Evaluating requests for physician-assisted suicide. A survey among German oncologists.

BACKGROUND: Cancer patients form a notable proportion of requestors for physician-assisted suicide (PAS). This manuscript provides data on German oncologists' views concerning due criteria for the assessment of requests for PAS and quality assurance. METHODS: The German Society of Haematology and Medical Oncology (DGHO) has conducted a survey among its members to elicit data about practices and views on regulating PAS in March 2021. Descriptive analysis and bivariate logistic regression of quantitative data on socio-demographic and other determinants possibly associated with respondents' views on PAS as well as content analysis of qualitative data were performed. RESULTS: About 57.1% (n = 425) of respondents (n = 745) indicated that they had been asked for information about PAS by patients. Information about palliative (92.7%; n = 651) and psychological care options (85.6%; n = 598) was deemed most important in cases of requests for PAS. More than half of the respondents (57.6%; n = 429) were in favour of a formal expert assessment of decisional capacity and about 33.4% (n = 249) favoured a time span of 14 days between the counselling and prescription of a lethal drug. There was no association between participants who received more requests and a preference for disclosing publicly their willingness to assist with suicide. A majority of respondents requested measures of quality assurance (71.3%; n = 531). CONCLUSION: According to respondents' views, the regulation of PAS will require diligent procedures regarding the assessment of decisional capacity and counselling. The findings suggest that the development of adequate and feasible criteria to assess the quality of practices is an important task.

Larynx proteomics after jellyfish collagen IL: Increased ECM/collagen and suppressed inflammation.

Objectives/Hypothesis: Compare proteomic profiles of rabbit vocal folds (VFs) injected with micronized cross-linked jellyfish collagen "collagen Type 0" (MX-JC) against two clinical products for injection medialization laryngoplasty (IL). Study Design: Animal model. Methods: Left recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits (N = 6/group). Group 1 received (MX-JC) and adipose-derived stem cells (ADSCs), Group 2, MX-JC alone; Group 3, cross-linked hyaluronic acid; and Group 4, micronized acellular dermis. Animals were sacrificed at 4 and 12 weeks. Proteomic profiling of injected versus noninjected VFs by nano-liquid chromatography, tandem mass spectrometry, and reactome gene ontology analysis was performed. Results: Overall, 37-61 proteins were found to be upregulated and 60-284 downregulated in injected versus non-injected VFs (>1.5 fold, false discovery rate-adjusted p < .05). Over-representation analysis (% of total) revealed top up-regulated pathways at 4 and 12 weeks, respectively: Group 1, keratan sulfate metabolism (46%) and cellular processes (29%); Group 2, extracellular matrix (ECM)/collagen processes (33%) and beta oxidation (39%); Group 3, cellular processes (50%) and energy metabolism (100%); and Group 4, keratan sulfate metabolism (31%) and inflammation (50%). Top downregulated pathways were: Group 1, Inflammation (36%) and glucose/citric acid metabolism (42%); Group 2, cell signaling (38%) and glucose/citric acid metabolism (35%); Group 3, keratan sulfate metabolism (31%) and ECM/collagen processes (48%); and Group 4, glucose/citric acid metabolism (33%) and ECM/collagen processes (43%). Conclusions: MX-JC "collagen Type 0" upregulates pathways related to ECM/collagen formation and downregulates pathways related to inflammation suggesting that it is promising biomaterial for IL. Level of Evidence: NA.

MRI imaging versus histologic volumetric estimation of residual injection laryngoplasty material.

