OtoLaryngology New Articles

Reproducibility between mRNA RT-PCR and mRNA ISH in OSCC patients—reply Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): Patrizia Morbini, Paola Alberizzi Read More » Sarcina: the eyes see what the mind knows Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): Abhijit Chougule, Amanjit Bal Read More » Concordance study between OSNA and morphologic techniques to detect lymph node metastasis in papillary carcinoma of the thyroid Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): Sofía del Carmen, Sonia Gatius, Guzmán Franch-Arcas, José Antonio Baena, Oscar Gonzalez, Carlos Zafon, Dolors Cuevas, Joan Valls, Angustias Pérez, Mercedes Martinez, Susana Ros, Carmen García Macías, Carmela Iglesias, Xavier Matías-Guiu, Enrique de Álava Tumor resection in papillary thyroid carcinoma (PTC) is often accompanied by lymph node (LN) removal of the central and lateral cervical compartments. One-Step Nucleic Amplification (OSNA) is a polymerase chain reaction (PCR) based technique which quantifies Cytokeratin 19 (CK19) mRNA copies. Our aim is to assess the value of OSNA in detection of LN metastases in PTC, in comparison with imprints and microscopic analysis of formalin-fixed, paraffin-embedded tissue (FFPE). A total of 387 LN from 37 patients were studied. From each half LN, 2 imprints were taken and analysed with hematoxylin and eosin (H&E) and CK19 immunostaining. One half of the LN was submitted to OSNA and one half to FFPE processing and H&E and CK19 staining. For concordance analysis, every single LN was considered as a case. A group of 11 cases with discordant results between OSNA and H&E/CK19 FFPE sections were subjected to additional FFPE serial sectioning and H&E and CK19 staining. We found a high degree of concordance between the assays used, with sensitivities ranging from 0.81 to 0.95, and specificities ranging from 0.87 and 0.98. OSNA allowed upstaging of patients from pN0 to pN1, in comparison with standard pathological analysis. Identification of a metastatic LN with more than 15.000 CK19 mRNA copies predicted presence of a second LN with macrometastasis (<5.000 copies). In summary, the study shows that OSNA application in sentinel or suspicious LN may be helpful to assess nodal status in PTC patients. Read More » Polyoma Virus Large T Antigen Is Prevalent in Urothelial Carcinoma Post Kidney Transplant Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): Ling Yan, Mohamed E. Salama, Christian Lanciault, Linh Matsumura, Megan L. Troxell Viral pathogens have been associated with both infectious disease and neoplasia in transplant recipients. Polyomavirus is emerging as a potential causative agent for genitourinary tract cancer in post kidney transplant patients. Human papilloma virus (HPV) has a proven role in squamous cancers, but has not been studied in genitourinary malignancies in transplantation. Of 2345 kidney transplants performed at our center over the past 20 years, we identified 16 patients with 20 genitourinary cancers (0.7%), including 13 bladder/ureter carcinomas, 5 renal cell carcinomas (RCC) and 2 prostate carcinomas. We performed immunohistochemical staining for polyoma virus Large T antigen, and p16, followed by in-situ hybridization for HPV in p16+ cases. Four cases of high grade invasive urothelial bladder carcinomas were positive for LargeT. LargeT+ urothelial carcinomas developed ≥ 8 years post-transplant in young men, 3 with history of BK polyoma viremia, two of whom had native kidney failure due to reflux/obstruction. In situ hybridization for high-risk HPV was negative in all tested cases. Overall, 3 patients died of carcinoma. All 5 RCCs were negative for both LargeT and p16; two prostate cancers were p16 negative, and p16+/HPV-negative respectively. Thus, our study shows relatively high prevalence of Large T antigen in urothelial carcinoma in kidney transplant patients (30%), but not in RCC. Although sample size is small, young patients with obstructive disease may be at particular risk to develop LargeT positive urothelial carcinoma. Overall, our data further support the necessities of long-term cancer surveillance for renal transplant patients. Read More » Reproducibility between mRNA RT-PCR and mRNA ISH in OSCC patients Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): Chiara Maura Ciniselli, Chiara C. Volpi, Barbara Cortelazzi, Ambra V. Gualeni, Stefano Bottelli, Federica Perrone, Silvana Pilotti, Annunziata Gloghini, Paolo Verderio Read More » Vascular Mesangial Channels in Human Nodular Diabetic Glomerulopathy Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): L. Nicholas Cossey, Randolph A. Hennigar, Steve Bonsib, Alan M. Gown, Fred G. Silva The presence of vascular mesangial channels has been reported in idiopathic nodular glomerulosclerosis and diabetic glomerulopathy. However, only limited information on the morphology and immunohistochemical phenotype of these channels is available. This study aims to describe the light and electron microscopic features of these channels and delineate their immunohistochemical phenotype. Thirty-eight cases of human nodular diabetic glomerulopathy with mesangial channels identified by light microscopy were prospectively selected (2010–2012). The cases were stained with CD31/PAS combined stain. Selected cases were immunostained for CD34, podoplanin, ERG and Ki-67. Frequent, small and peripheral vascular mesangial channels were seen in all cases while larger and more centrally located vascular channels were also observed. Communication between peripheral capillary loops and peripheral vascular mesangial channels was seen as was communication between peripheral and central vascular mesangial channels. The vascular mesangial channel lining cells showed a typical endothelial phenotype with strong expression of CD31, CD34 and ERG by immunohistochemistry. The lymphatic channel marker podoplanin was negative in all channels and the proliferation marker Ki-67 showed no evidence of increased proliferation. By electron microscopy mesangial channels show angulated, irregular borders with lining cells compatible with endothelium and surrounded by mesangial matrix. No basement membranes were identified surrounding the mesangial channels. These findings support the existence of vascular mesangial channels in nodular diabetic glomerulopathy and suggest neovascularization and altered blood flow within these glomeruli. Read More » Acute Oxalate Nephropathy Due to Pancreatic Atrophy in Newly Diagnosed Pancreatic Carcinoma Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): Irfan Moinuddin, Asif Bala, Butool Ali, Husna Khan, Erika Bracamonte, Amy Sussman Acute oxalate nephropathy can occur due to primary hyperoxaluria and secondary hyperoxaluria. The primary hyperoxalurias are a group of autosomal recessive disorders of endogenous oxalate overproduction. Secondary hyperoxaluria may occur as a result of excess dietary intake, poisoning with oxalate precursors (ethylene glycol) or enteric hyperoxaluria. The differential diagnosis of enteric hyperoxaluria includes inflammatory bowel disease, short bowel syndrome, bariatric surgery (with jejunoileal bypass or Roux en Y gastric bypass), celiac disease, partial colectomy and chronic pancreatitis. The common etiology in all these processes is fat malabsorption, steatorrhea, saponification of calcium, and absorption of free oxalate. Hyperoxaluria causes increased urinary oxalate excretion, urolithiasis (promoted by hypovolemia, decreased urinary pH caused by metabolic acidosis, and decreased citrate and magnesium concentrations in urine), tubulointerstitial oxalate deposits and tubulointerstitial nephritis. We report a rare case of acute oxalate nephropathy due to pancreatic atrophy and exocrine insufficiency caused by newly diagnosed pancreatic cancer. Read More » Follicular Pancreatitis: A Distinct Form of Chronic Pancreatitis - An Additional Mimic of Pancreatic Neoplasms Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): Rajib K. Gupta, Bill H. Xie, Kurt T. Patton, Mikhail Lisovsky, Eric Burks, Stephen W. Behrman, David Klimstra, Vikram Deshpande Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, kappa and lambda light chains as well as IgG4 and IgG were performed. We found a total of six patients (male:female = 2:1, mean age = 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis while two presented with abdominal pain, fatigue and elevated liver enzymes. On imaging, three patients had a discrete solid mass while 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2 negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis or granulocytic epithelial lesions. IgG4/IgG ratio was <40% in all 6 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. Read More » hASH1 is a specific immunohistochemical marker for lung neuroendocrine tumors Publication date: Available online 3 October 2015 Source:Human Pathology Author(s): Bo Ye, Jaclyn Cappel, Jennifer Findeis-Hosey, Loralee McMahon, Qi Yang, Guang-Qian Xiao, Haodong Xu, Faqian Li Mammalian/human achaete-scute homolog 1 (m/hASH1) regulates neuroendocrine cell development. No detailed comparative study has been conducted to explore the immunohistochemical utility of hASH1 in distinguishing different types of lung cancers. We investigated the expression of hASH1, synaptophysin, chromogranin, and CD56 in 101 squamous cell carcinoma (SCC), 183 adenocarcinoma (ADC), 37 typical carcinoid (TC), 14 atypical carcinoid (AC), 11 large cell neuroendocrine