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Mesenchymal stem cells have antifibrotic effects on transforming growth factor-beta1-stimulated vocal fold fibroblasts

Hiwatashi, Nao; Bing, Renjie; Kraja, Iv; Branski, Ryan C
OBJECTIVES/HYPOTHESIS: Mesenchymal stem cells (MSCs) hold therapeutic promise for vocal fold scar, yet the precise mechanism(s) underlying tissue level changes remain unclear. We hypothesize that MSCs interact with native fibroblasts to favorably affect healing. Furthermore, we hypothesize that these interactions vary based on MSC source. METHODS: Vocal fold fibroblasts (VFFs), adipose-derived stem cells, and bone marrow-derived stem cells (BMSCs) were extracted from Sprague-Dawley rats; and a coculture model was employed culturing VFFs +/- transforming growth factor (TGF-beta1) (10 ng/mL) +/- MSCs. Monoculture MSCs were also prepared as a control. Both extracellular matrix (ECM) and components of the TGF-beta signaling pathway were analyzed via polymerase chain reaction and western blotting. RESULTS: Significantly decreased TGF-beta1 mRNA and alpha-smooth muscle actin protein was observed in VFFs in response to TGF-beta1 in the coculture with both MSCs (P < 0.05, P < 0.01). BMSCs significantly downregulated collagen I (P < 0.05), collagen III (P < 0.05), Smad3 (P < 0.01), and TGF-beta1 receptor I (P < 0.01) mRNA in VFFs. Hyaluronic synthase-1 and 2 increased in cocultured BMSCs when compared with monocultured BMSCs at baseline and in response to TGF-beta1 (P < 0.01). CONCLUSION: MSCs had a favorable effect on ECM regulation as well as suppression of TGF-beta1 signaling in VFF. Bidirectional paracrine signaling was also observed as VFFs altered ECM regulation in MSCs. These data provide insight into the regenerative effects of MSCs and provide a foundation for clinical application. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016.
PMCID:5177483
PMID: 27345475
ISSN: 1531-4995
CID: 2166942

Expert consensus of general surgery residents' proficiency with common endocrine operations

Phitayakorn, Roy; Kelz, Rachel R; Petrusa, Emil; Sippel, Rebecca S; Sturgeon, Cord; Patel, Kepal N; Perrier, Nancy D
BACKGROUND: Proficiency with common endocrine operations is expected of graduating, general surgery residents. However, no expert consensus guidelines exist about these expectations. METHODS: Members of the American Association of Endocrine Surgeons were surveyed about their opinions on resident proficiency with common endocrine operations. RESULTS: Overall response rate was 38%. A total of 92% of the respondents operate with residents. On average, they believed that the steps of a total thyroidectomy for benign disease and a well-localized parathyroidectomy could be performed by a postgraduate year 4 surgery resident. Specific steps that they thought might require more training included decisions to divide the strap muscles or leaving a drain. Approximately 66% of respondents thought that a postgraduate year 5 surgery resident could independently perform a total thyroidectomy for benign disease, but only 45% felt similarly for malignant thyroid disease; 79% thought that a postgraduate year 5 surgery resident could independently perform a parathyroidectomy. Respondents' years of experience correlated with their opinions about resident autonomy for total thyroidectomy (benign r = 0.38, P < .001; malignant r = 0.29, P = .001) but not parathyroidectomy. On multivariate analysis, sex and years of experience of the respondents were independently associated with opinions on autonomy but only for total thyroidectomy for benign disease (P = .001). Annual endocrine volume of the respondents did not correlate with beliefs in autonomy. CONCLUSION: There was general agreement among responding members of the AAES about resident proficiency and autonomy with common endocrine operations. As postgraduate year 5 residents may not be proficient in advanced endocrine operations, opportunities exist to improve training prior to the transition to independent practice for graduates that anticipate performing endocrine operations routinely.
PMID: 27865597
ISSN: 1532-7361
CID: 2314272

A critical analysis of melanoma malpractice litigation: Should we biopsy everything?

