Crown-of-thorns starfish spines secrete defence proteins.

Background: The crown-of-thorns starfish (COTS; Acanthaster species) is a slow-moving corallivore protected by an extensive array of long, sharp toxic spines. Envenomation can result in nausea, numbness, vomiting, joint aches and sometimes paralysis. Small molecule saponins and the plancitoxin proteins have been implicated in COTS toxicity. Methods: Brine shrimp lethality assays were used to confirm the secretion of spine toxin biomolecules. Histological analysis, followed by spine-derived proteomics helped to explain the source and identity of proteins, while quantitative RNA-sequencing and phylogeny confirmed target gene expression and relative conservation, respectively. Results: We demonstrate the lethality of COTS spine secreted biomolecules on brine shrimp, including significant toxicity using aboral spine semi-purifications of >10 kDa (p > 0.05, 9.82 µg/ml), supporting the presence of secreted proteins as toxins. Ultrastructure observations of the COTS aboral spine showed the presence of pores that could facilitate the distribution of secreted proteins. Subsequent purification and mass spectrometry analysis of spine-derived proteins identified numerous secretory proteins, including plancitoxins, as well as those with relatively high gene expression in spines, including phospholipase A2, protease inhibitor 16-like protein, ependymin-related proteins and those uncharacterized. Some secretory proteins (e.g., vitellogenin and deleted in malignant brain tumor protein 1) were not highly expressed in spine tissue, yet the spine may serve as a storage or release site. This study contributes to our understanding of the COTS through functional, ultrastructural and proteomic analysis of aboral spines.

ART714 is a best-in-class antileukemic 2-carbon-linked dimeric artemisinin derivative.

PURPOSE: It has become increasingly clear that new multiagent combination regimens are required to improve survival rates in acute myeloid leukemia (AML). We recently reported that ART631, a first-in-class 2-carbon-linked artemisinin-derived dimer (2C-ART), was not only efficacious as a component of a novel three-drug combination regimen to treat AML, but, like other synthetic artemisinin derivatives, demonstrated low clinical toxicity. However, we ultimately found ART631 to have suboptimal solubility and stability properties, thus limiting its potential for clinical development. METHODS: We assessed 22 additional 2C-ARTs with documented in vivo antimalarial activity for antileukemic efficacy and physicochemical properties. Our strategy involved culling out 2C-ARTs inferior to ART631 with respect to potency, stability, and solubility in vitro, and then validating in vivo pharmacokinetics, pharmacodynamics, and efficacy of one 2C-ART lead compound. RESULTS: Of the 22 2C-ARTs, ART714 was found to have the most optimal in vitro solubility, stability, and antileukemic efficacy, both alone and in combination with the BCL2 inhibitor venetoclax (VEN) and the kinase inhibitor sorafenib (SOR). ART714 was also highly effective in combination with VEN and the FMS-like tyrosine kinase 3 inhibitor gilteritinib (GILT) against MOLM14 AML xenografts. CONCLUSION: We identified ART714 as our best-in-class antileukemic 2C-ART, based on in vitro potency and pharmacologic properties. We established its in vivo pharmacokinetics and demonstrated its in vitro cooperativity with VEN and SOR and in vivo activities of combinations of ART714, VEN, and GILT. Additional research is indicated to define the optimal niche for the use of ART714 in treatment of AML.

Laterality of previous stoke affects endovascular thrombectomy outcomes.

BACKGROUND: Investigations into the effect of previous stroke on thrombectomy outcomes have yielded conflicting results, and are limited by small sample sizes. We present the results of a large single center retrospective study aimed at investigating the effect of chronic stroke laterality on thrombectomy outcomes. METHODS: A prospectively maintained database was queried for all thrombectomy cases conducted between December 2014 and January 2020, and patient imaging was prospectively reviewed for evidence of prior supratentorial infarction. Procedural, clinical, and demographic characteristics were recorded, and good clinical outcome was defined as a 90 day modified Rankin Scale (mRS) score of <2 or mRS score unchanged if baseline was >2. RESULTS: The final analysis cohort included 555 patients, 79 of whom were found to have radiographic evidence of prior chronic infarcts. On univariate analysis, patients with any chronic supratentorial infarct achieved a lower rate of good clinical outcome than patients with no chronic infarct (22.8% vs 41.0%, p=0.0021). With regard to subgroups, this difference remained only in patients with ipsilateral (14.3%, p=0.0018) and bilateral (11.8%, p=0.015) lesions. Patients with chronic contralateral supratentorial infarcts were no less likely to achieve good outcomes (40.7%, p=0.98). After multivariate regression controlling for age, sex, and baseline mRS, chronic ipsilateral infarcts (OR 0.22, CI 0.07 to 0.67) and chronic bilateral infarcts (OR 0.19, CI 0.04 to 0.85) were the only independent predictors of poor outcome in endovascular thrombectomy patients. CONCLUSIONS: In this single center retrospective study of thrombectomy patients with chronic supratentorial infarcts, the laterality of the previous stroke significantly affected the likelihood of good clinical outcomes.