carcinoma (LCNEC), and 24 small cell lung carcinoma (SCLC) of the lung by immunohistochemical staining with a monoclonal antibody against hASH1. Staining intensity was graded from 0 to 3 and percentage of tumor cells in each grade was estimated. All cases of ADC and SCC were discreetly negative for hASH1 in contrast to their low percentage positivity for synaptophysin, chromogranin, and CD56. hASH1 positively stained TC (64.9%), AC (64.3%) , LCNEC (72.7%), and SCLC (79.2%) as chromogranin (TC, 100%; AC, 78.6%; LCNEC, 9.0%; and SCLC, 4.2%), synaptophysin (TC, 100%; AC, 78.6%; LCNEC, 81.8%; and SCLC, 83.3%), and CD56 (TC, 59.5%; AC, 57.1%; LCNEC, 36.4%; and SCLC, 79.2%). TC and AC often showed weaker intensity and lower percentage of tumor cells positive for hASH1 (median score 5) than LCNEC and SCLC (median score 40 and 170 respectively). There were statistically significant differences in mean intensity scores between SCLC (148.8±20.1) and other neuroendocrine tumors(NE): TC (37.1±9.2) and AC (28.6±10.8) or LCNEC (51.8±18.0). Our findings indicate that hASH1 is a specific marker to distinguish NE from SCC and ADC. Additionally, hASH1 is a useful diagnostic marker for segregating SCLC from others NE. Read More » Consensus on Establishing an Oral Appliance Starting Position (Steve Lamberg, Harry Ball, Steve Carstensen, Christopher Kelly, Mark Collins, Barry Glassman, Erin Elliott, Kent Smith, Shouresh Charkhandeh, Rob Burwell, Todd Morgan, Daniel Klauer, Dennis Marangos, Tim Mickiewicz, Gina Pepitone-Mattiello, Stephen Gershberg, Tony Soileau, Richard Reichman, Dan Tache, John Viviano) The LinkedIn Discussion Group, "SleepDisordersDentistry" has just completed an open discussion on establishing an Oral Appliance Starting Position. Here is a consensus for all to ponder. What was asked,  "Our next discussion will be "Establishing Oral Appliance Starting Position". We've already heard a great deal from both the Phonetic and George Gauge Groups, but there are many other approaches and ideas such as the Apnea Guard, Airway Metrics, Andra Gauge, MATRx etc. I have even heard of clinicians using a "Golf Tee" to establish their initial bite registration! There is very little in the literature about "Establishing Oral Appliance Starting Position"; so it would be very interesting to hear about various techniques and methods, and what works for clinicians around the world…" What was said, Our discussion on "Establishing an Oral Appliance Starting Position" confirms much agreement amongst our peers that there is no universal "Evidenced Based", or "Anecdotally Based" starting point that will assure the best outcome; most clinician's relying on the only Evidenced Based Data, "Jaw Advancement" while keeping "Vertical to a Minimum". However a scattering of very unique ideas were also discussed, including some new Evidence Based technologies that provide valuable information regarding both efficacy and starting position. Our longest discussion to date included some very heated posts, that were at times entertaining, at other times insightful and occasionally could be considered an outright "cyber" fistfight. I encourage you to take the time to review the following synopsis on the many ideas expressed by clinicians that actually do this work on a daily basis in their clinics.  Mandibular advancement: The majority of discussion revolved around some degree of mandibular advancement (the only Evidence Based approach). As a starting point, most clinicians advance the mandible approximately 60-70 % of the protrusive range, and then make various "Consideration Adjustments" from that position which results in the final "Starting Position". The various "Consideration Adjustments" mentioned were: Patient comfort (trumps all) Results of muscle, ligament and joint palpation exams Appliance design, (ensuring that the selected position still enabled the patient to reach their maximum protrusive position when considering the chosen appliances unique adjustment range, keeping in mind that for some patients, protrusive range increases with appliance wear) Apnea Severity (less advancement for less severe apnea) Urgency to obtain optimum outcome Once a position is established, Barry Glassman discussed having the patient clench their teeth in the George Gauge, and then go to each lateral position and have the patient clench again, looking for tenderness or tightness in the contralateral joint. If this tests positive, a less (or more) protruded position would be established, followed by retesting. It was pointed out that this 60-70% of protrusive position has little science behind it, so it makes more sense to work back from maximum protrusive based on the unique adjustment range of the chosen appliance as a start position, and then make the "Consideration Adjustments". I found the drama over this part of the discussion quite entertaining. When one considers what 60-70% of a "typical" range of motion is, and how it compares to the position you end up with when you work back from maximum protrusive by the amount of adjustability of a "typical" appliance (approximately 5mm), the two positions of course vary, but are somewhat similar, yet this resulted in so much debate! What made this part of the discussion even more entertaining was that pretty well everyone agreed that this final position would be tweaked further, based on the "Consideration Adjustments". Quite frankly, especially once you consider the "Consideration Adjustments ", I don't see any material difference between these two approaches for the majority of people. Just do the math and you'll see what I mean. Just sayn';). Kent Smith said it best and with the most honesty, "Hey, it's all a guess anyway!" So, in the end, it seems clinicians in this group advance the mandible using a set formula (which often results in a similar position for all) and then adjust that position forward or back based on certain "Consideration Adjustments" to establish the Starting Position. It was also pointed out that some patients experience maximum benefit by simply preventing the jaw from falling back, with no forward protrusion at all. However, the bite position should be advanced a minimum of 1 to 2 mm from "centric" to prevent translation/rotation out of appliance as advancement decreases the opening potential (particularly useful with the dorsal design). For patients overly concerned about possible bite changes, it was suggested that less advancement be considered. A study conducted by Doff et al. March 2013 "Long Term OA Therapy in OSAS", documented the following, "Linear regression analysis revealed that the decrease in overbite was associated with the mean mandibular protrusion during follow-up [regression coefficient (beta) = -0.02, 95 % confidence interval (-0.04 to -0.00)]"; suggesting that this type of tooth movement could be minimized with less advancement.  Although there are various tools available to facilitate taking a mandibular advancement bite registration (George Gauge, Pro Gauge, Andra Gauge etc), it seems that the George Gauge with the 2 mm bite fork was the most common tool used. The 5 mm bite fork was recommended when an increased vertical was sought. Modification to the George Gauge was also mentioned; placing wax in the "V" groove to increase the vertical and drilling out the "V Groove" so it better accommodates misaligned teeth. Whichever tool is used, it was recommended that the patient not clench into it when taking the bite registration. (John Viviano, Steve Lamberg, Harry Ball, Steve Carstensen, Christopher Kelly, Mark Collins, Barry Glassman, Erin Elliott, Kent Smith) Vertical Alterations: Right off the bat, I feel it is worthwhile to mention that the variety of appliances currently available range widely in Vertical, yet there is no evidence in the literature that one appliance results in a superior outcome to another. Moreover, there is very little research on vertical and it mostly supports keeping it to a minimum (Petsis, 2002). However, anecdotally, it seems that a subset of patients benefit from varying vertical. In approximately 2005, even Alan Lowe came forward on this issue and after years of stating that the vertical should be kept to a minimum, he admitted that in a subset of patients, an increase in vertical results in a better outcome. However, personally I have been less concerned with altering vertical since moving to appliances that don't restrict the patient to a particular vertical, allowing them to naturally gravitate to their preferred vertical; a theory I have pondered for a while. Having said this, I recently placed a 2mm "V" Tab spacer on a Narval I am using to manage a very obese, very severe apneic and the initial subjective response is a notable improvement, in the patient's words, "this position is 100 times better", we'll see how things play out for him (Confirmation Bias? Not sure). Maybe there is something to the notion of lifting the lid of the box the tongue is in to make more room for it (thanks Todd). The same phenotyping criteria explained in our Vertical discussion was repeated, men need more vertical, women less, obese more, and non-obese less. Using a slightly higher vertical for those with poor nasal patency was also discussed, the theory being that these individuals tend to mouth breath and the increase in vertical may facilitate that process. Of course, we are talking about anecdotal observations here. Todd Morgan shared with us his Evidence Based research on vertical that resulted