Rayess, Hani M; Gupta, Amar; Svider, Peter F; Raza, S Naweed; Shkoukani, Mahdi; Zuliani, Giancarlo F; Carron, Michael A
OBJECTIVES/HYPOTHESIS:The aim of this study was to evaluate factors raised in malpractice litigation related to the diagnosis and management of melanoma and to further assess issues impacting outcome. STUDY DESIGN:Retrospective chart review. METHODS:The Westlaw legal database was searched for malpractice litigation resolved over the last 20 years relating to melanoma. Cases were evaluated for allegations, defendant specialty, outcome, and other issues raised. RESULTS:Of the 80 cases evaluated, 49% were resolved in the defendants' favor. In greater than 80% of cases, there was alleged misdiagnosis. In 35% of cases, the patient had expired secondary to melanoma at the time of litigation. There was no statistical difference in payments upon comparison of cases with and without mortality. A greater proportion of cases with dermatologists and pathologists as defendants involved alleged misdiagnosis. The most common locations for melanoma were the extremities and the head-and-neck region, at 32.5% and 22.5%, respectively. Location did not significantly impact the outcome of cases. CONCLUSION:Malpractice litigation relating to melanoma involves numerous physicians, including dermatologists, pathologists, and otolaryngologists. Alleged misdiagnosis of a pigmented lesion was the most common cause of litigation and involved physicians from numerous specialties. Patients who were misdiagnosed had a significantly higher likelihood of having active disease at the time of litigation. Ultimately improved methods of detecting concerning pigmented lesions need to be developed. Factors such as death and poor cosmetic outcome did not significantly impact litigation outcome. LEVEL OF EVIDENCE:NA Laryngoscope, 127:134-139, 2017.
PMID: 27480801
ISSN: 1531-4995
CID: 3217812

Pediatric rhinoplasty: A discussion of perioperative considerations and systematic review

Gupta, Amar; Svider, Peter F; Rayess, Hani; Sheyn, Anthony; Folbe, Adam J; Eloy, Jean Anderson; Zuliani, Giancarlo; Carron, Michael A
OBJECTIVES/OBJECTIVE:Pediatric rhinoplasty has traditionally raised numerous concerns, including its impact on growth as well as the psychological sequelae of undergoing a potentially appearance-altering procedure. Our objective was to critically evaluate available individual patient data relevant to pediatric rhinoplasty, and further discuss perioperative considerations. METHODS:A systematic review was conducted using PubMed/MEDLINE databases. Data extracted and analyzed from included studies included patient demographics, surgical indications, operative approaches, outcomes, complications, revision rates, and other clinical considerations. RESULTS:Seven studies encompassing 253 patients were included, with age ranging from 7 months to 19 years. Two-thirds of patients were male. 41.7% reported antecedent trauma, and common overall surgical indications included "functional aesthetic" (24.5%) followed by cleft lip nasal deformity (15.8%). The majority (79.1%) underwent open approaches, and 71.1% of patients underwent concomitant septal intervention. The most frequently used grafting materials were septal cartilage (52.8%) and conchal cartilage (16.5%). Surgical outcomes were heterogeneous among these studies. Complication rates were only specified in 5 of the 7 studies and totaled 57 patients (39.6%). Aesthetic dissatisfaction (11.8%) and postoperative nasal obstruction (5.6%) were the most commonly reported complications. Revisions were performed in 13.5%. CONCLUSION/CONCLUSIONS:Rhinoplasty is safe in the pediatric population, although revisions rates appear greater than those reported in adults. This study of 253 represents the largest pooled sample size to date; nonetheless, non-standardized outcome measures, minimal long-term followup data, and lack of discussion regarding psychological sequelae all contribute to the need for further high-quality studies evaluating this topic.
PMID: 28012510
ISSN: 1872-8464
CID: 3217832