Mitochondrial Dysfunction Is a Driver of SP-2509 Drug Resistance in Ewing Sarcoma.

Expression of the fusion oncoprotein EWS/FLI causes Ewing sarcoma, an aggressive pediatric tumor characterized by widespread epigenetic deregulation. These epigenetic changes are targeted by novel lysine-specific demethylase-1 (LSD1) inhibitors, which are currently in early-phase clinical trials. Single-agent-targeted therapy often induces resistance, and successful clinical development requires knowledge of resistance mechanisms, enabling the design of effective combination strategies. Here, we used a genome-scale CRISPR-Cas9 loss-of-function screen to identify genes whose knockout (KO) conferred resistance to the LSD1 inhibitor SP-2509 in Ewing sarcoma cell lines. Multiple genes required for mitochondrial electron transport chain (ETC) complexes III and IV function were hits in our screen. We validated this finding using genetic and chemical approaches, including CRISPR KO, ETC inhibitors, and mitochondrial depletion. Further global transcriptional profiling revealed that altered complex III/IV function disrupted the oncogenic program mediated by EWS/FLI and LSD1 and blunted the transcriptomic response to SP-2509. IMPLICATIONS: These findings demonstrate that mitochondrial dysfunction modulates SP-2509 efficacy and suggest that new therapeutic strategies combining LSD1 with agents that prevent mitochondrial dysfunction may benefit patients with this aggressive malignancy.

Comparative study of intracranial access in thrombectomy using next generation 0.088 inch guide catheter technology.

BACKGROUND: Most conventional 0.088 inch guide catheters cannot safely navigate intracranial vasculature. The objective of this study is to evaluate the safety of stroke thrombectomy using a novel 0.088 inch guide catheter designed for intracranial navigation. METHODS: This is a multicenter retrospective study, which included patients over 18 years old who underwent thrombectomy for anterior circulation large vessel occlusions. Technical outcomes for patients treated using the TracStar Large Distal Platform (TracStar LDP) or earlier generation TRX LDP were compared with a matched cohort of patients treated with other commonly used guide catheters. The primary outcome measure was device-related complications. Secondary outcome measures included guide catheter failure and time between groin puncture and clot engagement. RESULTS: Each study arm included 45 patients. The TracStar group was non-inferior to the control group with regard to device-related complications (6.8% vs 8.9%), and the average time to clot engagement was 8.89 min shorter (14.29 vs 23.18 min; p=0.0017). There were no statistically significant differences with regard to other technical outcomes, including time to recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2B). The TracStar was successfully advanced into the intracranial internal carotid artery in 33 cases (73.33%); in three cases (6.67%), it was swapped for an alternate catheter. Successful reperfusion (mTICI 2B-3) was achieved in 95.56% of cases. Ninety-day follow-up data were available for 86.67% of patients, among whom 46.15% had an modified Rankin Score of 0-2%, and 10.26% were deceased. CONCLUSIONS: Tracstar LDP is safe for use during stroke thrombectomy and was associated with decreased time to clot engagement. Intracranial access was regularly achieved.

Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax.