in the development of the Apnea Guard (discussed in detail below). Todd says, "Theoretically, adding VDO may improve upper airway dynamics by one or two routes: 1) By putting the hyoid sling musculature under additional tension, primarily via the stylohyoid and styloglossus muscles, or 2) By increasing a phenomena known as tracheal tug. My assumptions are based on the dynamic interaction of the infra and supra hyoid muscles and observation on lateral imaging that demonstrates a "smoothing" of the pharyngeal mucosal outline. Whatever the mechanism, we have found in clinical practice that VDO acts as a surrogate to further protrusion in bringing down the supine AHI." In a current study, Todd is comparing outcomes with patients wearing the low, medium and high Apnea Guard trays, all advanced to 70% protrusion. This should be interesting. One clinician establishes vertical using the following phenotype characteristics. If the patient has a large maximum opening, large chin and strong bite he uses an 8mm vertical, provided the patient can comfortably manage that vertical. He uses the Airway Matrix system in taking his bite. Of course, this is not Evidence Based. Another device that can be used to facilitate varying vertical is the Andra Gauge. So, the majority of clinicians start their process with the notion that vertical should be kept to a minimum, which is the default literature position, establishing a vertical incisal edge-to-edge opening of 2-3 mm. A subset then increase vertical from there, based on the vertical required by the chosen appliance, evaluations using tools such as Airway Metrics, Andra Gauge, pharyngometry etc, or insights derived by clinical or anecdotal observations of verticals associated with superior outcomes for particular phenotypes. As a caution for all this vertical alteration, it was discussed that increasing vertical has the potential of creating increased strain or sprain of the ligament attachments, especially with and during para-function. So, if you are considering altering vertical, it would be wise to "Alter vertical with Care and in Small increments". (John Viviano, Steve Lamberg, Christopher Kelly, Mark Collins, Barry Glassman, Todd Morgan) Airway Evaluation: Evaluating the airway using Acoustic Reflection and CBCT was also discussed. Of course, of the two, Acoustic Reflection is the less intrusive. Despite the fact that there is no literature tying improvement in the airway as evaluated by these devices during wakefulness to actual improvements of airway behavior during sleep, there are many clinicians that find this evaluation a useful adjunct in establishing their appliance start position. The use of Pharyngometry to evaluate benefits of varying vertical was also discussed. Regarding CBCT, of course, the major concern was excessive radiation exposure and the lack of Evidenced Based rational for its use to establish the starting position for a sleep apnea appliance. (Dan Tache, Dennis Marangos, Tim Mickiewicz, Christopher Kelly, Mark Collins, John Viviano, Barry Glassman) MATRx: We had the good fortune of having Shouresh Charkhandeh (over 500 MATRx cases) share his insights with us. Quite frankly, these insights have me very excited about what this remote control technology has to offer our field. Unfortunately, there was not much discussion by varying clinicians about this relatively new approach. Perhaps, due to how little it has penetrated the marketplace, approximately 150 centers across North America. It is extremely unfortunate that the current MATRx business model does not fit with the way Sleep Medicine works. It requires everyone involved doing the "Right Thing" and that is simply asking a bit much. If Sleep Medicine were practiced in that manner, many more appliances would be prescribed than is currently the case. However, recently, I heard about the next generation of this device that will put the MATRx in the Dentist's hands, allowing a Dentist to do the same evaluation in the patient's home, much how we currently use Home Sleep Tests (HST) to help calibrate our appliances (ETA approximately 18 months). This has me very excited for the same reason I routinely use a HST to help calibrate my appliance; it will simply up my game. I suspect that we will receive the same level of push back from the Physicians as we currently have regarding our use of HST, even though we are not using HST to screen, diagnose or establish "Official" efficacy. The reasons for this pushback are transparent and not in the patient's best interest. However, I will continue to use HST as long as it is legal for me to do so under my licensure because quite frankly, it helps me do a better job, the same will apply to the Portable MATRx when it becomes available to me. At a recent conference, I shared the following with John Remmers, "when the mobile version of this device becomes available, make sure my name is first on the list, I'll buy it site unseen". The importance of establishing a good "work flow" with the Sleep lab was discussed and Shouresh pointed out that the upfront time spent with the lab to ensure a good "work flow" pays off once everyone knows what they are doing. It was also pointed out that this protocol advocates moving directly to the "Sweet Spot", much like the protocol used with CPAP titration. Personally, I question what impact this may have on patient "adherence". One of the major differences between the way Dentistry and Medicine approaches these patients is our connection with the patient and concern for their comfort and ability to "actually wear" their device. I don't think we have come to have a much higher "adherence" rate than CPAP by accident; we have earned it, and I question whether it would remain as high if patients were expected to wear their appliance in the final position from the get go. Having said that, Shouresh shares with us that he routinely (85% of the time) goes right to the sweet spot. He does this when the target position is less than 80% of protrusive range, and reports that patients manage this with very little in the way of the side effects that some (including myself) would be concerned about. I find this very interesting. Perhaps the benefit of going to the "Sweet Spot" immediately which results in an "immediate" resolution of the OSA, reduces the typical side effects we experience when we work towards the most effective position in a step wise fashion; I would never of thought that. If the final position is between 80-100%, Shouresh starts them at 70-80% and asks them to titrate to the AP position provided by the test over a few weeks. Shouresh points out to us that "the MATRx is not a bite technique, it is a test that identifies responders to OAT (prior to making an appliance) and more importantly gives the clinician/dentist an objective data on how the patient's passive pharynx/ airway responds to mandibular protrusion (during sleep); which could then be used as another additional info to help treatment plan properly. It also provides you with an AP position for the responders, at which the patient's respiratory events/AHI will be well controlled (50% reduction AND below 10). Once I know the patient is going to respond to OAT, I will focus on the bite registration and starting point. Here are some of the factors that should be taken into consideration when doing the bite registration, to make an appliance comfortable; Vertical, Lateral, AP, Yaw, Pitch, Roll, Muscles, Lip Competency, arch form, any internal derangement, … and many more, to make the appliance anatomically and physiologically correct. This can be achieved through many techniques (most of them have been discussed already in this discussion), depending on the dentists training and occlusal philosophy and most importantly patient's characteristics. My personal preference is what I call Dynamic techniques; any technique that takes patients muscles and physiology into consideration (Phonetic bite, NM technique / TENS / EMG's) and is not just based on hard anatomical landmarks (such as Conventional use of George Gauge at 50-70%)" I simply quoted Shouresh here because he so eloquently summarized so much in so few words that it would be criminal to change it up. Shouresh also explained that he uses the MATRx to establish the level of protrusion (not a specific point, but rather a zone) and then takes a bite with his choice of method, which may or may not involve varying vertical. He also shared that their studies show that the AP position (% protrusion) is independent of patient's baseline AHI and BMI, ranging from almost no protrusion, to 100% in some cases, with "Median" being about 70%. These statistics suggest that half of the patients we are currently treating do not require the commonly used 70% protrusion, so we are essentially over-protruding half of our patients, potentially causing unnecessary side effects. Using the MATRx protocol helps avoid making an appliance for non-responders helps to ensure the patient is not protruded more than necessary, and negates the need to titrate appliances based on symptom relief, which is the current "standard of care". Knowing the optimum position upfront also allows Shouresh to better treatment plan his cases. He finds that certain designs/appliances work better at different levels of protrusion, a process he refers to as "Position Based Design". He also points out that patients requiring 90-100 % protrusion that also demonstrate an inability to maintain that position, are best