The single-stage melolabial flap for internal lining of full thickness defects of the nasal ala.

BACKGROUND: Full-thickness defects of the nasal ala necessitate composite repair of the nasal lining, cartilage and soft tissue envelope. Repair of the nasal lining is particularly challenging due to access and geometry of this area. OBJECTIVE: To evaluate the melolabial flap as a single stage operation for repair of full-thickness nasal ala defects. METHODS: Retrospective study of seven adult patients with full-thickness nasal ala defects who underwent melolabial flap repair. Complications and operative technique were recorded and described. RESULTS: Of the seven patients who underwent melolabial flap repair, each had excellent coverage of the defect postoperatively. There were two cases of mild ipsilateral congestion, and no revision procedures performed. CONCLUSION: The melolabial flap is a versatile reconstructive option for repair of the internal lining of the nasal ala, and in our series there were no significant complications or revision procedures performed.

The effect of perichondrium on cartilage graft properties.

PURPOSE OF REVIEW: The role of perichondrium in cartilage graft survival has been long debated. Although the innate function of perichondrium in providing mechanical and regenerative support to cartilage in its native position is relatively undisputed, studies continue to vacillate over how the perichondrium effects cartilage grafts once transplanted. This review evaluates historical and recent experiments showing how perichondrium may or may not impact graft survival. RECENT FINDINGS: Experimental studies in animal models have more recently evaluated macroscopic and microscopic properties of diced cartilage grafts with and without perichondrium, finding that in general grafted cartilage with perichondrial components retains greater weight and mechanical strength compared with cartilage without perichondrial components. However, these findings have not been replicated in humans. Solid pieces of rib cartilage have most recently been used without perichondrium to prevent warping, though no studies have evaluated whether retaining perichondrium with oblique and concentric cutting techniques may effect overall resorption. SUMMARY: Although historical opinions and more recent animal studies suggest a role of perichondrium in cartilage graft survival, randomized controlled human studies are still lacking on whether retaining perichondrium truly effects graft survival and ultimate surgical outcomes.

Treatment of the Crooked Nose.

The crooked nose is a challenging esthetic and functional problem. The surgeon must carefully evaluate baseline facial asymmetry as well as whether deviation stems from the upper third, middle third, or lower third of the nose. Surgical intervention should be tailored accordingly, with techniques geared toward addressing each deviated section. Modified dorsal preservation techniques represent a newer means to address deviations. Operative results must be measured, ideally through patient-reported outcomes measures, to quantify overall success.

Factors Associated with Ocular Injury in Orbital Fracture Patients: Who Requires Urgent Ophthalmic Evaluation?

Importance: Create validated criteria to identify orbital fracture patients at higher risk for significant ocular injuries. Objective: Determine history and physical examination findings in orbital fracture patients who are associated with ocular injury and warrant urgent assessment by an ophthalmologist. Design, Setting, and Participants: Retrospective chart review of 535 adult orbital fracture patients evaluated at a Level I emergency department between 2014 and 2017, without prior history of orbital fracture, ocular injury, or ocular/orbital surgery. Main Outcomes and Measure: Presence of ocular injury. Results: In total, 195 (36%) patients had an ocular injury. Those with and without ocular injury were compared in a multivariate logistic regression model including demographics, fracture characteristics, injury mechanism, and physical examination findings. Visual acuity change, radiographic retrobulbar hemorrhage, abnormal pupillary reaction, and inability to open the injured eye all had significant associations with ocular injury when other findings were controlled. Conclusion: This study shows a significant association between ocular injury and visual acuity change, retrobulbar hemorrhage, abnormal pupillary reaction, and inability to open the injured eye. These factors can help triage when to obtain an urgent ophthalmology consult.

Quantifying Eye Alignment in Orbital Fracture Patients: The Digital Hess Screen.

Background: Quantifying diplopia to determine management and track outcomes for orbital fracture patients is vital for standardization between visits, physicians, and coordination among the multiple specialties that manage these patients. However, standardization is challenging, as diplopia is often reported subjectively. This study sought to describe the utility of the digital Hess screen in patients with orbital fractures compared with a control group. Materials and Methods: A prospective pilot study was designed in which adult patients who presented with orbital fractures between November 2017 and January 2019 without prior history of orbital pathology were recruited. Subjects underwent digital Hess screen testing, in which they wore anaglyph glasses and aligned targets on a computer screen to quantify static eye alignment. The degree of any eye misalignment was analyzed and compared with controls. Results: Ninety-one patients and 35 controls were enrolled. All participants were able to complete the digital Hess screen. Average cumulative deviation score of orbital fracture patients within 1 month of injury was 0.65°, compared with 0.28° in controls. This was a statistically significant difference (p < 0.01, 95% confidence interval -0.18 to 0.18). Conclusion: The Hess screen has been used to quantify phoria as a correlate of eye alignment and diplopia, but older versions were cumbersome and difficult to analyze. This study is the first to report on using the digital Hess screen to quantify phoria in orbital fracture patients and provides a more concise and standardized means to track clinical and surgical outcomes of eye alignment.