Artemisinins are active against human leukemia cell lines and have low clinical toxicity in worldwide use as antimalarials. Because multiagent combination regimens are necessary to cure fully evolved leukemias, we sought to leverage our previous finding that artemisinin analogs synergize with kinase inhibitors, including sorafenib (SOR), by identifying additional synergistic antileukemic drugs with low toxicity. Screening of a targeted antineoplastic drug library revealed that B-cell lymphoma 2 (BCL2) inhibitors synergize with artemisinins, and validation assays confirmed that the selective BCL2 inhibitor, venetoclax (VEN), synergized with artemisinin analogs to inhibit growth and induce apoptotic cell death of multiple acute leukemia cell lines in vitro. An oral 3-drug "SAV" regimen (SOR plus the potent artemisinin-derived trioxane diphenylphosphate 838 dimeric analog [ART838] plus VEN) killed leukemia cell lines and primary cells in vitro. Leukemia cells cultured in ART838 had decreased induced myeloid leukemia cell differentiation protein (MCL1) levels and increased levels of DNA damage-inducible transcript 3 (DDIT3; GADD153) messenger RNA and its encoded CCATT/enhancer-binding protein homologous protein (CHOP), a key component of the integrated stress response. Thus, synergy of the SAV combination may involve combined targeting of MCL1 and BCL2 via discrete, tolerable mechanisms, and cellular levels of MCL1 and DDIT3/CHOP may serve as biomarkers for action of artemisinins and SAV. Finally, SAV treatment was tolerable and resulted in deep responses with extended survival in 2 acute myeloid leukemia (AML) cell line xenograft models, both harboring a mixed lineage leukemia gene rearrangement and an FMS-like receptor tyrosine kinase-3 internal tandem duplication, and inhibited growth in 2 AML primagraft models.

Venetoclax and pegcrisantaspase for complex karyotype acute myeloid leukemia.

Complex karyotype acute myeloid leukemia (CK-AML) has a dismal outcome with current treatments, underscoring the need for new therapies. Here, we report synergistic anti-leukemic activity of the BCL-2 inhibitor venetoclax (Ven) and the asparaginase formulation Pegylated Crisantaspase (PegC) in CK-AML in vitro and in vivo. Ven-PegC combination inhibited growth of multiple AML cell lines and patient-derived primary CK-AML cells in vitro. In vivo, Ven-PegC showed potent reduction of leukemia burden and improved survival, compared with each agent alone, in a primary patient-derived CK-AML xenograft. Superiority of Ven-PegC, compared to single drugs, and, importantly, the clinically utilized Ven-azacitidine combination, was also demonstrated in vivo in CK-AML. We hypothesized that PegC-mediated plasma glutamine depletion inhibits 4EBP1 phosphorylation, decreases the expression of proteins such as MCL-1, whose translation is cap dependent, synergizing with the BCL-2 inhibitor Ven. Ven-PegC treatment decreased cellular MCL-1 protein levels in vitro by enhancing eIF4E-4EBP1 interaction on the cap-binding complex via glutamine depletion. In vivo, Ven-PegC treatment completely depleted plasma glutamine and asparagine and inhibited mRNA translation and cellular protein synthesis. Since this novel mechanistically-rationalized regimen combines two drugs already in use in acute leukemia treatment, we plan a clinical trial of the Ven-PegC combination in relapsed/refractory CK-AML.

A Novel 2-Carbon-Linked Dimeric Artemisinin With Potent Antileukemic Activity and Favorable Pharmacology.

Acute myeloid leukemia (AML) remains a devastating disease, with low cure rates despite intensive standard chemotherapy regimens. In the past decade, targeted antileukemic drugs have emerged from research efforts. Nevertheless, targeted therapies are often effective for only a subset of patients whose leukemias harbor a distinct mutational or gene expression profile and provide only transient antileukemic responses as monotherapies. We previously presented single agent and combination preclinical data for a novel 3-carbon-linked artemisinin-derived dimer (3C-ART), diphenylphosphate analog 838 (ART838), that indicates a promising approach to treat AML, given its demonstrated synergy with targeted antileukemic drugs and large therapeutic window. We now report new data from our initial evaluation of a structurally distinct class of 2-carbon-linked dimeric artemisinin-derived analogs (2C-ARTs) with prior documented in vivo antimalarial activity. These 2C-ARTs have antileukemic activity at low (nM) concentrations, have similar cooperativity with other antineoplastic drugs and comparable physicochemical properties to ART838, and provide a viable path to clinical development.

Republished: First clinical report of aspiration through a novel 0.088-inch catheter positioned in the M1 middle cerebral artery for ELVO thrombectomy.

