoscopic endonasal approach provides a highly effective means of repairing such leaks with success rates comparable with the endoscopic repair of other leak types. Adjuvant measures including weight reduction, lumbar drain, and acetazolamide use may increase success rates and should be considered in their management.

Objective: To describe quadrivalent human papillomavirus (HPV) vaccination coverage achieved in the HPV vaccination catch-up program for girls aged 12-17 years., Design: Analysis of data from the Australian National HPV Vaccination Program Register., Participants: Girls aged 12-17 years as at 30 June 2007., Main Outcome Measures: HPV vaccine coverage by dose (1, 2 and 3), age and state of residence, using Australian Bureau of Statistics estimates of resident populations as the denominator., Results: Notified vaccination coverage for girls aged 12-17 years nationally was 83% for dose 1, 78% for dose 2 and 70% for dose 3. The Australian Capital Territory and Victoria recorded the highest three-dose coverage for the 12-17-year-old cohort overall at 75%. The highest national three-dose coverage rate by age was achieved in 12-year-olds (74%). In Queensland, coverage among Indigenous girls compared with non-Indigenous girls was lower with each dose (lower by 4% for dose 1, 10% for dose 2 and 15% for dose 3). This pattern was not seen in the NT, where initial coverage was 17% lower among Indigenous girls, but the course completion rate among those who started vaccination was identical (84%)., Conclusions: The catch-up HPV vaccination program delivered over 1.9 million doses of HPV vaccine to girls aged 12-17 years, resulting in 70% of girls in this age group being fully vaccinated. The range in coverage achieved and the lower uptake documented among Indigenous girls suggest that HPV vaccination programs can be further improved.

Objective: Report our experience with negative pressure wound therapy (NPWT) applied to massive scapular and latissimus free flap donor sites, in the setting of microvascular reconstruction for extensive head and neck defects., Study Design: Retrospective case series with chart review., Setting: Tertiary academic referral center., Subjects and Methods: Retrospective review was conducted of all patients who underwent scapular or latissimus free tissue transfer by the senior author for head and neck reconstruction, over a 5-year period (2006-2011). In addition to NPWT details, comprehensive patient data were abstracted and compiled, including demographics, operative details, hospital stay, postoperative follow-up, and donor site complications., Results: Ninety-four patients underwent reconstruction of extensive postablative head and neck defects using either a scapular or latissimus free flap. Mean harvested flap skin paddle size was 140 cm(2). All donor sites were closed primarily. Fifty-two patients (55%) had NPWT applied over closed donor site incisions postoperatively. The other 42 patients (45%) received only conventional incision care. Major donor site complications occurred in 12% (n = 5) of the patients who did not undergo NPWT, as compared with a 6% (n = 3) complication rate among patients in the NPWT-treated group., Conclusion: This is the first study to examine NPWT in the postoperative treatment of closed high-tension wounds following scapular or latissimus dorsi harvest for reconstruction of extensive head and neck defects. Our results suggest that NPWT is a safe technique in the management of massive scapular and latissimus free flap harvest sites that may decrease associated major donor wound complications.

Characterizing protein complexes and identifying their subunits promote our understanding of the machinery involved in many in vivo processes. Proteomic studies can identify a protein's binding partners, and this can provide insight into how protein complexes function and how they are regulated. In addition, the composition of a protein complex within an organism can be investigated as a function of time, as a function of location, or during the response of an organism to a change in environment. There are many ways to isolate a complex and identify its constituents. This review will focus on complex isolation using affinity purification and will address issues that biochemists should bear in mind as they isolate protein complexes for mass spectrometric analysis by multidimensional protein identification technology (MudPIT)(1). Protein complex analysis by mass spectrometry frequently involves the collaborative efforts of biochemists or biologists who purify protein complexes and proteomic specialists who analyze the samples - for fruitful collaborations it can be helpful for these specialized groups to be acquainted with basic principles of their collaborator's discipline. With this in mind, we first review the variety of affinity purification methods which might be considered for preparing complexes for analysis, and then provide brief primers on the principles of MudPIT mass spectrometry and data analysis. From this foundation, we then discuss how these techniques are integrated and optimized and suggest salient points to consider when preparing purified samples for protein identification, performing mass spectrometry runs, and analyzing the resulting data., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To provide an up-to-date review of the literature on the safety and efficacy of the endoscopic technique for cerebrospinal (CSF) leak repairs., Data Sources: PubMed, Medline/Old Medline, and Cochrane Central databases., Review Methods: Using the above outlined data sources, studies involving the endoscopic repair of CSF leaks were reviewed independently by 2 researchers. Studies included met the following criteria: full-text article written in the English language, at least 5 human patients undergoing purely endoscopic surgical repair of a CSF leak, and documented follow-up. Data extracted included leak etiology, presentation and location, the use of imaging, intrathecal fluorescein, and adjunctive measures as well as the success rate of the repair., Results: Fifty-five studies, involving 1778 fistulae repairs, were included for analysis. Spontaneous leaks were most prevalent, with the ethmoid roof and sphenoid the most common sites involved. The overall success rate of repair was high at 90% for primary and 97% for secondary repairs. A low complication rate of less than 0.03% was reported., Conclusion: The endoscopic repair of CSF fistula is both safe and effective and should be considered the standard of care for most cases. Evidence supporting adjunctive measures such as lumbar drains and antibiotics remains limited despite their common use.