The current practice of open neck mass biopsy in the diagnosis of head and neck cancer: A retrospective cohort study.

OBJECTIVE: To characterize current use of open neck mass biopsy for diagnosis of squamous cell carcinoma in patients presenting with a neck mass. METHODS: Using the University of Michigan Specialized Program of Research Excellence in Head and Neck Cancer patient database (2008-2014), we reviewed patients' referral documentation to identify those who received open neck mass biopsies as part of their squamous cell carcinoma diagnosis. We compared subsequent treatment between patients who did and did not receive an open neck mass biopsy. RESULTS: Of 940 patients, 50 patients had received open neck mass biopsy leading to squamous cell carcinoma diagnosis. Only 19 of 50 patients (38%) had undergone fine-needle aspiration prior to open neck mass biopsy. There were no statistically significant differences in treatment or outcomes between patients who did and those who did not receive open neck mass biopsy. CONCLUSION: Optimal care for patients who present with a neck mass is fine-needle aspiration. Unfortunately, these data show that many patients undergo open neck mass biopsy for diagnosis, often without prior fine-needle aspirate. Compared to fine-needle aspiration, open biopsy incurs additional risks of general anesthesia and greater surgical risks. While our data did not find statistically significant differences between treatment offered and outcomes, this small study was not expected to demonstrate a difference in outcomes. Further work is needed to promote the utility of fine-needle aspiration for diagnosis of neck mass and to discourage use of open neck mass biopsy as a primary diagnostic intervention. LEVEL OF EVIDENCE: 2c (Outcomes Research).

Is There a Difference in Staging and Treatment of Head and Neck Squamous Cell Tumors Between Tertiary Care and Community-Based Institutions?

OBJECTIVE: To characterize the differences in the staging and treatment of patients with head and neck squamous cell carcinoma between a tertiary care center and community-based practices. METHODS: This study is a retrospective chart review of 943 adult patients with head and neck squamous cell cancer presenting to a tertiary care center between 2008 and 2014 as part of the University of Michigan Head and Neck Cancer Specialized Program of Research Excellence (UM HN-SPORE) database. Demographic information, diagnostic testing, staging information, and treatment recommendations were recorded. RESULTS: Of 943 patients reviewed, 159 had documentation of tumor stage that was assigned by the community-based practice. Of these, 53% had a tumor staging change made at the tertiary care center, with 43% of patients upstaged and 10% of patients downstaged. Fifty-one percent received different treatment than had previously been offered at the community-based practice, although only 31% of these patients had a change in tumor staging. CONCLUSION: Over half of patients with head and neck squamous cell carcinoma who are evaluated at a tertiary care center after the initial evaluation at a community-based practice have their tumors staged differently, with the majority upstaged. A significant number of these patients also received different treatment than was initially offered at the referring practice. Future studies are required to determine whether these differences have an effect on tumor recurrence and patient survival rates. LEVEL OF EVIDENCE: 2c (Outcomes Research).

Does drug induced sleep endoscopy-directed surgery improve polysomnography measures in children with Down Syndrome and obstructive sleep apnea?

BACKGROUND: Children with Down Syndrome (DS) and obstructive sleep apnea (OSA) are difficult to treat, as first line therapies may not lead to significant improvement. Drug-induced sleep endoscopy (DISE) directed surgery may be particularly beneficial for these patients. OBJECTIVE: To assess change in polysomnography (PSG) measures of patients with DS who underwent DISE-directed surgery. METHODS: Retrospective chart review was performed on patients with DS who underwent DISE-directed surgery and had pre- and post-surgery PSG. Patients were analyzed in groups defined by previous adenotonsillectomy. Two-sided t-tests with equal variances were used to assess statistical significance. RESULTS: Of 24 patients reviewed, 14 were surgically naïve and 10 had undergone prior adenotonsillectomy. The primary outcome was change in PSG parameters including apnea hypopnea index, obstructive apnea hypopnea index, oxygen nadir, oxygen desaturation index, and mean carbon dioxide level. While improvement was seen in all PSG parameters, only improvement in oxygen nadir in children who had undergone prior adenotonsillectomy was statistically significant (88.5% to 90.9%, p = .04). CONCLUSIONS AND SIGNIFICANCE: DISE-directed surgery may be beneficial for children with DS and OSA, with improvement in the means of main PSG measures observed. A larger, prospective study is warranted to further explore DISE utility.

Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor.

HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs. A humanized mouse model of HIV infection demonstrated that T cells expressing optimized CARs were superior at expanding in response to antigen, protecting CD4 T cells from infection, and reducing viral loads compared to T cells expressing the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled HIV spread after ART removal better than analogous CAR T cells containing the CD28 costimulatory domain. Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy.

Complications in facial Mohs defect reconstruction.

PURPOSE OF REVIEW: To review the recent literature in regards to complications after reconstruction of Mohs defects, outline common pitfalls and to discuss the literature on avoiding complications as outlined per aesthetic subunit. RECENT FINDINGS: Complications in facial Mohs reconstruction commonly consist of infection, wound necrosis and dehiscence, hematoma and suboptimal scarring. However, site-specific complications such as hairline or eyebrow distortion, eyelid retraction or ectropion, nasal contour abnormality, alar retraction, nasal valve compromise, significant facial asymmetry or even oral incompetence must also be considered. SUMMARY: A successful reconstruction mimics the premorbid state and maintains function. The use of perioperative antibiotics, sterile technique, meticulous hemostasis, subcutaneous dissection and deep sutures to minimize wound tension should be considered for all Mohs reconstructions. Cartilage grafting can minimize nasal deformity and obstruction. Reconstruction near the lower eyelid should employ periosteal suspension sutures to minimize downward tension and lid retraction. Perioral complications, such as microstomia and oral incompetence, typically improve with time and therapy. Always consider secondary procedures such as dermabrasion, steroid injection, scar revision and laser resurfacing to help optimize aesthetic outcome.

A humanized mouse model for HIV-2 infection and efficacy testing of a single-pill triple-drug combination anti-retroviral therapy.

While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, TriumeqR). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis. Oral drug treatment led to full viral suppression and protection from CD4 T cell depletion. Cessation of therapy resulted in viral rebound and CD4 T cell loss. These proof-of-concept studies establish the utility of hu-mice for evaluating HIV-2 pathogenesis in more detail in the future, testing novel therapies and providing pre-clinical efficacy data of a three drug combination to treat HIV-2 infections.

Academic institution pilot study shows far fewer diagnoses of sinusitis than reported nationally.

OBJECTIVE: To compare the prevalence of acute sinusitis (AS) and chronic sinusitis (CS) diagnosed by primary care and emergency medicine physicians in our academic institution to national data. STUDY DESIGN: Cross-sectional pilot study of institutional census data and a population-based national sample. The setting was primary care and emergency departments at an academic healthcare institution and community healthcare practices nationally. MATERIALS AND METHODS: We determined the proportion of adults visits at our institution for AS and CS from January 1, 2005, to December 31, 2010. We used the same parameters with the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. As a control comparison, we determined the proportion of visits for epistaxis. RESULTS: The sinusitis prevalence was considerably lower at our academic institution: all sinusitis (AS and CS combined) ranged from 0.8% to 1.0% at our institution compared to 3.1% to 3.7% nationally. There were very small differences between AS rates at the academic institution (0.7%-0.8%) and nationally (0.8%-1.4%, P < 0.001) but very large differences between CS rates at the academic institution (0.1%) and national data (1.7%-2.9%, P < 0.001). Epistaxis rates were nearly identical in both datasets (0.1%-0.2%, P = 0.98-0.99). CONCLUSION: The prevalence of CS is much lower at our academic institution, but the prevalence of AS and epistaxis are similar to national data. This suggests CS is over-diagnosed by primary care and emergency medicine providers and that CS diagnosed outside of an academic institution or a specialty clinic may not hold up to diagnostic scrutiny. For this reason, diagnostic and treatment protocols for CS that have been developed in academic specialty clinics should not be extrapolated to patients diagnosed with CS in the community setting. The most appropriate intervention for the majority of patients diagnosed with CS in primary care and emergency medicine may be education of providers and patients about conditions that may be misdiagnosed as CS.

Complication Rates in Delayed Reconstruction of the Head and Neck After Mohs Micrographic Surgery.