steered away from an oral appliance. In essence, the MATRx helps to identify responders and reduces titration efforts (time). This is particularly important when considering that it establishes responders that have severe OSA that may not typically have the opportunity to try an appliance until they have already failed CPAP. Currently, about 5% of patients end up with an oral appliance. With MATRx establishing that 50% of patients tested are responders, if used routinely, this protocol has the potential to increase patients treated from 5 to 50%. He also points out that it does not have to be a "yes" or "No" tool. Even non-responders can be offered an appliance if they are CPAP intolerant to obtain some level of relief or to consider "Combo OA-PAP" therapy. Finally, ~60% of severe patients are positive responders; typically (without MATRx) these patients would not be offered OAT as a first line of therapy. Shouresh explains his clinics protocols as follows: MATRx for anyone with AHI of over 10 or high risk/very symptomatic If "non-responder", recommend CPAP-trial as first option and then OAT Patient can try CPAP, if non-compliant, they can still have an oral appliance The MATRx protocol simply helps place the options in the right order based on objective data. All patients are offered a choice of CPAP or OA regardless of their AHI, if they choose an OA, then a MATRx is prescribed. For patients non-compliant to CPAP the benefit of the MATRx is confirmation that the OA will work, often helpful in having the patient committing to the fee which may not be covered by insurance. The MATRx is not designed to replace anything. It is designed to improve patient care, and be used as a tool by a well-trained clinician. Just like any other technology, it is only as good as the information provided and the user. (Shouresh Charkhandeh, Rob Burwell, Erin Elliot, John Viviano, Steve Lamberg, Barry Glassman) Apnea Guard: Another "Evidence Based" approach for establishing an appliance starting position was discussed by Todd Morgan, the Apnea Guard. An article comparing the recommended Apnea Guard protocol to the conventional jaw advancement approach (which involves systematically advancing the jaw over a period of time), can be found HERE The Apnea Guard protocol demonstrates clinical utility for the following circumstances; immediate treatment of OSA while the patient is waiting for their custom device, post surgery, and to predict the correct starting position of an oral appliance. Please keep in mind that this study involved just 30 subjects, which begs for the need of further research involving a larger "n". This study demonstrates that Apnea Guard protocol performed with equivalency to custom appliance therapy when using the algorithm that correctly predicts the optimal starting position using both vertical and protrusive components. It also demonstrated that use of the Apnea Guard provides savings in patient follow-up appointments and overhead expenses by reducing the number of in-office visits prior to establishing an endpoint position. Of course, these savings are based on the conventional slow titration towards the "sweet spot" and become insignificant if the same aggressive approach is taken with a custom appliance as the protocol used with the Apnea Guard. Todd, like Shouresh above, also discussed the notion of jumping right to the 70% protrusive position from the get go, and that this more aggressive protocol seemed to result in fewer complications and side effect complaints, his theory being that a patent airway is the key to reduced muscle tone and improved comfort. Case studies have reported that oral appliance efficacy diminishes after a period of time at 60% protrusion, necessitating subsequent advancement. This research found that the Apnea Guard at 70% protrusion resulted in a similar result as the conventional progressive advancement method in 80% of cases. Future studies will compare the impact of initiating therapy at 60% vs.70% protrusion and how this relates to reports of morning muscular discomfort. The timing of when to perform the efficacy outcome study also requires further consideration. First night of therapy sleep studies may be useful in identifying patients who respond to oral appliance therapy, but it is unclear whether these initial results can also establish that the appliance has been optimally calibrated. The Apnea Guard is limited to 30-nights of use based, in part, on the assumption that patients with no contra-indications can safely wear it for a short duration. One of the concerns about using a trial appliance such as the Apnea Guard is that patients may get a "wrong and negative" impression of the comfort of a custom oral appliance. Patients in this study did find the custom appliance more comfortable, but actually preferred the Apnea Guard to no therapy. The authors stressed that to avoid a negative bias toward OAT developing during the trial period, patients need to be educated that custom appliances are more comfortable and that excessive salivation during sleep will subside. Studies are underway to demonstrate that the "Efficacious" Vertical and Protrusive setting of an Apnea Guard, captured by extracting the retention material used for the bite registration from the appliance, can be used as a bite registration in the fabrication of a custom appliance, that results in continued efficacy; potentially reducing the customary calibration efforts and also facilitating the efforts of a less experienced clinician to provide effective therapy. Of course, patients can continue using the Apnea Guard by simply refitting it with a second set of retention material for use while they are waiting for their custom appliance to be fabricated. For those patients that hesitate to proceed without some evidence of efficacy, this device could provide that evidence, and result in the actual construction bite. Something other temporary appliances do not do. Also, for those clinicians that use an appliance that cannot be easily altered from a vertical perspective (like Nylon 3D printed appliances), this device allows one to evaluate the impact of vertical prior to making the custom appliance. Another thing I particularly like about this device is that you are getting information based on the "normal" sleep experience, in the comfort of the patient's own bed. Much more meaningful than what you get in a sleep lab setting. Pair it up with a HST and I think some extremely valuable information can be obtained. I have some in my office now and I am going to selectively try this protocol out. We'll see how smoothly it goes.  (Todd Morgan, Barry Glassman, John Viviano) Phonetic Bite: The Phonetic Bite group re-confirmed that their start position, is usually at or within 1-2mm of their end position. This starting position is where the phonation takes the mandible to during speech (when counting from 60-75). Adjustment Considerations include patient overbite and how much vertical is needed to accommodate the appliance of choice. It is claimed that this approach results in a comfortable position for most because it's a position that the patient is accustomed to taking throughout the day when they speak. The claim is that this bite position rarely if ever results in complaints of TMJ discomfort. When I observe a clinician taking a Phonetic Bite, it looks like somewhat of a "slight of hand" parlor trick that results in a bite that is then altered depending on vertical needed by the appliance design. Although it is really hard for me to understand how this could possibly be related to the airway, and have doubted it for years, I have now seen objective proof of it working! Daniel Klauer and I are involved in an investigation of 20 retrospective consecutive patients treated with a appliance fabricated using a Phonetic Bite compared to 20 retrospective consecutive patients treated with an appliance fabricated using a usual and customary jaw advancement protocol; both resulted in the same outcome, based purely on reduction in AHI, imagine that! Of course, this can only be considered a pilot study and says nothing about the claims of fewer side effects associated with a Phonetic Bite Protocol. So, more work is needed here, both with a larger number of patients, and documentation of short and long-term side effects so proper statistics can be performed. Notwithstanding this, it simply amazes me that the jaw brought to two VERY different locations, results in a similar drop in AHI (no statistical difference). (Daniel Klauer, Dennis Marangos, John Viviano) Over the Top Diagnostics: Jaw Tracking, Joint Vibration Analysis and CBCT's were also discussed to help establish the best starting position. Notwithstanding the absence of Evidence Based Literature to support the use of these procedures and techniques for this purpose, a number of clinician's stated that they aide in establishing a better starting position; their view on this is that the literature will catch up. To these clinicians I ask the following question, "If you were being treated for a medical condition by a Physician, would you prefer that the Physician used protocols that were solidly supported by Evidenced Based literature, or would you be OK with the Physician simply doing what he thought best? I know which I would prefer." A strong "Caution" was made about the notion of representing the use of a CBCT to be "Standard of Care" in assessing the TMJ for potential future issues, or to establish potential "Efficacy" when making a Sleep Apnea Appliance. These are simply not Evidence Based Claims. To clarify, a "Usual and Customary" screening for TMD is the "Standard of Care" in evaluating the TMJ for potential future issues, and currently, there is no Evidenced Based methodology to image the airway during wakefulness that can be used to determine appliance efficacy during sleep. PERIOD! (Dennis Marangos, Tim Mickiewicz, John Viviano, Barry Glassman) Drug Induced Sleep Endoscopy:  The use of Drug Induced Sleep Endoscopy to aide in establishing the best starting position was discussed. The consensus being that although this can be useful for research, it is not practical for regular patient care. (Gina Pepitone-Mattiello, Steve Lamberg) Muscle Relaxation and Reduction of Inflammation: The notion that deprograming the patient's customary and habitual bite through physiotherapy plays a role in establishing the best initial bite registration was discussed. The "theory" being that the patient's "comfortable normal bite" may not be a "healthy bite". If certain muscles such as the pterygoids are not balanced and one side stays contracted or fires slower it causes the jaw to rotate in a yaw plane. Taking a bite registration without correcting for this potentially locks them into a comfortable but unhealthy bite with the sleep appliance. By implementing a regimen of physiotherapy prior to taking the initial bite registration, a "Balanced Muscle Bite" can be established. Physiotherapy is also conducted at appliance insertion, the net result, side effects appear to be minimized and the patient maximum range of motion appears to increase. When considering this clinician's approach one should also consider that he uses a Mosses bite, and provides a Mosses appliance. Not much play with this appliance in the mouth and perhaps these concerns may be more about the choice of appliance (Monoblock like). Tony published an article explaining his modified Mosses Bite Technique on the American Sleep and Breathing Academy website for those that wish to read more about it HERE. Also, for those interested in watching a video of Dr. Moses demonstrating how to take a Mosses bite, this can be viewed online at: After viewing this video Steve Lamberg asked, "How does establishing the most comfortable vertical and protrusion translate into the best starting position?" The absence of both "Science" and "Logic" makes this a stretch for many to believe. Yet, patients are effectively managed using this bite registration! The point was made that it depends on how you define the "Best Starting Position", is it the best for "Patient Comfort", or for "Efficacy?" An argument was made that if one uses the "Best" starting position that is defined as being "Most Effective", but the patient can't tolerate wearing the appliance, that would in fact be the "Worst" starting position, not the "Best" starting position. The use of Low Level Lasers and the "Aqualizer", a self-adjusting oral splint were also discussed; both used to help "relax" the TM joints, reduce inflammation and muscle tension prior to taking a bite registration. Information on the Aqualizer can be found at: http://www.aqualizer.com Of course, this entire discussion on muscle relaxation and reduction of inflammation is completely anecdotal. With the number of variables involved, it is very difficult to evaluate this with proper research. Factors such as type of bite registration, degree of advancement, efficacy of therapy, appliance design, are just some of the variables potentially influencing what one will observe when investigating these issues. The good news, there is no evidence that you can do any harm with these techniques. (Tony Soileau, Dennis Marangos, John Viviano, Steve Lamberg, Barry Glassman) Pharyngometry and Rhinometry: Use of the pharyngometer coupled up with the Airway Metrics system was discussed, enabling the evaluation of both vertical opening and mandibular advancement. Use of the SnoreScreener to help isolate a position (both vertical and advancement) that results in the best resolution of snoring was reviewed, and use of the pharyngometer to evaluate the effect of the chosen position on the airway volume. Of course, these concepts are not Evidence Based, but some clinicians find them helpful in establishing their start position. Evaluation of the nasal passages with a Rhinometer to establish nasal patency was also discussed. The Acoustic Rhinometer is literature validated for this purpose and can be used along with a nasal decongestant to determine if poor patency is caused by bone or soft tissue. However, for our purposes as Dentists, that will not be treating the issue but rather screening for it, simply, placing your finger on one nostril and asking the patient to breath through the other, one nostril at a time, coupled up with a few strategic questions would likely provide you with all the information you need to make a referral. Performing the Cottle Maneuver can help to establish those individuals that may benefit from a simple nasal valve dilator, as oppose to those that may have a more serious problem requiring surgical intervention by an ENT. You can watch it being performed by clicking the following Link: Nasal Valve Dilators can be viewed at this website: https://www.maxairnosecones.com. If the Cottle maneuver does not make a difference, middle turbinate hypertrophy and/or polyps or perhaps septal deviation and/or allergies might be the issue necessitating an ENT referral. (Christopher Kelly, Richard Reichman, Dan Tache, Dennis Marangos, Mark Collins, Barry Glassman, Stephen Gershberg) Discussion:  There has been much discussion about using measurements or evaluations of the airway during wakefulness to predict how it will behave during sleep. However, to date, there is no Evidence Based literature to support these notions, regardless of the technique used. Interestingly, even the MATRx approach, which evaluates the airway during sleep, results in both false positives and false negatives. Regarding musculature, all sorts of devices and techniques were discussed to help the patient deal with wearing an oral appliance with minimal untoward side effects. What was said: The correct "Cant", established with the Phonetic Bite, results in fewer TMJ related and muscular side effects Muscular physiotherapy and treating the musculature with a laser or Aqualizer prior to taking a bite registration results in fewer patient pain and comfort issues Remarkably, we have clinicians not doing these procedures and not experiencing the rampant side effects some claim will occur without the benefit of these techniques and protocols. Maybe I'm being too simplistic in my thinking, but it seems to me that being respectful of the patient's comfort and ability to tolerate a particular jaw posture and ensuring the appliance is balanced and fitting properly is all that is required to avoid the rampant, earth shattering side effects that are forecasted to happen unless a certain technique or protocol is used. Once again, research is required to establish Evidenced Based literature regarding the use of these techniques and protocols. The number of varying bite registration techniques discussed is actually quite remarkable. Some, resulting in the mandible being in a similar position and others in a quite different position; yet all professing to work well. However, the only Evidenced Based approach is that of mandibular advancement. Notwithstanding this, we have clinicians opening vertical, using jaw positions that result from making specific sounds and others based on muscular balance and yet others based on the most comfortable vertical and protrusive position etc. This begs the following question; how can moving the mandible to all these different positions result in a similar and acceptable outcome? There is no evidence that any particular technique works better than another. And although it is difficult to understand how some of these approaches work, it is equally difficult to imagine that educated clinicians would continue to use and stand by a particular protocol that does not work. In the end, their efforts have to pass the "Polysomnography" test! Just sayn So, in the absence of any evidence to the contrary, I have to accept that they all seem to work. Leading to the following conclusion: It seems to be more about moving the jaw, rather than where you move the jaw. Having said this, I think it is important to emphasis that the only Evidenced Based Literature support is for mandibular advancement. Furthermore, the literature suggests that Excessive Vertical Opening can be detrimental to airway patency. Ultimately, all of the starting jaw positions that were discussed strive to establish a jaw posture that the patient can comfortably tolerate and adjustments are made from there, to other jaw postures that the patient can comfortably tolerate. Barry Glassman said it very well, "There is no relationship between the laxity of the collateral ligaments, the eminence angles and the state of the stylomandibular ligaments (those factors that control protrusion) and the effect on the pharyngeal musculature during sleep". In fact, one does not really know what position is the best starting position and basing it on a percentage of the jaw's range of motion simply defies logic. Consider the following: Matrix identifies responders at all levels of protrusion Other Bite Techniques result in responders at varied levels of protrusion and