Parallel processing by cortical inhibition enables context-dependent behavior

Kuchibhotla, Kishore V; Gill, Jonathan V; Lindsay, Grace W; Papadoyannis, Eleni S; Field, Rachel E; Sten, Tom A Hindmarsh; Miller, Kenneth D; Froemke, Robert C
Physical features of sensory stimuli are fixed, but sensory perception is context dependent. The precise mechanisms that govern contextual modulation remain unknown. Here, we trained mice to switch between two contexts: passively listening to pure tones and performing a recognition task for the same stimuli. Two-photon imaging showed that many excitatory neurons in auditory cortex were suppressed during behavior, while some cells became more active. Whole-cell recordings showed that excitatory inputs were affected only modestly by context, but inhibition was more sensitive, with PV+, SOM+, and VIP+ interneurons balancing inhibition and disinhibition within the network. Cholinergic modulation was involved in context switching, with cholinergic axons increasing activity during behavior and directly depolarizing inhibitory cells. Network modeling captured these findings, but only when modulation coincidently drove all three interneuron subtypes, ruling out either inhibition or disinhibition alone as sole mechanism for active engagement. Parallel processing of cholinergic modulation by cortical interneurons therefore enables context-dependent behavior.
PMCID:5191967
PMID: 27798631
ISSN: 1546-1726
CID: 2297142

Are industry financial ties associated with greater scholarly impact among academic otolaryngologists?

Svider, Peter F; Bobian, Michael; Lin, Ho-Sheng; Setzen, Michael; Baredes, Soly; Eloy, Jean Anderson; Folbe, Adam J
OBJECTIVES/HYPOTHESIS: In response to concerns regarding physician-industry relationships, the Physician Sunshine Act of 2010 was passed in an effort to increase transparency and accountability. Our objective was to determine whether there is an association between industry support and scholarly impact among academic otolaryngologists. METHODS: Faculty listings, academic rank, and fellowship training of academic otolaryngologists were accessed from departmental websites. H-indices, number of publications, and publication range (years) of each individual were calculated using the Scopus database. The Center for Medicare and Medicaid Services Open Payments database was used to determine industry payments during 2014 to each otolaryngologist. RESULTS: Of 1,515 otolaryngologists, 65.4% received industry support and 15.8% received support > $1,000. No difference in impact, as measured by the h-index, was noted upon comparison of those receiving support and those who did not (P > 0.05). Individuals receiving > $1,000 had higher h-indices and total publications than those receiving < $1,000 or receiving no support (H = 17.8 vs. 10.9, P < 0.0001), even upon controlling for academic seniority. Upon organization by subspecialty, individuals receiving > $1,000 had greater scholarly impact among most subspecialties. Industry contributions increased with advancing experience. CONCLUSION: Receiving industry contributions greater than $1,000 is associated with greater scholarly impact among academic otolaryngologists. In a smaller surgical specialty, such as otolaryngology-head and neck surgery, direct industry research support-as well as indirect contributions through the support of educational programs, consulting, and other expenses-potentially impacts scholarly discourse; these findings do not reflect a causal relationship and may require further characterization. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016.
PMID: 27114324
ISSN: 1531-4995
CID: 2092432

Physiologic and Acoustic Effects of Opera Performance

Kwak, Paul E; Stasney, C Richard; Hathway, Jeremy R; Guffey, Danielle; Minard, Charles G; Ongkasuwan, Julina
INTRODUCTION/HYPOTHESIS: Opera performance is physiological and emotional, and singing performers utilize their larynges in often strenuous ways. Historically, the training of a classical voice has been considered the paragon of healthy singing. However, the natural history of a performing larynx has not been studied systematically. There is paucity of scientific studies to guide practice patterns, particularly with regard to the course and extent of post-performance physiologic and acoustic changes. STUDY DESIGN: A prospective case series was carried out. METHODS: Principal singers in the Houston Grand Opera's 2012-2013 repertory were enlisted, for a total of seven singers. Stroboscopy was performed prior to the start of rehearsals, and at the completion of the opera's run. Data points included erythema, edema, masses or lesions, mucosal waveform, supraglottic posture; acoustic measurements were also performed. RESULTS: There were statistically significant differences (P < 0.05) in the mucosal wave on pre- and postperformance stroboscopic examinations. Acoustical measures did not achieve statistical significance, but there was a trend toward increased harmonic-to-noise ratio in postperformance measures, as well as decreased frequency range and reading F0. Measures of intra- and inter-rater reliability indicated varying levels of intra-rater reliability, and generally poor inter-rater reliability. CONCLUSIONS: This pilot study describes physiologic and acoustic changes that may occur over the course of a series of rehearsals and performances in the operatic larynx. In so doing, it highlights a need for larger studies with increased frequency of serial examinations to study in a systematized way what may be natural reactive changes that occur during performance.
PMID: 27208902
ISSN: 1873-4588
CID: 2385602