Objectives: To examine the degree of agreement between MRI and histologically generated volumetric measurements of residual injection laryngoplasty material. Methods: Following left recurrent laryngeal nerve transection, rabbit vocal cords were injected with jellyfish collagen, Cymetra®, or Restylane®. Laryngeal tissue was harvested 4 or 12 weeks post injection followed by MRI imaging and histologic cross-sectioning. Two raters estimated the volume of remaining injection material in specimens within MRI and histologic axial cross sections. Wilcoxon signed rank tests were employed to detect gross differences between inter-rater measurements and between imaging modalities across time. Agreement between rater measurements and imaging (histology and MRI) was assessed using intra-class correlation coefficients. Results: Data was available from 16 rabbits sacrificed at 4 weeks (n = 8) and 12 weeks (n = 8). Inter-rater testing of MRI imaging revealed no significant differences (p > .05) between rater measurements across time points, and excellent agreement (0.93; 95% confidence interval 0.80-0.98) while histologically estimated volumes demonstrated a significant difference at 4 weeks (p < .05) and overall good agreement (0.89; 95% confidence interval 0.59-0.97). Comparison of MRI and histologically estimated volume measurements revealed significant differences at the 4-week time point (p < .05) but not at 12 weeks (p > .05). Overall, there is only moderate agreement between MRI and histology estimates (0.72; 95% confidence interval 0.22-0.90). Conclusions: MRI imaging demonstrates good reliability and similar estimates of volume to histologically estimated measurements of residual injection laryngoplasty material at time points clinically relevant for future injection laryngoplasty experiments. Level of Evidence: NA.

MRI Study of Jellyfish Collagen, Hyaluronic Acid, and Cadaveric Dermis for Injection Laryngoplasty.

OBJECTIVES/HYPOTHESIS: Test a new jellyfish collagen biomaterial aimed to increase duration of injection medialization laryngoplasty (IL) against two products in clinical practice. STUDY DESIGN: Animal model. METHODS: Left recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits (N = 6/group). Group 1 received micronized cross-linked jellyfish collagen (MX-JC) and adipose derived stem cells (ADSCs), Group 2, MX-JC alone, Group 3, cross-linked hyaluronic acid (X-HA), and Group 4, micronized acellular dermis (MACD). Animals were sacrificed at 4 and 12 weeks. Major outcomes were MRI tissue volumes and histopathology. RESULTS: After 100 µL IL MRI volumes (means ± STD) at 4 and 12 weeks were: Group 1: 27.2 ± 15.6 and 13.1 ± 5.2 µL, Group 2: 60.8 ± 18 and 27.8 ± 2.47 µL, Group 3: 27.4 ± 12 and 10.6 ± 8 µL, and Group 4: 37.5 ± 11 and 9.85 ± 1 µL. Group 2 volumes were largest and Group 3 were smallest in all comparisons (P < .05). Histologically, low grade inflammatory responses were observed in Group 1, mild histiocytic infiltration in Group 2, widespread muscle fiber loss in Group 3, and plasmocytic infiltration in Group 4. CONCLUSIONS: MX-JC showed the least resorption at 4 and 12 weeks among all groups. T cell inflammatory responses were observed with MX-JC but were reduced by 12 weeks while B cell immune responses, indicative of antibody priming, were predominantly noted with MACD. MX-JC + ADSC showed low grade immunity while the XHA showed greater myocyte loss compared to the other groups. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2452-E2460, 2021.

Impact of cochlear modiolus dose on hearing preservation following stereotactic radiosurgery for non-vestibular schwannoma neoplasms of the lateral skull base: a cohort study.

OBJECTIVE: Radiation dose to the cochlea has been proposed as a key prognostic factor in hearing preservation following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). However, understanding of the predictive value of cochlear dose on hearing outcomes following SRS for patients with non-VS tumors of the lateral skull base (LSB) is incomplete. The authors investigated rates of hearing loss following high-dose SRS in patients with LSB non-VS lesions compared with patients with VS. METHODS: Patients with LSB meningioma or jugular paraganglioma and serviceable pretreatment hearing who underwent SRS treatment during 2007-2016 and received a modiolus dose > 5 Gy were included in a retrospective cohort study, along with a similarly identified control group of consecutive patients with sporadic VS. RESULTS: Sixteen patients with non-VS tumors and a control group of 43 patients with VS met study criteria. Serviceable hearing, defined as American Academy of Otololaryngology-Head and Neck Surgery class A/B, was maintained in 13 non-VS versus 23 VS patients (81% vs 56%, p = 0.07). All 3 instances of hearing loss in non-VS patients were observed in cerebellopontine angle (CPA) meningiomas. Non-VS with preserved hearing had a median modiolus dose of 6.9 Gy (range 5.7-19.2 Gy), versus 7.4 Gy (range 5.4-7.6 Gy) in those patients with post-SRS hearing loss (p = 0.53). Sporadic VS patients received an overall median modiolus point-dose of 6.8 Gy (range 5.4-11.7 Gy). CONCLUSIONS: The modiolus dose threshold of 5 Gy does not predict hearing loss in patients with non-VS tumors undergoing SRS, suggesting that dosimetric parameters derived from VS may not be applicable to this population. Differential rates of hearing loss appear to vary by pathology, with paragangliomas and petroclival meningiomas demonstrating decreased risk of hearing loss compared to CPA meningiomas that may directly compress the cochlear nerve similarly to VS.