vertical opening A comparison of outcomes using appliances constructed using the Phonetic Bite to appliances constructed using Usual and Customary Jaw Advancement, results in "No Statistically Significant Difference" in the patient's response to treatment. Even though the patient's ended up in a very different jaw position. It seems to me that there is plenty of anecdotal evidence to suggest that Kent Smith is correct. Quoting Kent for a second time, "Hey, it's all a guess anyway!" Whichever technique is used, it appears to involve repositioning of the mandible and then further repositioning until both "subjective symptom" and "objective AHI" resolution occurs. The exception to this is the Evidence Based tools and associated protocols that have been developed that allow us to evaluate the impact of varying Jaw position during sleep; the Apnea Guard and the MATRx. Both of these are discussed in some detail and both show much promise in helping us to establish responders and also the optimum jaw position. We are in dire need of more good research on the possible benefits of varying Vertical and use a particular Jaw Postures, such as that derived by the Phonetic bite that results in much less protrusion. The similarity in outcomes in the retrospective study on Phonetic vs. Advancement Bites suggests that an increase in Vertical may in fact be a surrogate for jaw advancement. Todd Morgan has developed a protocol to use along with the Apnea Guard that helps to account for variance of vertical based on patient phenotype, something he has developed from observations in his previous research. Of course, if this phenotyping is further confirmed in the literature, I am sure that this same feature could be added to the MATRx system. Very exciting times for Sleep Disorders Dentistry. Considering all of the potential distractions a clinician new to this field is exposed to, I think Barry Glassman provides some very solid advice, "Long ago I learned that making as good a diagnosis as possible (with some degree of reality) – and taking the approach of doing the least we have to do to help our patients, taking the time to listen to their concerns and goals… " is all that is needed, no more and no less. This turned out to be a very lengthy and at times quite heated discussion, I would never of expected this for a discussion on establishing a starting point for a sleep apnea appliance! The passion that these clinicians practice with is to be commended. I am truly appreciative of all that participated and sincerely hope that this summary consensus will be helpful to clinicians new to this field and perhaps thought provoking to those of us that have been at it a while. I look forward to further discussions on the SleepDisordersDentistry LinkedIn Group. John Viviano DDS D ABDSM  SleepDisordersDentistry.com  SleepDisordersDentistry LinkedIn Group Read More » 19th Surgical Research Days. Section of Surgical Research of the German Society of Surgery. October 8-10, 2015, Würzburg, Germany: Abstracts Eur Surg Res 2015;55:198-289 Read More » ESSR News Eur Surg Res 2015;55:290 Read More » The impact of perioperative dexamethasone on swallowing impairment score after thyroidectomy. A retrospective study of 118 total thyroidectomies Abstract Even though more than half of patients undergoing thyroidectomy complain of non-specific swallowing symptoms, when no laryngeal nerve injury is involved the importance of these complications is often overlooked. The impact of steroids on swallowing symptoms after thyroidectomy has never been evaluated so far. In our study swallowing impairment score 48-hours after total thyroidectomy was significant higher than preoperative, but no significant difference was noticed between preoperative and 1-month after surgery scores. Our results showed that swallowing impairment score 48 hours after total thyroidectomy was significant lower in patients who received perioperative dexamethasone. Patients may benefit from the use of a single perioperative dose of dexamethasone, since it may significantly reduce early post-thyroidectomy swallowing symptoms. This article is protected by copyright. All rights reserved. Read More » Awake Flexible Fiberoptic Laryngoscopy to diagnose glossoptosis in Robin Sequence patients Abstract Background Robin Sequence (RS) is usually defined as the combination of micrognathia, glossoptosis and upper airway obstruction. No objective criteria to diagnose RS exist. To compare management strategy results, a single RS definition using objective criteria is needed. The most frequently used primary diagnostic tool for glossoptosis is awake Flexible Fiberoptic Laryngoscopy (aFFL). Objectives To determine the reliability of the aFFL videos as an independent diagnostic tool itself, rather than on the complete evaluation of a patient. Design, setting, participants All RS individuals from an existing cohort with an available aFFL video were included retrospectively. Thirty age-matched patients without pathologic findings on aFFL were used as controls. aFFL videos were scored by six otolaryngologists as: a. Marked glossoptosis, b. Mild glossoptosis, c. Severity unknown, d. No glossoptosis, e. Insufficient video quality. Videos were anonymized and rated twice, in altered sequences, after a washout period of minimally 2 weeks. Main outcome measures Inter-rater and intra-rater agreement. Results 26 videos of 16 RS patients and 30 videos of controls were included. Inter-rater agreement was fair in the whole group (κ: 0.320) and RS group (κ: 0.226), and fair to moderate in determining presence of glossoptosis (total group κ: 0.430; RS κ: 0.302; controls κ: 0.212). The intra-rater agreement for presence of glossoptosis in RS was moderate (κ: 0.541). Conclusions aFFL offers fair to moderate inter-rater agreement, with moderate intra–rater agreement, in evaluating glossoptosis in RS. Using aFFL as the single tool in choosing management strategies in RS seems insufficient. There is need for a more reliable, patient friendly diagnostic tool or an internationally accepted aFFL scoring system, to diagnose glossoptosis in RS. This article is protected by copyright. All rights reserved. Read More » Synchronous Fibrolamellar Hepatocellular Carcinoma and Auricular Myxoma Synchronic occurrence of benign and malignant tumors is extremely rare. Fibrolamellar hepatocellular carcinoma represents 1% to 2% of all hepatocarcinomas, while myxomas represent about half of all the cases of primary tumors of the heart. We present the case of a 53-year-old woman with a left atrial myxoma that was surgically removed. Several weeks later, the patient returned to the hospital with abdominal pain. CT scan showed a mass in the left lobe of the liver that was resected and diagnosed as fibrolamellar hepatocellular carcinoma. As of this writing, the patient is healthy. Read More » Standardization of Free T4 and Harmonization of TSH Measurements: A Request for Input from Endocrinologists and Other Physicians Eur Thyroid J Read More » Clinical outcomes with transoral robotic surgery for supraglottic squamous cell carcinoma: Experience of a French evaluation cooperative subgroup of GETTEC Abstract Background Transoral, minimally invasive, organ preservation surgeries are increasingly used to treat laryngopharyngeal carcinomas to avoid the toxicity associated with combined chemoradiotherapy (CRT) regimens. This study investigated the efficiency, safety, and functional outcomes of using transoral robotic surgery (TORS) to perform supraglottic laryngectomy (SGL). Methods This was a multicenter study using a case series with planned data collection from 2009 to 2012 for patients with supraglottic squamous cell carcinomas (SCCs) who underwent an SGL using TORS. Results Eighty-four of the 262 patients underwent TORS for a supraglottic SCC. Within 24 hours of surgery, 24% of the patients began an oral diet. The median use of a feeding tube was 8 days for 76% of other patients. Definitive percutaneous gastrostomy feeding was necessary for 9.5% of the patients. Twenty-four percent of the patients did require a tracheostomy, and the median use was 8 days. One percent of the patients had a definitive tracheostomy. Aspiration pneumonia was observed in 23% of the patients during the postoperative course, and was responsible for the death of 1 patient. Postoperative bleeding occurred in 18% of the patients. Based on the pathology results, 51% of the patients received adjuvant radiation therapy. Conclusion TORS for SGL, in the intermediate stage of SCC, provides a safe procedure with good functional outcomes and fast recovery times; however, adverse events are possible. Consequently, this technique requires good selection criteria for the patients to reduce the risk of postoperative complications. © 2015 Wiley Periodicals, Inc. Head Neck, 2015 Read More » A population-based analysis of Head and Neck hemangiopericytoma Objectives/Hypothesis Hemangiopericytomas (HPC) are tumors that arise from pericytes. Hemangiopericytomas of the head and neck are rare and occur both extracranially and intracranially. This study analyzes the demographic, clinicopathologic, treatment modalities, and survival characteristics of extracranial head and neck hemangiopericytomas (HN-HPC) and compares them to HPCs at other body sites (Other-HPC). Methods The Surveillance, Epidemiology, and End Results (SEER) database (1973–2012) was queried for HN-HPC (121 cases) and Other-HPC (510 cases). Data were analyzed comparatively