Two patients, separated by 1 year, underwent mechanical thrombectomy using next generation, highly navigable 0.088-inch large bore catheters, which were navigated to and aspirated within the M1 middle cerebral artery segment. Case 1 demonstrates the first reported clinical application of this technique used in conjunction with stent retriever and direct aspiration through an intermediate catheter, resulting in modified thrombolysis in cerebral infarction (mTICI) score 3 recanalisation, and a 90-day modified Rankin Score of 1. In case 2, direct on-clot aspiration was applied through a 0.088-inch guide catheter in the left M1 segment, resulting in mTICI score 3 recanalisation and a National Institutes of Health Stroke Scale score of 1 at discharge. There was no evidence of untoward events in either case. Advancement of a 0.088-inch catheter into the M1 segment offers potential benefits to thrombectomy by improving device-thrombus interaction, inducing local flow arrest and protecting proximal vessels from embolus to new territories.

Langerhans Cell Histiocytosis of the Temporal Bone.

Background: Langerhans cell histiocytosis (LCH) of the temporal bone is an uncommon disease that primarily affects the pediatric population; fewer than 40 adult cases have been reported in the literature. We present a rare case of LCH of the temporal bone in an adult patient and describe its clinical presentation, histopathologic findings, and management. Case Report: A 21-year-old male presented to the emergency department with progressively worsening right-sided ear pain refractory to outpatient oral antibiotics. Physical examination revealed mastoid tenderness and decreased right-sided hearing. Computed tomography (CT) scan suggested coalescent mastoiditis; the patient responded to inpatient antibiotics and was discharged. He returned 9 days later with persistent symptoms. Repeat CT scan revealed an osteolytic lesion on the temporal bone, and the patient was indicated for surgery. Intraoperative histology was consistent with LCH. Subsequent surveillance magnetic resonance imaging (MRI) suggested persistence of disease, and the patient responded to a course of radiation. Three months following radiotherapy, surveillance MRI and positron emission tomography scans revealed no evidence of recurrent disease. Conclusion: Diagnosis of LCH of the temporal bone is frequently delayed because of misdiagnosis of more common otologic diseases, including otitis media, otitis externa, and mastoiditis. The clinician's index of suspicion for LCH should be high if imaging reveals an osteolytic defect of the temporal bone; confirmation is via immunohistostaining of biopsy samples. The majority of cases respond to surgery, radiation, chemotherapy, or combination therapy, but delays in diagnosis and treatment may increase morbidity. Increased physician awareness of LCH of the temporal bone, particularly among adults, may help to improve patient outcomes.

Complications Associated with Medical Tourism for Facial Rejuvenation: A Systematic Review.

BACKGROUND: Medical tourism for cosmetic surgery has become increasingly popular in recent years. The existing literature has identified poor outcomes associated with general cosmetic tourism; however, the complications associated with cosmetic tourism for facial rejuvenation remain poorly understood. The aims of this study are to delineate the risk profile associated with medical tourism for facial rejuvenation. METHODS: A systematic review of PubMed, MEDLINE, and Embase was performed through January 2019 using the PRISMA guidelines. Search terms included combinations of keywords including medical tourism and plastic surgery and other related nomenclature. Articles published in English relevant to medical tourism for facial rejuvenation and its associated complications were examined. RESULTS: We identified six retrospective studies including 31 patients who had obtained facial rejuvenation procedures abroad and experienced treatment-associated complications. Twenty-five of 26 listed patients (96%) were female (age range 33-62 years). Departure nations included the USA, Switzerland, England, Ireland, Australia, and Thailand. Destination nations included the Dominican Republic, Cyprus, the USA, Colombia, Thailand, India, and China. Procedures included blepharoplasty, facelift, rhinoplasty, chin lift, and injections with botulinum toxin and dermal fillers. Complications included abscess, poor cosmesis, facial nerve palsy, and death. CONCLUSIONS: We present the first study to systematically review the complications associated with medical tourism for facial rejuvenation. No definitive conclusions can be made given the paucity of relevant data, its clinical and statistical heterogeneity, and small sample size. Additional research is warranted to help inform patients who seek facial rejuvenation procedures abroad and to better understand the health system implications associated with cosmetic tourism for facial rejuvenation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Role of Steroids in Preventing Osteoradionecrosis of the Head and Neck: A Systematic Review.