IMPORTANCE: Same-day Mohs reconstructive surgery is not always possible owing to patient factors, scheduling, and complexity of defect, but there is hesitancy in delaying closure of such defects. OBJECTIVE: To describe the frequency of and predictors of complications in patients undergoing delayed facial reconstruction after Mohs micrographic surgery (MMS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, multi-institutional cohort study from February 1, 1989, to December 31, 2012. Data were pooled from 2 institutions: University of Washington Medical Center and Virginia Mason Medical Center. All patients who underwent MMS for facial carcinomas with delayed (non-same-day) reconstruction were included. We excluded those with incomplete medical records and no follow-up. The analysis was performed from June 2014 to March 2016. MAIN OUTCOMES AND MEASURES: Our main outcome measure was postoperative complication, classified as immediate (≤24 hours after surgery) or delayed (>24 hours after surgery). RESULTS: A total of 415 cases in 342 patients were identified. Reconstruction occurred from 1 to 11 days after excision, with 95.4% of repairs occurring within 2 days of MMS. The overall complication rate was 8.2%. The total delayed complication rate was 7.7% (32 of 415 cases). The overall infection rate was 2.4%. In terms of patient characteristics, reconstruction delayed more than 2 days, bone or cartilage exposure, and large defects were associated with complications. In terms of defect location and reconstruction type, complications were associated with composite defects (those that included >1 facial subunit) and use of interpolated flaps with cartilage grafting. We used these variables in a multivariable logistic regression model and found that composite location, use of interpolated flap with cartilage grafting, and reconstruction delayed more than 2 days were associated with postoperative complications. Among the variables in the model, composite location of defects, interpolated flap with cartilage grafting, and delayed reconstruction greater than 2 days were found to have a statistically significant association with a complication (OR, 3.48 [95% CI, 1.16-10.56]; OR, 4.93 [95% CI, 1.44-16.95]; OR, 4.26 [95% CI, 1.24-14.60], respectively). CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest study to report complication rates in delayed reconstruction of MMS defects in the head and neck, noting a rate that is similar to what has been reported in the literature. We noted a statistically significant increased risk of complications when reconstruction is performed for composite defects, if an interpolated flap with cartilage is performed, and if reconstruction is performed after more than 2 days. LEVEL OF EVIDENCE: 3.

A diagnostic dilemma: chronic sinusitis diagnosed by non-otolaryngologists.

BACKGROUND: Ambulatory care visits for chronic sinusitis outnumber visits for acute sinusitis. The majority of these visits are with non-otolaryngologists. In order to better understand patients diagnosed with chronic sinusitis by non-otolaryngologists, we sought to determine if incident cases of chronic sinusitis diagnosed by primary care (PC) or emergency medicine (EM) providers meet diagnostic criteria. METHODS: This was a retrospective cohort study. Patients were identified using administrative data from 2005 to 2006. The dataset was then clinically annotated based on chart review. We excluded prevalent cases. RESULTS: We identified 114 patients with newly diagnosed chronic sinusitis in EM (75) or PC settings (39). Rhinorrhea (EM 61%, PC 59%) and nasal obstruction (EM 67%, PC 64%) were common in both settings but facial fullness (EM 80%, PC 39%) and pain (EM 40%, PC 18%) were more common in the EM setting. Few patients reported symptoms of 90 days or longer (EM 6.0%, PC 24%) and no patient had evidence of inflammation on physical examination. A minority of patients received a sinus computed tomography (CT) scan (22.8%) or nasal endoscopy (1.8%). In total, only 1 patient diagnosed with chronic sinusitis met the diagnostic criteria. CONCLUSION: Most patients diagnosed with chronic sinusitis by non-otolaryngologists do not have the condition. Caution should be used in studying chronic sinusitis using administrative data from non-otolaryngology providers because a large proportion of the patients may not actually have the disease.

Diagnosis and treatment of acute sinusitis in the primary care setting: A retrospective cohort.

OBJECTIVES AND HYPOTHESIS: Our objectives were to characterize the quality of acute sinusitis care and to identify nonclinical factors associated with antibiotic use for acute sinusitis. We hypothesized that we would identify provider-level factors associated with antibiotic use. STUDY DESIGN: Retrospective cohort at a single academic institution. METHODS: We developed and clinically annotated an administrative dataset of adult patients diagnosed with acute sinusitis between January 1, 2005, and December 31, 2006. We used identify factors associated with receipt of antibiotics. RESULTS: We find that 66.0% of patients with mild symptoms of short duration are given antibiotics, and that nonclinical factors, including the individual provider, the provider's specialty, and the presence of a medical trainee, significantly influence antibiotic use. Relative to internal medicine providers, family medicine providers use fewer antibiotics, and emergency medicine providers use more antibiotics for acute sinusitis. CONCLUSIONS: Antibiotics continue to be overused for patients with mild acute sinusitis of short duration. Nonclinical characteristics, including the individual provider, the provider's specialty, and the presence of a medical trainee, significantly influence use of antibiotics for acute sinusitis. LEVEL OF EVIDENCE: 4.