Highly Efficient One-Dimensional Triplet Exciton Transport in a Palladium-Porphyrin-Based Surface-Anchored Metal-Organic Framework.

Efficient photon-harvesting materials require easy-to-deposit materials exhibiting good absorption and excited-state transport properties. We demonstrate an organic thin-film material system, a palladium-porphyrin-based surface-anchored metal-organic framework (SURMOF) thin film that meets these requirements. Systematic investigations using transient absorption spectroscopy confirm that triplets are very mobile within single crystalline domains; a detailed analysis reveals a triplet transfer rate on the order of 1010 s-1. The crystalline nature of the SURMOFs also allows a thorough theoretical analysis using the density functional theory. The theoretical results reveal that the intermolecular exciton transfer can be described by a Dexter electron exchange mechanism that is considerably enhanced by virtual charge-transfer exciton intermediates. On the basis of the photophysical results, we predict exciton diffusion lengths on the order of several micrometers in perfectly ordered, single-crystalline SURMOFs. In the presently available samples, strong interactions of excitons with domain boundaries present in these metal-organic thin films limit the diffusion length to the diameter of these two-dimensional grains, which amount to about 100 nm. Our results demonstrate high potential of SURMOFs for light-harvesting applications.

Reaction of porphyrin-based surface-anchored metal-organic frameworks caused by prolonged illumination.

Crystalline surface-anchored metal-organic framework (SURMOF) thin films made from porphyrin-based organic linkers have recently been used in both photon upconversion and photovoltaic applications. While these studies showed promising results, the question of photostability in this organic-inorganic hybrid material has to be investigated before applications can be considered. Here, we combine steady-state photoluminescence, transient absorption, and time-resolved electron paramagnetic resonance spectroscopy to examine the effects of prolonged illumination on a palladium-porphyrin based SURMOF thin film. We find that phototreatment leads to a change in the material's photoresponse caused by the creation of stable products of photodecomposition - likely chlorin - inside the SURMOF structure. When the mobile triplet excitons encounter such a defect site, a short-lived (80 ns) cation-anion radical pair can be formed by electron transfer, wherein the charges are localized at a porphyrin and the photoproduct site, respectively.

Time-course mass spectrometry data of adipose mesenchymal stem cells acquiring chondrogenic phenotype.

OBJECTIVES: Rabbit adipose mesenchymal stem cells were used for the purpose of studying acquisition of the chondrogenic phenotype over time at 1, 14 and 28 days after in vitro incubation with differentiation media, using nano-liquid chromatography electrospray ionization tandem mass spectrometry analysis. This was part of a preliminary study of the behavior of differentiated adipose stem cells for use in a rabbit model of laryngoplasty. DATA DESCRIPTION: The data comprise .MGF, .RAW, .MZID, and .XLSX, lists of peaks, peptides and proteins identified by nano-flow liquid chromatography electrospray ionization tandem mass spectrometry analysis upon incubation with non-differentiating (ND) or chondrogenic differentiating (CHD) media (ProteomeXchange ID PXD010236). XLSX files contain the following information: day 1 CT (control, N = 3499 proteins), day 14 ND (N = 3106 proteins), day 28 ND (N = 3116 proteins), day 14 CHD (N = 2901 proteins), and day 28 CHD (N = 2876 proteins). Proteins are characterized with respect to their - 10lgP value, percent coverage, number of total as well as unique peptides after trypsin digestion, derivatization method (carbamidomethylation, oxidation, or combined carbamidomethylation + oxidation), average mass, and include a full description.