with respect to various demographic and clinicopathologic factors. Disease-specific survival (DSS) was analyzed using the Kaplan-Meier model. Results There was no significant difference in age at time of diagnosis between HN-HPC and Other-HPC. Head and neck HPC was most commonly located in the connective and soft tissue (18.4%), followed by the nasal cavity and paranasal sinuses (8.5%). Head and neck HPCs were smaller than Other-HPC (P < 0.0001) and more likely to be a lower histologic grade (P < 0.0097). The primary treatment modality for HN-HPC was surgery alone, used in 55.8% of cases. The 5-, 10-, and 20-year DSS for HN-HPC were 84.0%, 79.4%, and 69.4%, respectfully. Higher histologic grade and the presence of distant metastases were poor prognostic factors for HN-HPC. Conclusion Head and neck HPCs are rare tumors. This study represents the largest series of HN-HPCs to date. Surgery alone is the primary treatment modality for HN-HPC, with a favorable prognosis. Adjuvant radiotherapy does not appear to confer a survival benefit for any body site. Level of Evidence 4. Laryngoscope, 2015 Read More » Histopathological features of sinonasal inverted papillomas in chinese patients Objectives/Hypothesis Nasal inverted papilloma (IP) is a benign tumor with high recurrence rates. Evidence of inflammation has been reported in IP in Caucasian studies. This study aimed to investigate the histopathological patterns and their associations with clinical characteristics in Chinese patients with IP. Study Design Basic science study. Methods IP tissues were obtained from 50 Chinese patients with unilateral IPs. Biopsies of inferior turbinate mucosa from 17 healthy subjects were used as controls. The histological patterns and severity of epithelial remodeling and inflammatory cell infiltration were evaluated and analyzed for associations with clinical characteristics. Results Thirty-one percent of IP specimens were classified as grade I (mild remodeling) and 49% as grade II (moderate and severe remodeling). Concomitant inflammatory nasal polyps were found in 14 patients (28%). Recurrent IP was strongly associated with grade II (odds ratio: 5.81, 95% confidence interval: 1.34-25.18). Except CD4+ T cells, quantities of neutrophils, macrophages, eosinophils, CD8+ T cells, and FoxP3+ T-reg cells were significantly elevated in IP. Of these, neutrophils were the predominant cell type in IP. Conclusions Inflammation may have potential roles in IPs and the higher grade of epithelial remodeling was associated with the recurrence of IPs. Level of Evidence NA Laryngoscope, 2015 Read More » Endoscopic endonasal greater palatine artery cauterization at the incisive foramen for control of anterior epistaxis Objectives/Hypothesis To describe the anatomy of the incisive foramen and the transnasal endoscopic approach to the greater palatine artery at this foramen, and to evaluate the importance of the greater palatine artery as a cause of recurrent anterior epistaxis. Study Design Anatomical dissection, radiographic study, and prospective case series. Setting Academic Medical Center. Methods Sixty-nine computed tomography scans were reviewed, and measurements were made of the incisive foramina's distance to the anterior nasal spine and subnasale. Twenty-two cadavers had sagittal split craniotomies performed prior to the measurements. The distance from the anterior nasal spine to the incisive foramen was documented. We also present an illustrative case series of patients who underwent endoscopic cautery of the greater palatine artery at the incisive foramen. Results Radiographic review of the incisive foramen revealed a mean anterior nasal spine to incisive foramen distance on the right and left of 7.9 and 8.1 mm, respectively. The mean distance from the subnasale to incisive foramen on the right and left were 24.7 and 24.9 mm, respectively. Conclusions Endoscopic cauterization of the greater palatine artery at the incisive foramen is a safe and effective method to control recurrent anterior epistaxis. The incisive foramen can be predictively found within 1 cm of the anterior nasal spine. Our case series corroborates the above. Level of Evidence 4. Laryngoscope, 2015 Read More » Castleman's Disease Presenting as a Parotid Mass in the Pediatric Population: A Report of 2 Cases Introduction. Angiofollicular lymph node hyperplasia (Castleman's disease) is a nonmalignant lymphoproliferative disorder that generally involves the lymph nodes of young adults, most commonly in the mediastinum. Rarely, Castleman's disease may present in the parotid gland. The disease can be further classified into unicentric or multicentric forms, with considerable differences in presentation, treatment, and prognosis. Case(s). We present cases of two pediatric patients, aged 7 and 11, who both presented with a slow-growing, painless parotid mass. In each case, the mass was excised via a superficial parotidectomy and the diagnosis made postoperatively upon further pathologic examination. At 6 months of follow-up, both had fully intact facial nerve function and no evidence of recurrence. Discussion. Castleman's disease presents a diagnostic challenge in the head and neck region, as radiographic characteristics and fine needle aspiration results are often inconclusive. Definitive diagnosis requires surgical excision for pathologic examination. The unicentric form generally presents as a painless mass and can be successfully treated with complete excision. The multicentric form is associated with constitutional symptoms and its treatment remains controversial. Conclusion. Although rare, clinicians should be aware of both forms of Castleman's disease when creating a differential diagnosis for parotid masses. Read More » Cystadenocarcinoma of the salivary glands with potential lymph node metastasis Publication date: Available online 4 October 2015 Source:Auris Nasus Larynx Author(s): Takashi Mukaigawa, Ryuichi Hayashi, Masakazu Miyazaki, Takeshi Shinozaki, Toshifumi Tomioka, Satoshi Fujii Cystadenocarcinoma derived from the salivary gland in the head and neck region is an extremely rare malignancy. Therefore, the clinicopathological characteristics is not well understood. The purpose of this study was to clarify the clinicopathological characteristics, and present a total of four patients who were treated at the National Cancer Center Hospital East during the period between 1995 and 2012. The patients were all male, with ages ranging from 47 to 74 years old. The primary sites were the parotid glands, submandibular gland and minor salivary gland of the tongue. Within the follow-up period from 19 to 54 months, lymph node metastases were observed in three of the four patients. However, all the patients were salvaged by additional resection, including neck dissection, and remain alive to date without distant metastases. Cystadenocarcinoma is classified as a low-grade histological subtype of salivary gland tumors. Although the tumor has the potential to produce lymph node metastases, as shown in our patients, it is generally an indolent tumor with a good prognosis as compared with high-grade subtypes. This study suggests that a long-term follow up paying close attention to lymph node metastases is necessary for cystadenocarcinoma. Read More » Posttraumatic olfactory dysfunction Publication date: Available online 4 October 2015 Source:Auris Nasus Larynx Author(s): Daniel H. Coelho, Richard M. Costanzo Impairment of smell may occur following injury to any portion of the olfactory tract, from nasal cavity to brain. A thorough understanding of the anatomy and pathophysiology combined with comprehensively obtained history, physical exam, olfactory testing, and neuroimaging may help to identify the mechanism of dysfunction and suggest possible treatments. Although most olfactory deficits are neuronal mediated and therefore currently unable to be corrected, promising technology may provide novel treatment options for those most affected. Until that day, patient counseling with compensatory strategies and reassurance is essential for the maintenance of safety and QoL in this unique and challenging patient population. Read More » Past, present and future of macrolide therapy for chronic rhinosinusitis in Japan Publication date: Available online 4 October 2015 Source:Auris Nasus Larynx Author(s): Takeshi Shimizu, Harumi Suzaki In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review. Read More » Predictive factors and pattern of central lymph node metastasis in unilateral papillary thyroid carcinoma Publication date: Available online 3 October 2015 Source:Auris Nasus Larynx Author(s): Yong Bae Ji, Han Seok Yoo, Chang Myeon Song, Chul Won Park, Chang Beom Lee, Kyung Tae ObjectiveProphylactic central neck dissection (CND) for papillary thyroid carcinoma (PTC) remains controversial. The aim of this study was to evaluate the patterns and predictive factors of central lymph node metastasis in cases of PTC that were clinically determined to be node negative.MethodsWe studied 485 patients who have unilateral PTC without clinical lymph node metastasis and underwent total thyroidectomy and prophylactic bilateral CND from 2003 to 2012, retrospectively. The frequency, subsite and predictive factors of central lymph node metastasis were analyzed.ResultsIn total, 166 (32.4%) patients had occult central lymph node metastases. The most common subsite of central node metastases was the ipsilateral paratracheal lymph node (26.0%), followed