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Supplementary Figure Legend from Melanocyte Expression of Survivin Promotes Development and Metastasis of UV-Induced Melanoma in HGF-Transgenic Mice

We previously found the apoptosis inhibitor Survivin to be expressed in melanocytic nevi and melanoma but not in normal melanocytes. To investigate the role of Survivin in melanoma development and progression, we examined the consequences of forced Survivin expression in melanocytes in vivo. Transgenic (Tg) mouse lines (Dct-Survivin) were generated with melanocyte-specific expression of Survivin, and melanocytes grown from Dct-Survivin mice expressed Survivin. Dct-Survivin melanocytes exhibited decreased susceptibility to UV-induced apoptosis but no difference in proliferative capacity compared with melanocytes derived from non-Tg littermates. Induction of nevi in Dct-Survivin and non-Tg mice by topical application of 7,12-dimethylbenz(a)anthracene did not reveal significant differences in lesion onset (median, 10 weeks) or density (4 lesions per mouse after 15 weeks). Dct-Survivin mice were bred with melanoma-prone MH19/HGF-B6 Tg mice, and all progeny expressing either individual, neither, or both (Survivin/HGF) transgenes were UV-treated as neonates and then monitored for 43 weeks. Melanocytes in neonatal Survivin+/HGF+ mouse skin were less susceptible to UV-induced apoptosis than those from Survivin−/HGF+ mice. Onset of melanocytic tumors was earlier (median, 18 versus 24 weeks; P = 0.01, log-rank test), and overall tumor density was greater (7.7 versus 5.2 tumors per mouse; P = 0.04) in Survivin+/HGF+ compared with Survivin−/HGF+ mice. Strikingly, melanomas arising in Survivin+/HGF+ mice showed a greater tendency for lymph node (35% versus 0%; P = 0.04) and lung (53% versus 22%) metastasis and lower rates of spontaneous apoptosis than those in Survivin−/HGF+ mice. These studies show a role for Survivin in promoting both early and late events of UV-induced melanoma development in vivo. [Cancer Res 2007;67(11):5172–8]

Supplementary Figure 1 from Melanocyte Expression of Survivin Promotes Development and Metastasis of UV-Induced Melanoma in HGF-Transgenic Mice

To determine whether patients have improved quality of life outcomes with percutaneous bone conduction implant (p-BCI) versus transcutaneous bone conduction implant (t-BCI).Retrospective chart review of patients who have undergone placement of a BCI in the Ascension St John Providence Health System from 2013 to 2018. Patient satisfaction of t-BCI and p-BCI was measured using a questionnaire that incorporated the Glasgow Benefit Inventory (GBI) and BAHA, aesthetic, hygieneuse (BAHU) survey. Key outcome variables were separated into 2 categories: (1) evaluation of wound healing and implant-associated complications, and (2) quality of life improvements.Comparative analysis of the 27 p-BCI patients and 10 t-BCI patients showed overall positive benefit with no statistically significant difference on quality of life improvement between the two groups. Total complication rates for p-BCI (48.1 %) vs t-BCI (10 %) was marginally significant (p = 0.056). Rate of revision for p-BCI versus t-BCI was 14.8 % vs 0 %, respectively.This study provides a much-needed comparative insight in patient's experience with these two devices. Understanding which device is preferable in the patient's view will offer helpful information for guiding proper implant selection.

Calcinosis cutis describes a condition of pathologic calcium deposition in the dermis. Several subtypes exist, including the subepidermal calcified nodule. The oral mucosal calcified nodule (OMCN) was posited in 1992 as a specific term for a subepidermal calcified nodule occurring in the oral cavity, and since that time only six such lesions have been described in the literature. This report explores a case of OMCN on the palate of a 3-month-old infant with the goal of supplementing extant literature, providing a consideration of the differentials of palatal lesions in the pediatric population, and describing a unique instance in which OMCN resulted in a full-thickness defect requiring palatoplasty for repair.

Objectives Quantify number of MRI scans obtained in a tertiary neurotology practice and identify likelihood of pathologic findings. Study design Retrospective cohort study. Setting Tertiary neurotology center. Subjects and methods A retrospective analysis of all adult patients over 20 months (3/2012–10/2013) where MRI was deemed necessary for evaluation of neurotologic complaints. Demographics, clinical history, physical examination, and audiometric findings were used to categorize new patients into 7 groups: definite Meniere's disease (MD), probable MD, possible MD, vague dizziness, tinnitus only, asymmetric hearing loss (HL), and other symptoms to stratify risk for retrocochlear tumor and other relevant pathology. Results 1537 MRI scans were performed, 932 of these were for a new diagnosis. Discovering retrocochlear tumors was rare (1.4%). Patients with HL had a 0.3% (1/314) chance of retrocochlear tumor and 3.2% (10/314) chance of relevant pathology. Patients with only unilateral tinnitus had no evidence of retrocochlear tumors, and 3.8% chance of finding relevant pathology. Patients with “definite” or “probable” MD had no evidence of retrocochlear tumor or other relevant findings. All discovered acoustic neuromas were in the “possible MD” category, which had a 9.3% chance of finding all relevant pathology. Conclusions In a tertiary neurotology center, the likelihood of finding a retrocochlear tumor on MRI is rare. In the current study, unilateral tinnitus exclusively, “definite MD,” and “probable MD” failed to yield a single example of retrocochlear tumor. Patients with “possible MD” had the highest probability of finding retrocochlear tumors and other relevant pathology.