Histone Variants as Stem Cell Biomarkers for Long-Term Injection Medialization Laryngoplasty.

OBJECTIVES/HYPOTHESIS: Vocal fold (VF) paralysis by sectioning the recurrent laryngeal nerve dramatically impacts the life of thyroidectomy patients. Volume-expanding materials can temporarily restore VF medialization. To prolong this benefit, adipose mesenchymal stem cells (ADSCs) and micronized acellular dermis (MACD) were co-injected in a rabbit model of injection medialization laryngoplasty. Biomarkers of in situ proliferation were identified by mass spectrometry proteomics and pathway analysis to guide future efforts to increase the length of benefit. METHODS: ADSCs were expanded and/or differentiated into chondrocytes (CHON) as collagen microspheres. After VF paralysis rabbits received MACD, MACD + undifferentiated ADSC, or MACD+CHON, ADSCs differentiated into chondrocytes. After 12 weeks, animals were sacrificed and 5-µm paraffin-embedded cryosections were prepared from larynges for hematoxylin and eosin visualization and nanoflow liquid chromatography electrospray-ionization tandem-mass spectrometry analysis of tissue collections. Validated proteins were processed by Venn subtraction and gene ontology (GO) overrepresentation analysis to identify unique pathways and biomarkers. RESULTS: Confirmed proteins numbered 147 (MACD), 1,243 (MACD+ADSC), and 1,033 (MACD+CHON). Totally, 333 proteins were uniquely found in the MACD+ADSC group, including mesenchymal surface markers CD9, CD44, fibronectin, and vimentin. Over 70% of proteins belonged to catalytic activity and binding GO categories, with the histone (H) family being overrepresented (P < 0.05). Histone variants H3.3, H2A.V, and H2A.Z (associated with open chromatin states) were overrepresented in the MACD+ADSC group, whereas structural histones H2A, H2B, and H4 were not. CONCLUSION: Biomarkers, including atypical histones, are associated with in vivo proliferation of ADSCs and an expanded VF medialization volume. LEVEL OF EVIDENCE: NA Laryngoscope, 128:E402-E408, 2018.

The Janus-faced chromophore: a donor-acceptor dyad with dual performance in photon up-conversion.

An electron donor-acceptor dyad based on BODIPY (acceptor) and anthracene (donor) plays either the role of sensitizer or emitter in triplet-triplet annihilation photon up-conversion (TTA-UC). This Janus-like behavior was achieved via altering the relative ordering of charge-transfer and local excited state energies in the dyad through the polarity of TTA-UC media.

Preliminary results of tissue-engineered injection laryngoplasty material in a rabbit model.

OBJECTIVES/HYPOTHESIS: Design and test a novel biomaterial for injection laryngoplasty aimed to increase the duration of effectiveness of micronized acellular dermis. STUDY DESIGN: Animal model. METHODS: Injection laryngoplasty was performed in three groups (n = 5) of New Zealand White rabbits. Acellular dermis was either used alone as a control (group 1), was combined with undifferentiated stem cells (group 2), or with predifferentiated chondrocytic cells (group 3). Groups 2 and 3 were supplemented with growth factors. Animals were sacrificed 4 and 12 weeks after laryngoplasty and histologic analysis was completed. The major outcome measure was volume of tissue remaining. RESULTS: After 4 weeks, the mean volume of tissue remaining was 341 ± 89 mm3 , 295 ± 102 mm3 , and 133 ± 15 mm3 , for groups 1 to 3, respectively. At the 12-week time point, volumes were 62 ± 62 mm3 , 235 ± 35 mm3 , and 107 ± 99 mm3 . After 12 weeks, there was a significantly higher volume in group 2 compared to group 1 or 3 (P = .01, P = .04). Volumes between week 4 and week 12 were significantly lower in group 1 (P = .02), but not significantly different for groups 2 and 3 (P = .38, P = .74). Histologic evaluation revealed a robust lymphocytic infiltration in all cases as well as morphologic and immunophenotypic features suggestive of chondrogenic differentiation in a single animal. CONCLUSIONS: Micronized acellular dermis combined with stem cells and growth factors showed significantly less resorption 12 weeks after injection laryngoplasty compared to micronized acellular dermis alone. Groups using novel tissue-engineered biomaterial showed a lower resorption rate over time compared with acellular dermis alone. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:160-167, 2018.