OBJECTIVE: The aim of this study was to summarize the effectiveness of steroids in the prevention of osteoradionecrosis of the head and neck. DATA SOURCES: PubMED, MEDLINE, Embase, Google Scholar, and Cochrane trial registries. METHODS: A systematic review of these data sources was performed through September 2018 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included were English-language studies evaluating patients of all age groups diagnosed with head and neck cancer who underwent radiation therapy while receiving peritreatment steroids compared with those who did not receive steroids. RESULTS: Two retrospective cohort studies were identified for qualitative review. On the basis of analysis of 25 328 participants (36-82 years of age) with head and neck cancer who underwent radiation therapy, the use of peritreatment steroids was associated with a significantly lower risk for osteoradionecrosis in both studies, with a hazard ratio of 0.74 (95% confidence interval, 0.59-0.94; P = .012) and a relative risk of 0.04 (95% confidence interval, 0.003-0.560; P = .017). Meta-analysis was precluded by clinical and statistical heterogeneity. Overall, the studies were of limited quality with high risk for bias and poor methodology. CONCLUSIONS: Limited retrospective data suggest that steroids are predictive of a reduced risk for osteoradionecrosis; however, no definitive conclusions can be made given the poor quality of the available literature. Well-designed, comparison-controlled trials are needed to clarify the promising role of steroids in the prevention of osteoradionecrosis of the head and neck.

Comparison of multi-institutional pre-treatment verification for VMAT of nasopharynx with delivery errors.

PURPOSE: Measurement-based pre-treatment verification with phantoms frequently uses gamma analysis to assess acceptable delivery accuracy. This study evaluates the sensitivity of a commercial system to simulated machine errors for three different institutions' Volumetric Modulated Arc Therapy (VMAT) planning approaches. METHODS: VMAT plans were generated for ten patients at three institutions using each institution's own protocol (manually-planned at institution 1; auto-planned at institutions 2 and 3). Errors in Multi-Leaf Collimator (MLC) field size (FS), MLC shift (S), and collimator angle (C) of -5, -2, -1, 1, 2 and 5 mm or degrees were introduced. Dose metric constraints discriminated which error magnitudes were considered unacceptable. The smallest magnitude error treatment plans deemed clinically unacceptable (typically for a 5% dose change) were delivered to the ArcCHECK for all institutions, and with a high-dose point ion chamber measurement in 2 institutions. Error detection for different gamma analysis criteria was compared. RESULTS: Not all deliberately introduced VMAT plan errors were detected using a typical 3D 3%/3 mm global gamma pass rate of 95%. Considering all institutions, gamma analysis was least sensitive to negative FS errors. The most sensitive was a 2%/2 mm global analysis for institution 1, whilst for institution 2 it was 3%/3 mm global analysis. The majority of errors (58/59 for institution 1, 54/60 for institution 3) were detected using ArcCHECK and ion chamber measurements combined. CONCLUSIONS: Not all clinically unacceptable errors are detected. Combining ion chamber measurements with gamma analysis improved sensitivity and is recommended. Optimum gamma settings varied across institutions.

Intraoperative Cryoanalgesia for Reducing Post-Tonsillectomy Pain: A Systemic Review.

OBJECTIVE: Summarize the effectiveness of intraoperative cryoanalgesia in the management of postoperative pain among patients undergoing palatine tonsillectomy. METHODS: A systematic review of PubMED, MEDLINE, EMBASE, Google Scholar, and Cochrane trial registries was performed through January 2017 using the PRISMA standards. We included English-language randomized controlled trials evaluating patients of all age groups with benign pathology who underwent tonsillectomy with cryoanalgesia versus without. RESULTS: Three limited quality randomized controlled trials involving 153 participants (age range, 1-60 years) were included. Cryoanalgesia was performed with a cryotherapy probe (-56°C) in 1 trial and ice-water cooling (4°C to 10°C) in 2. In the 3 trials reviewed, patients who received cryoanalgesia reported 21.38%, 28.33%, and 31.53% less average relative postoperative pain than controls on the visual analog scale. Review of secondary outcomes suggested no significant difference in time to resume normal diet (2 studies) or postoperative bleeding (2 studies) between the 2 groups. Cryoanalgesia allowed patients to return to work 4 days earlier than controls in 1 study. Two studies reported a trend toward less postoperative analgesia use among the treatment group; however, no statistical conclusions could be drawn. CONCLUSION: The available evidence suggests that patients undergoing tonsillectomy with cryoanalgesia experience less average postoperative pain without additional complications.

Modern management of osteoradionecrosis.