Spontaneous Iliopsoas Hematoma following Microvascular Free Tissue Transfer

Markey, Jeffrey D; Alemi, A Sean; Naunheim, Margaret L; Faden, Daniel L; Heaton, Chase M; Seth, Rahul
Spontaneous hematoma within the iliopsoas muscle (SIH) is a rare complication most commonly seen in coagulopathic patients. Often, patients undergoing microvascular free tissue transfer are anticoagulated for anastomotic patency. Here we describe two cases of postoperative SIH following contralateral anterolateral thigh (ALT) free tissue transfer for reconstruction of oncologic head and neck defects. Both patients described hip pain after mobilization and had a corresponding acute blood loss anemia. Diagnosis of SIH was confirmed by CT and both patients were managed conservatively. Given that anticoagulation is a common practice following head and neck free tissue transfer, surgeons should be aware of this potential complication.
PMCID:5425841
PMID: 28536664
ISSN: 2090-6765
CID: 2718812

Localized Proteomics of Individual Neurons Isolated from Formalin-Fixed, Paraffin-Embedded Tissue Sections Using Laser Capture Microdissection

Drummond, Eleanor; Nayak, Shruti; Ueberheide, Beatrix; Wisniewski, Thomas
ISI:000429058300020
ISSN: 0893-2336
CID: 4706692

Treatment of the Mal de Debarquement Syndrome: A 1-Year Follow-up

Dai, Mingjia; Cohen, Bernard; Cho, Catherine; Shin, Susan; Yakushin, Sergei B
The mal de debarquement syndrome (MdDS) is a movement disorder, occurring predominantly in women, is most often induced by passive transport on water or in the air (classic MdDS), or can occur spontaneously. MdDS likely originates in the vestibular system and is unfamiliar to many physicians. The first successful treatment was devised by Dai et al. (1), and over 330 MdDS patients have now been treated. Here, we report the outcomes of 141 patients (122 females and 19 males) treated 1 year or more ago. We examine the patient's rocking frequency, body drifting, and nystagmus. The patients are then treated according to these findings for 4-5 days. During treatment, patients' heads were rolled while watching a rotating full-field visual surround (1). Their symptom severity after the initial treatment and at the follow-up was assessed using a subjective 10-point scale. Objective measures, taken before and at the end of the week of treatment, included static posturography. Significant improvement was a reduction in symptom severity by more than 50%. Objective measures were not possible during the follow-up because of the wide geographic distribution of the patients. The treatment group consisted of 120 classic and 21 spontaneous MdDS patients. The initial rate of significant improvement after a week of treatment was 78% in classic and 48% in spontaneous patients. One year later, significant improvement was maintained in 52% of classic and 48% of spontaneous subjects. There was complete remission of symptoms in 27% (32) of classic and 19% (4) of spontaneous patients. Although about half of them did not achieve a 50% improvement, most reported fewer and milder symptoms than before. The success of the treatment was generally inversely correlated with the duration of the MdDS symptoms and with the patients' ages. Prolonged travel by air or car on the way home most likely contributed to the symptomatic reversion from the initial successful treatment. Our results indicate that early diagnosis and treatment can significantly improve results, and the prevention of symptomatic reversion will increase the long-term benefit in this disabling disorder.
PMCID:5418223
PMID: 28529496
ISSN: 1664-2295
CID: 2572212