The Utility of Sentinel Node Biopsy for Sinonasal Melanoma.

Objective Report two positive sentinel node biopsies for sinonasal melanoma. Design Retrospective review. Setting Academic tertiary care center. Participants Patients who underwent sentinel node biopsy for sinonasal melanoma between November 1, 2014 and November 1, 2015. Main Outcome Measures Clinical course. Results Two patients were identified. Patient 1 (83M) presented with a sinonasal melanoma anterior to the left inferior turbinate and was clinically N0 neck. Lymphoscintigraphy revealed two sentinel nodes in the ipsilateral and three in the contralateral cervical basins. The left level I sentinel node was positive for melanoma and lymphadenectomy showed no additional metastases. Patient 2 (71F) presented after incomplete resection of a sinonasal melanoma of the left posterior maxillary sinus wall and was clinically N0 neck. Lymphoscintigraphy with single-photon emission computed tomography (SPECT/CT) localization revealed one sentinel node in the parapharyngeal space and another in the ipsilateral cervical basin. Metastatic melanoma was found in both nodes and completion lymphadenectomy was negative for additional disease. Both patients developed distant metastasis in less than 1 year after surgical resection but responded well to adjuvant immunomodulatory chemotherapeutic agents. Conclusion Sentinel node biopsy for sinonasal melanoma can provide crucial clinical evidence of regional metastasis prior to overt clinical signs and symptoms. This intraoperative tool has the potential to improve detection of regional metastasis and improve long-term outcomes of this aggressive malignancy.

[Priorities of German Oncologists. Results of the "choosing wisely" survey of the German Society of Hematology and Medical Oncology (DGHO)]. / Prioritäten deutscher Onkologen. Auswertung der "Klug entscheiden"-Umfrage der Deutschen Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO).

Background During the preparation of "choosing wisely" recommendations, the German Society of Hematology and Medical Oncology (DGHO) had performed a member survey. The large body of replies was systematically and quantitatively analyzed for this report. Methods Replies to the draft recommendations are quantified. Free text replies were iteratively categorized in three levels according to medical categories and additionally, according to their general target of necessary action. Results 492 members completed the survey within the given limit of 2 weeks. Draft recommendations against oversupply were widely supported (77 %-88 %). 1598 free text replies were analyzed. Unnecessary use of resources was requested in several fields in accordance with our recommendations. Strong demand was put forward regarding soft factors: "talking medicine", individually tailored therapy, supportive medicine and palliative care (51 % together) and social resources (11 %). Possible under-supply was less frequently described in fields of expensive measures (17 % of replies). Conclusion In the replies to our survey, we found a strong statement for a plus in talking medicine in oncology. Every physician caring for these patients can contribute to this demand. Structural improvements in continuing education and reimbursement in this field are desirable.

Histologic Evaluation of Micronized AlloDerm After Injection Laryngoplasty in a Rabbit Model.

OBJECTIVES/HYPOTHESIS: Micronized AlloDerm is a commonly used injectable material for injection laryngoplasty; however, the histologic response to laryngeal implantation and resorption rate over time have not been elucidated. This study aimed to evaluate the in vivo response of micronized AlloDerm over time after laryngeal implantation using a rabbit model. STUDY DESIGN: Animal model. METHODS: The left recurrent laryngeal nerve was sectioned in five New Zealand White rabbits to create a vocal cord paralysis. Two weeks later, injection laryngoplasty was performed with 100 µL of micronized AlloDerm. Animals were sacrificed 4 (two rabbits) and 12 (three rabbits) weeks after injection. Histologic sections were stained and evaluated by a single pathologist. Volume estimates were made by assuming the implant took an ellipsoid shape using dimensions calculated from histologic slides. RESULTS: In all cases, histological analysis revealed a lymphocytic inflammatory response infiltrating the peripheral margins of injection. After 4 weeks, the volume of injected material remaining in two rabbits was 404 and 278 mm3 (average 341 mm3 ). After 12 weeks, the volume of injected material remaining in three rabbits was 0, 61, and 124 mm3 (average 62 mm3 ), an 82% difference in volume of material between animals sacrificed at 4 weeks versus 12 weeks. CONCLUSIONS: Injection laryngoplasty using micronized AlloDerm induces a lymphocytic inflammatory response after injection in a rabbit model. Though a significant amount of material remains after 4 weeks, by 12 weeks the majority has been reabsorbed. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E166-E169, 2017.