PURPOSE OF REVIEW: Despite recent advances in radiotherapy, osteoradionecrosis (ORN) remains a common and difficult complication of radiation therapy in head and neck cancer patients. Available treatment options are complementary to its complex pathophysiology and the currently available theories of ORN development. The efficacy of hyperbaric oxygen therapy has recently been questioned, and therapies targeting the fibroatrophic process have become a focus of ORN treatment. The objective of this review is to evaluate the literature regarding ORN of the mandible, with a focus on available treatment options. RECENT FINDINGS: The recently proposed fibroatrophic theory has challenged the traditional hypovascular-hypoxic-hypocellular theory as the mechanism of ORN. Medical management targeting this fibroatrophic process offers promising results, but has yet to be confirmed with robust clinical trials. The routine use of hyperbaric oxygen therapy is not substantiated in the literature, but may be justified for select patients. Systemic steroids may also have a role, though data are limited. SUMMARY: The fibroatrophic process has gained acceptance as a main mechanism of ORN. No gold standard treatment or consensus guidelines exist, though a combination of therapeutic strategies should be considered, taking into account the severity of disease and individual patient characteristics.

Intraoperative Use of Desmopressin for Treatment of Profound Hyponatremia in the Setting of Emergency Surgery: A Case Report.

Correction of profound hyponatremia requires careful planning and close monitoring to reduce the risks of neurologic injury. Although there are various suggested treatment strategies in the setting of a medical ward or intensive care unit, reports of intraoperative management to prevent rapid increases in serum sodium are lacking. We present a case of profound hyponatremia of 102 mmol/L in a patient who required emergent operative repair for bowel obstruction. This is the first case to our knowledge that demonstrates a perioperative fluid and desmopressin treatment strategy to prevent overly rapid changes of sodium concentration in a patient with severe hyponatremia.

Association of Continued Preoperative Aspirin Use and Bleeding Complications in Patients Undergoing Thyroid Surgery.

IMPORTANCE: No evidence exists to direct the management of preoperative aspirin (acetylsalicylic acid) use in patients undergoing thyroid surgery. Nevertheless, a considerable number of patients interrupt receiving aspirin therapy during the preoperative period to minimize bleeding complications despite the increased risk of experiencing major adverse cardiac events. OBJECTIVE: To determine whether aspirin therapy continued preoperatively increases bleeding complications in patients undergoing thyroid surgery. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a consecutive sample of 570 patients, aged 18 to 100 years, who underwent thyroid surgery for benign and malignant disease from January 1, 2010, to December 31, 2015, by a single surgeon at a tertiary referral hospital center in New Orleans, Louisiana. EXPOSURES: Patients receiving aspirin therapy and patients not receiving aspirin therapy (aspirin naive) preoperatively. MAIN OUTCOMES AND MEASURES: Comparison of estimated blood loss, substantial blood loss, operative hematoma, nonoperative hematoma, and recurrent laryngeal nerve injury. RESULTS: Of 570 patients who underwent thyroid surgery, 106 (18.6%) were performed in patients receiving aspirin; of these, 23 (21.7%) were men and 105 (99.1%) were older than 45 years. Those receiving aspirin therapy displayed a 14.4-year difference in age (95% CI, 11.6-17.1). The aspirin group displayed a 20.3% absolute increase (95% CI, 9.3-30.7) in African American patients. Aspirin therapy was not associated with a statistically significant or clinically meaningful increase in intraoperative blood loss (2.5 mL; 95% CI, -0.4 to 5.3). Aspirin therapy was associated with a statistically significant increase in total hematoma formation (3.3%; 95% CI, 0.4-9.0), but the results were inconclusive. Aspirin therapy was not associated with a statistically significant increase in recurrent laryngeal nerve injury (2.6%; 95% CI, -1.1 to 8.6), but the results were inconclusive. CONCLUSIONS AND RELEVANCE: These results suggest that aspirin therapy can be maintained prior to thyroid surgery without increased intraoperative bleeding. Further research with a larger sample size and more outcome events are required to make definitive conclusions regarding the association between aspirin use and complications, including hematoma and recurrent laryngeal nerve injury.

A simple model for transit dosimetry based on a water equivalent EPID.