Importance Obtaining sufficient operating room time for inpatient consults requiring an operative intervention is a persistent challenge for otolaryngologists. Objective To examine the institution of an otolaryngology-specific operating room (OR) for unscheduled (add-on) cases for its association with time from initial consultation to surgery and, secondarily, to determine utilization of a dedicated block of time. Design, Setting, and Participants Retrospective review of medical records of a tertiary care pediatric hospital for patients treated between January 1, 2015, and March 31, 2016; analysis was concluded by June 2016. Included were all patients undergoing inpatient otolaryngology consultations who required nonemergency operative procedures. Interventions In August 2015, a once-weekly 5-hour block of OR time dedicated to inpatient otolaryngology consults was instituted. Prior to this, cases were placed on an add-on list shared between all surgical services. Main Outcomes and Measures It was hypothesized that institution of a dedicated block of OR time would decrease the time from initial consultation to operative intervention and would be utilized at a high rate. Operating room utilization was calculated by dividing scheduled OR time by actual OR time utilized. Time from initial consultation to OR intervention was compared before and after the institution of the dedicated OR block. Results A total of 316 inpatient add-on pediatric cases (including 108 patients from the intensive care unit [ICU]) were scheduled during the study period. The most common cases were microlaryngoscopy/bronchoscopy (79%) and tracheostomy (8%). Mean (SD) time between consultation and OR intervention was 7.8 (1.6) days prior to establishing the add-on OR and 4.4 (1.3) days after it was established (absolute difference of 3.4 days; 95% CI, 3.1-3.7 days). Mean (SD) time between consultation and OR intervention was 7.4 (5.0) days for ICU patients prior to intervention and 5.6 (3.0) days after intervention (absolute difference of 1.8 days; 95% CI, 1.6-2.0 days). Total utilization of the OR block time was 74%, and adjusted utilization was 86%. There was a 15% drop in the number of unscheduled add-on cases after the intervention (from 10 cases/mo to 8.5 cases/mo; absolute difference of 1.5 cases; 95% CI, 1.1-1.9 cases). Conclusions and Relevance Instituting a dedicated otolaryngology add-on OR was associated with significantly reduced time between initial consultation and operative care, by approximately 3 days, decreased the number of unscheduled add-on cases, and was utilized at a high level.

Purpose: UV radiation is the major environmental risk factor for melanoma and a potent inducer of oxidative stress, which is implicated in the pathogenesis of several malignancies. We evaluated whether the thiol antioxidant N-acetylcysteine (NAC) could protect melanocytes from UV-induced oxidative stress/damage in vitro and from UV-induced melanoma in vivo.Experimental Design: In vitro experiments used the mouse melanocyte line melan-a. For in vivo experiments, mice transgenic for hepatocyte growth factor and survivin, shown previously to develop melanoma following a single neonatal dose of UV irradiation, were given NAC (7 mg/mL; mother's drinking water) transplacentally and through nursing until 2 weeks after birth.Results: NAC (1-10 mmol/L) protected melan-a cells from several UV-induced oxidative sequelae, including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine, and depletion of free reduced thiols (primarily glutathione). Delivery of NAC reduced thiol depletion and blocked formation of 8-oxoguanine in mouse skin following neonatal UV treatment. Mean onset of UV-induced melanocytic tumors was significantly delayed in NAC-treated compared with control mice (21 versus 14 weeks; P = 0.0003).Conclusions: Our data highlight the potential importance of oxidative stress in the pathogenesis of melanoma and suggest that NAC may be useful as a chemopreventive agent.

We previously found the apoptosis inhibitor Survivin to be expressed in melanocytic nevi and melanoma but not in normal melanocytes. To investigate the role of Survivin in melanoma development and progression, we examined the consequences of forced Survivin expression in melanocytes in vivo. Transgenic (Tg) mouse lines (Dct-Survivin) were generated with melanocyte-specific expression of Survivin, and melanocytes grown from Dct-Survivin mice expressed Survivin. Dct-Survivin melanocytes exhibited decreased susceptibility to UV-induced apoptosis but no difference in proliferative capacity compared with melanocytes derived from non-Tg littermates. Induction of nevi in Dct-Survivin and non-Tg mice by topical application of 7,12-dimethylbenz(a)anthracene did not reveal significant differences in lesion onset (median, 10 weeks) or density (4 lesions per mouse after 15 weeks). Dct-Survivin mice were bred with melanoma-prone MH19/HGF-B6 Tg mice, and all progeny expressing either individual, neither, or both (Survivin/HGF) transgenes were UV-treated as neonates and then monitored for 43 weeks. Melanocytes in neonatal Survivin+/HGF+ mouse skin were less susceptible to UV-induced apoptosis than those from Survivin−/HGF+ mice. Onset of melanocytic tumors was earlier (median, 18 versus 24 weeks; P = 0.01, log-rank test), and overall tumor density was greater (7.7 versus 5.2 tumors per mouse; P = 0.04) in Survivin+/HGF+ compared with Survivin−/HGF+ mice. Strikingly, melanomas arising in Survivin+/HGF+ mice showed a greater tendency for lymph node (35% versus 0%; P = 0.04) and lung (53% versus 22%) metastasis and lower rates of spontaneous apoptosis than those in Survivin−/HGF+ mice. These studies show a role for Survivin in promoting both early and late events of UV-induced melanoma development in vivo. [Cancer Res 2007;67(11):5172–8]