Photon Upconversion at Crystalline Organic-Organic Heterojunctions.

Triplet transfer across a surface-anchored metal-organic-framework heterojunction is demonstrated by the observation of triplet-triplet annihilation photon -upconversion in a sensitizer-emitter heterostructure. Upconversion thresholds under 1 mW cm-2 are achieved. In the broader context, the double-electron-exchange mechanism of triplet transfer indicates that the heterojunction quality is sufficient for electrons to move between layers in this solution-processed crystalline heterostructure.

A unique case of penetrating neck and cervical spine trauma resulting in vertebral artery transection and internal carotid artery laceration.

OBJECTIVES: Describe the presentation and treatment of a patient who suffered a penetrating cervical trauma resulting in occlusion of the vertebral and internal carotid arteries. METHODS: The electronic medical record was used to collect information pertaining to the patient's clinical history. RESULTS: A 20-year-old male suffered a unique penetrating neck injury resulting in simultaneous injuries to the internal carotid and vertebral arteries as demonstrated by pre-operative angiography. Combined endovascular and open surgical approaches were utilized to successfully manage the vascular injuries prior to foreign body extraction. CONCLUSION: Complex penetrating cervical trauma is best managed with a multidisciplinary and multimodality approach. In appropriately selected patients, pre-operative angiography is a critical diagnostic modality that can prevent life-threatening hemorrhage following foreign body extraction.

Management of Geniculate Ganglion Hemangiomas: Case Series and Systematic Review of the Literature.

OBJECTIVE: To analyze facial nerve (FN) outcomes based on duration of FN palsy and surgical strategy in patients with geniculate ganglion hemangiomas (GGH). STUDY DESIGN: Case series and systematic review of the literature. SETTING: Tertiary care center. SUBJECTS AND METHODS: All patients undergoing surgical resection of GGH from 1992 to 2014 were studied and a review of the English literature was performed. RESULTS: One hundred twenty unique patients (mean age 41.4 yrs, 44% female) were identified with GGH: 8 in the current series and 112 from the literature review. Of these patients, 94% presented with FN weakness, 18% reported hemifacial spasm, and 16% had hearing loss at presentation. Eleven patients underwent an initial period of observation, 6 of which experienced either growth or progression of FN dysfunction. One hundred fourteen subjects ultimately underwent surgical intervention. The average preoperative House-Brackmann (HB) score was 4.6 and the mean duration of preoperative FN palsy was 27 months (range, 1-132). The average postoperative HB score was 3.5 at the last follow-up. Anatomical FN preservation was reported in 44% of patients. Duration of FN palsy ≤12 months was associated with better pre- and postoperative FN outcome (HB 4.1 vs 5.1, p = 0.01 and 2.9 vs 4.0, p < 0.001, respectively). FN preservation was also associated with better postoperative FN outcome compared with interposition grafting (HB 2.6 vs 3.9, p < 0.001). CONCLUSION: GGHs are rare benign vascular malformations that present with progressive FN palsy. In most patients, early surgical intervention should be considered since shorter duration of FN paralysis and anatomical preservation of the FN are significant predictors of final FN outcome.

Myhre-LAPs syndrome and intubation related airway stenosis: keys to diagnosis and critical therapeutic interventions.