Humanized Rag1-/- γc-/- mice support multilineage hematopoiesis and are susceptible to HIV-1 infection via systemic and vaginal routes.

Several new immunodeficient mouse models for human cell engraftment have recently been introduced that include the Rag2(-/-)γc(-/-), NOD/SCID, NOD/SCIDγc(-/-) and NOD/SCIDß2m(-/-) strains. Transplantation of these mice with CD34(+) human hematopoietic stem cells leads to prolonged engraftment, multilineage hematopoiesis and the capacity to generate human immune responses against a variety of antigens. However, the various mouse strains used and different methods of engrafting human cells are beginning to illustrate strain specific variations in engraftment levels, duration and longevity of mouse life span. In these proof-of-concept studies we evaluated the Balb/c-Rag1(-/-)γ(-/-) strain for engraftment by human fetal liver derived CD34(+) hematopoietic cells using the same protocol found to be effective for Balb/c-Rag2(-/-)γc(-/-) mice. We demonstrate that these mice can be efficiently engrafted and show multilineage human hematopoiesis with human cells populating different lymphoid organs. Generation of human cells continues beyond a year and production of human immunoglobulins is noted. Infection with HIV-1 leads to chronic viremia with a resultant CD4 T cell loss. To mimic the predominant sexual viral transmission, we challenged humanized Rag1(-/-)γc(-/-) mice with HIV-1 via vaginal route which also resulted in chronic viremia and helper T cell loss. Thus these mice can be further exploited for studying human pathogens that infect the human hematopoietic system in an in vivo setting.

Humanized Rag2(-/-)gammac(-/-) (RAG-hu) mice can sustain long-term chronic HIV-1 infection lasting more than a year.

HIV-1 infection is characterized by life-long viral persistence and continued decline of helper CD4 T cells. The new generation of humanized mouse models that encompass RAG-hu, hNOG and BLT mice have been shown to be susceptible to HIV-1 infection and display CD4 T cell loss. Productive infection has been demonstrated with both R5 and X4 tropic strains of HIV-1 via direct injection as well as mucosal exposure. However the duration of infection in these mice was evaluated for a limited time lasting only weeks post infection, and it is not established how long the viremia can be sustained, and if the CD4 T cell loss persists throughout the life of the infected humanized mice. In the present study we followed the HIV-1 infected RAG-hu mice to determine the long-term viral persistence and CD4 T cell levels. Our results showed that viremia persists life-long lasting for more than a year, and that CD4 T cell levels display a continuous declining trend as seen in the human. These studies provide a chronic HIV-1 infection humanized mouse model that can be used to dissect viral latency, long-term drug evaluation and immune-based therapies.

Mucosal transmission of R5 and X4 tropic HIV-1 via vaginal and rectal routes in humanized Rag2-/- gammac -/- (RAG-hu) mice.

Studies on HIV-1 mucosal transmission to evaluate early events in pathogenesis and the development of effective preventive/prophylactic methods have thus far been hampered by the lack of a suitable animal model susceptible to HIV-1 infection by either vaginal and/or rectal routes. In this regard, while primate-SIV/SHIV and cat-FIV models provided useful surrogate platforms to derive comparative data, these viruses are distinct and different from that of HIV-1. Therefore an optimal model that permits direct study of HIV-1 transmission via mucosal routes is highly desirable. The new generation of humanized NOD/SCID BLT, NOD/SCIDgammac(-/-), and Rag2(-/-)gammac(-/-) mouse models show great promise to achieve this goal. Here, we show that humanized Rag2(-/-)gammac(-/-) mice (RAG-hu) engrafted with CD34 hematopoietic progenitor cells harbor HIV-1-susceptible human cells in the rectal and vaginal mucosa and are susceptible to HIV-1 infection when exposed to cell-free HIV-1 either via vagina or rectum. Infection could be established without any prior hormonal conditioning or mucosal abrasion. Both R5 and X4 tropic viruses were capable of mucosal infection resulting in viremia and associated helper T cell depletion. There was systemic spread of the virus with infected cells detected in different organs including the intestinal mucosa. R5 virus was highly efficient in mucosal transmission by both routes whereas X4 virus was relatively less efficient in causing infection. HIV-1 infection of RAG-hu mice by vaginal and rectal routes as shown here represents the first in vivo model of HIV-1 transmission across intact mucosal barriers and as such may prove very useful for studying early events in HIV-1 pathogenesis in vivo, as well as the testing of microbicides, anti-HIV vaccines/therapeutics, and other novel strategies to prevent HIV-1 transmission.