PURPOSE: The aim of this study was to demonstrate a new model for implementing a transit dosimetry system as a means of in vivo dose verification with a water equivalent electronic portal imaging device (WE-EPID) and a conventional treatment planning system (TPS). METHOD AND MATERIALS: A standard amorphous silicon (a-Si) EPID was modified to a WE-EPID configuration by replacing the metal-plate/phosphor screen situated above the photodiode detector with a 3 cm thick water equivalent plastic x ray converter material. A clinical TPS was used to calculate dose to the WE-EPID in its conventional EPID position behind the phantom/patient. The "extended phantom" concept was used to facilitate dose calculation at the EPID position, which is outside the CT field of view (FOV). The CT images were manipulated from 512 × 512 into 1024 × 1024 and padded pixels were assigned the density of air before importing to the TPS. The virtual WE-EPID was added as an RT structure of water density at the EPID plane. The accuracy of TPS dose calculations at the EPID plane in transit geometry was first evaluated for different field sizes and thickness of object in the beam by comparison with the dose measured using a 2D ion chamber array (ICA) and the WE-EPID. Following basic dose response tests, clinical fields including direct single fields (open and wedged) and modulated fields (integrated or control point by control point doses for VMAT) were measured for 6 MV photons with varying of solid water thickness or an anthropomorphic phantom present in beam. The EPID images were corrected for dark signal and pixel sensitivity and converted to dose using a single dose calibration factor. The 2D dose evaluation was conducted using 3%/3 and 2%/2 mm gamma-index criteria. RESULTS: The measured dose-response with the ICA and WE-EPID for all basic dose-response tests agreed with TPS dose calculations to within 1.5%. The maximum difference in dose profiles for the largest measured field size of 25 × 25 cm2 was 2.5%. Gamma evaluation showed at least 94% (3%/3 mm criteria) and 90% (2%/2 mm) agreement in both integrated and control-point doses for all clinical fields acquired by the WE-EPID and ICA when compared with TPS-calculated portal dose images. CONCLUSION: A new approach to transit dose verification has been demonstrated utilizing a water equivalent EPID and a commercial TPS. The accuracy of dose calculations at the EPID plane using a commercial TPS beam model was experimentally confirmed. The model proposed in this study provides an accurate method to directly verify doses delivered during treatment without the additional uncertainties inherent in modelling the complex dose-response of standard EPIDs.

Osteochondroma of the Hyoid: First Pediatric Case and Literature Review.

Osteochondromas, the most common benign bone tumors, are cartilaginous neoplasms of unknown origin with rare malignant potential. Osteochondromas rarely occur in the head and neck, and diagnosis relies on a combination of clinical, radiological, and histological criteria. Excision is often curative. We describe the first reported case of hyoid osteochondroma in an adolescent male with multiple osteochondroma, discuss its surgical management, and perform a review of the salient literature. Osteochondroma represents a rare diagnosis to include in the differential of any midline neck mass.

Invasive Insular Thyroid Carcinoma Presenting as Nonparalytic Dysphonia.

BACKGROUND: Patients with suspected thyroid malignancy often undergo preoperative laryngeal examination with a focus on vocal fold mobility. We present the unique case of a patient with invasive thyroid carcinoma who presented with dysphonia despite intact vocal fold motion. CASE REPORT: A 73-year-old female with a remote thyroid lobectomy presented with dysphonia. Thyroid ultrasound and fine-needle aspiration revealed a 1.1-cm nodule consistent with a colloid cyst. Videostroboscopy demonstrated mild laryngeal stenosis at the glottis and infraglottis with no evidence of paralysis. After failed medical therapy, the patient underwent microlaryngoscopy with biopsy of her infraglottic fullness, with histopathology reporting squamous epithelium without nucelar atypia. After several weeks of worsening dysphonia and persistent infraglottic fullness, she underwent repeat microlaryngoscopy with biopsy. On postoperative day 1, she developed dyspnea and stridor refractory to maximal medical management. To secure the airway, she underwent an awake tracheostomy, during which the thyroid isthmus was found to be densely adherent to the larynx. Histopathology identified insular thyroid carcinoma. Subsequent imaging confirmed a large, invasive thyroid tumor. Further workup revealed metastases to the bone and liver. The patient underwent a successful palliative resection of the thyroid followed by neck radiation and received palliative spinal surgery with adjuvant radiation. A clinical trial of vandetanib was initiated but withdrawn because of myelosuppression. She deferred any further treatment and was alive with few symptoms despite persistent disease 1.5 years after initial diagnosis. CONCLUSION: Physicians should consider the diagnosis of invasive thyroid carcinoma in a dysphonic patient with an infiltrative endolaryngeal process despite intact vocal fold mobility.