OBJECTIVES: Myhre-LAPS syndrome is a recently recognized disease caused by a mutation in the SMAD4 gene. This results in a range of pathology including laryngotracheal stenosis, arthropathy, prognathism and short stature, or LAPS syndrome. We aim to delineate the role of intubation in development of airway stenosis in these patients as well as provide insight into diagnosis and management of this syndrome. Herein we present four patients with Myhre-LAPS syndrome complicated by airway stenosis and perform a systematic review of all cases of Myhre-LAPS syndrome with reported airway pathology. STUDY DESIGN: Retrospective review METHODS: All patients diagnosed with Myhre-LAPS syndrome and airway stenosis at a single institution from 1981 to 2014 were reviewed. RESULTS: Four patients (4F, median age 42) were identified that met inclusion criteria. Initial presenting signs included progressive shortness of breath, dyspnea on exertion and respiratory distress. All four (100%) patients had multi-level airway stenosis most commonly in the subglottic and glottic regions and all patients had undergone at least one endotracheal intubation prior to presentation. One patient with a history of nasal tracheal intubation presented with nasal obstruction and was found to have choanal as well as subglottic stenosis. Two of the four (50%) patients are tracheostomy tube dependent, 1/4 (25%) died of a fatal cardiac arrhythmia and 1/4 (25%) has had 6 endoscopic treatments for subglottic stenosis in 4 years with rapid symptom recurrence. CONCLUSIONS: Myhre-LAPS syndrome is characterized by progressive systemic fibrosis and patients are diagnosed by characteristic findings of prognathism, short stature, abnormal facies, and thick skin among other abnormalities. Airway management is complicated by recurrent, refractory subglottic stenosis often preceded by elective intubation as well as maxillary hypoplasia, trismus, and limited neck extension. Endotracheal intubation and surgical intervention should be approached with caution in these patients and multidisciplinary care teams are necessary to address all manifestations of this syndrome.

Cavernous hemangiomas of the internal auditory canal and cerebellopontine angle.

OBJECTIVE: To review the clinical presentation, differential diagnosis, management strategy, and outcomes after microsurgical resection of cavernous hemangiomas (CHs) arising primarily within the internal auditory canal (IAC) and cerebellopontine angle (CPA). PATIENTS: Twelve patients (10 men; aged 18-66 yr) were included from 1982 to 2012 from one of two tertiary academic referral centers. INTERVENTION(S): All patients underwent preoperative imaging evaluation and subsequent microsurgical resection. MAIN OUTCOME MEASURE(S): American Academy of Otolaryngology-Head and Neck Surgery hearing class, facial nerve function, and tumor control. RESULTS: The most common presenting symptoms were ipsilateral sensorineural hearing loss, nonpulsatile tinnitus, and vertigo. Three presented with facial paresis, 10 had lost serviceable hearing preoperatively. All lesions demonstrated heterogeneous enhancement with gadolinium and hyperintense signal on T2-weighted imaging. The median tumor diameter was 8 mm; eight CHs were confined to the IAC, whereas four involved the CPA. Tumors were accessed via a translabyrinthine approach in eight cases, retrosigmoid craniotomy in three cases, and a middle cranial fossa approach in one case. Ten patients received gross total resection, whereas two underwent subtotal removal. Neither patient with serviceable preoperative hearing retained useful hearing after resection. Eight of the nine patients with normal preoperative facial nerve function retained House-Brackmann grade 1 function after surgery. One patient had residual tumor treated with postoperative stereotactic radiosurgery. CONCLUSIONS: Primary CHs of the IAC and CPA are rare and present clinically and radiographically similar to vestibular schwannoma. Microsurgical resection provides excellent facial nerve outcomes and tumor control for most patients; however, the majority of individuals will acquire non-serviceable hearing either from disease or as a result of treatment.

Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats.

We show that human embryonic stem cell-derived dopaminergic neurons survived transplantation to the neurotoxin 6-hydroxydopamine-lesioned rat striatum and, in combination with the cells newly differentiated from their progenitors, contributed to locomotive function recovery at 5 months. The animal behavioral improvement was correlated with the dopamine neurons present in the graft. Although the donor cells contained forebrain and midbrain dopamine neurons, the dopamine neurons present in the graft mainly exhibited a midbrain, or nigra, phenotype, suggesting the importance of midbrain dopamine neurons in functional repair. Furthermore, progenies of grafted cells were neurons and glia with greatly diminished mitotic activity by 5 months. Thus, the in vitro-produced human dopamine neurons can functionally engraft in the brain.