by pretracheal (12.5%), prelaryngeal (5.0%), and contralateral paratracheal (3.9%) lymph nodes. The tumor size larger than 0.5cm (p=0.003), age under 45 (p<0.001) and extrathyroidal extension (p=0.028) were associated with ipsilateral central compartment metastasis in multivariate analysis. Contralateral central node metastasis was associated with tumor size >3cm, age under 45, and multifocality and ipsilateral central node metastasis in univariate analysis, but it was associated with only ipsilateral central node metastasis in multivariate analysis (p=0.001).ConclusionProphylactic CND might be considered for PTC patients with large tumor size or extrathyroidal extension based on rates of lymph node metastasis. Unilateral CND might be appropriate as prophylactic CND due to the low metastatic rate to the contralateral paratracheal node. Read More » Castleman's Disease Presenting as a Parotid Mass in the Pediatric Population: A Report of 2 Cases Introduction. Angiofollicular lymph node hyperplasia (Castleman's disease) is a nonmalignant lymphoproliferative disorder that generally involves the lymph nodes of young adults, most commonly in the mediastinum. Rarely, Castleman's disease may present in the parotid gland. The disease can be further classified into unicentric or multicentric forms, with considerable differences in presentation, treatment, and prognosis. Case(s). We present cases of two pediatric patients, aged 7 and 11, who both presented with a slow-growing, painless parotid mass. In each case, the mass was excised via a superficial parotidectomy and the diagnosis made postoperatively upon further pathologic examination. At 6 months of follow-up, both had fully intact facial nerve function and no evidence of recurrence. Discussion. Castleman's disease presents a diagnostic challenge in the head and neck region, as radiographic characteristics and fine needle aspiration results are often inconclusive. Definitive diagnosis requires surgical excision for pathologic examination. The unicentric form generally presents as a painless mass and can be successfully treated with complete excision. The multicentric form is associated with constitutional symptoms and its treatment remains controversial. Conclusion. Although rare, clinicians should be aware of both forms of Castleman's disease when creating a differential diagnosis for parotid masses. Read More » Copy number increase of oncoprotein CIP2A is associated with poor patient survival in human head and neck squamous cell carcinoma Background CIP2A, an inhibitor of PP2A tumour suppressor function, is a widely overexpressed biomarker of aggressive disease and poor therapy response in multiple human cancer types. Methods CIP2A and DPPA4 copy number alterations and expression were analysed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in different cell lines and a tissue microarray of 52 HNSCC patients. Results were correlated with patient survival and other clinicopathological data. Results CIP2A and DPPA4 copy number increase occurred at a relatively high frequency in human HNSCC patient samples. CIP2A but not DPPA4 FISH status was significantly associated with patient survival. CIP2A detection by combining IHC with FISH yielded superior resolution in the prognostication of HNSCC. Conclusions CIP2A copy number increase is associated with poor patient survival in human HNSCC. We suggest that the reliability and prognostic value of CIP2A detection can be improved by performing FISH analysis to CIP2A IHC positive tumours. Read More » Marked lateral deviation of the phrenic nerve due to variant origin and course of the thyrocervical trunk: a cadaveric study Abstract Phrenic nerve impairment can often lead to serious respiratory disorders under various pathological conditions. During routine dissection of an 88-year-old Japanese male cadaver, a victim of heart failure, we recognized an extremely rare variation of the right thyrocervical trunk arising from the subclavian artery laterally to the anterior scalene muscle. In addition to that, the ipsilateral phrenic nerve was drawn and displaced remarkably laterad by this vessel. We examined all of the branches arising from subclavian arteries, phrenic nerves and diaphragm muscles. The embryological background of this arterial variation is considered. The marked displacement with prolonged strain had a potential to cause phrenic nerve impairment with an atrophic change of the diaphragm muscle. Recently many image diagnostic technologies have been developed and are often used. However, it is still possible that rare variations like this case may be overlooked and can only be recognized by intimate regional examination while keeping these rare variations in mind. Read More » The impact of transoral robotic surgery on the overall treatment of oropharyngeal cancer patients Objectives/Hypothesis To assess adjuvant therapy in patients undergoing surgical management of oropharyngeal squamous cell carcinoma (OPSCCA) with transoral robotic surgery (TORS) and neck dissection. Study Design A prospective, nonrandomized, consecutive patient series from two separate protocols in a tertiary academic medical center. Methods Patients undergoing treatment for OPSCCA were selected from a prospective protocol evaluating functional and oncologic outcomes following TORS with a comparator group of OPSCCA patients receiving definitive chemoradiotherapy (CRT) participating in a separate prospective protocol. Results Forty-two patients represented the TORS group and 38 the CRT group. Twenty (48%) of the TORS patients received surgery only, whereas nine (21%) underwent adjuvant radiotherapy and 13 (31%) adjuvant CRT. Adjuvant therapy patients had a higher overall T (P =.0007) and N (P < .0001) stage than the TORS-only group. Surgery resulted in stage changes in 18 (43%) patients, leading to alteration in therapy for nine (21%) patients. The 3-year overall survival (OS), disease-specific survival (DSS), and locoregional control was 74% versus 90% (P = .30), 94% versus 94% (P = .91), and 72% versus 91% (P = .19) for the TORS-alone versus TORS plus adjuvant therapy groups, respectively. Comparison with the CRT group revealed a survival benefit in the TORS group approaching significance, with a 3-year OS of 83% versus 57% (P = .06) and DSS of 94% versus 85% (P = .08), respectively. Conclusions Primary surgical management of OPSCCA with TORS and neck dissection provides accurate staging information, which can lead to the appropriate selection of subsequent therapy. This approach does not compromise survival and warrants additional investigation. Level of Evidence 3b. Laryngoscope, 2015 Read More » Identification of checkpoints in human T-cell development using severe combined immunodeficiency stem cells Publication date: Available online 4 October 2015 Source:Journal of Allergy and Clinical Immunology Author(s): Anna-Sophia Wiekmeijer, Karin Pike-Overzet, Hanna IJspeert, Martijn H. Brugman, Ingrid L.M. Wolvers-Tettero, Arjan C. Lankester, Robbert G.M. Bredius, Jacques J.M. van Dongen, Willem E. Fibbe, Anton W. Langerak, Mirjam van der Burg, Frank J.T. Staal BackgroundSevere combined immunodeficiency (SCID) represents congenital disorders characterized by a deficiency of T cells caused by arrested development in the thymus. Yet the nature of these developmental blocks has remained elusive because of the difficulty of taking thymic biopsy specimens from affected children.ObjectiveWe sought to identify the stages of arrest in human T-cell development caused by various major types of SCID.MethodsWe performed transplantation of SCID CD34+ bone marrow stem/progenitor cells into an optimized NSG xenograft mouse model, followed by detailed phenotypic and molecular characterization using flow cytometry, immunoglobulin and T-cell receptor spectratyping, and deep sequencing of immunoglobulin heavy chain (IGH) and T-cell receptor δ (TRD) loci.ResultsArrests in T-cell development caused by mutations in IL-7 receptor α (IL7RA) and IL-2 receptor γ (IL2RG) were observed at the most immature thymocytes much earlier than expected based on gene expression profiling of human thymocyte subsets and studies with corresponding mouse mutants. T-cell receptor rearrangements were functionally required at the CD4−CD8−CD7+CD5+ stage given the developmental block and extent of rearrangements in mice transplanted with Artemis-SCID cells. The xenograft model used is not informative for adenosine deaminase–SCID, whereas hypomorphic mutations lead to less severe arrests in development.ConclusionTransplanting CD34+ stem cells from patients with SCID into a xenograft mouse model provides previously unattainable insight into human T-cell development and functionally identifies the arrest in thymic development caused by several SCID mutations. Read More » Clinical characteristics and genotype-phenotype correlations in C3 deficiency Publication date: Available online 4 October 2015 Source:Journal of Allergy and Clinical Immunology Author(s): Yuka Okura, Ichiro Kobayashi, Masafumi Yamada, Satoshi Sasaki, Yutaka Yamada, Ichiro Kamioka, Rie Kanai, Yutaka Takahashi, Tadashi Ariga Read More » Protein disulfide isomerase–endoplasmic reticulum resident protein 57 regulates allergen-induced airways inflammation, fibrosis, and hyperresponsiveness Publication date: Available online 4 October 2015 Source:Journal of Allergy and Clinical Immunology Author(s): Sidra M. Hoffman, David G. Chapman, Karolyn G. Lahue, Jonathon M. Cahoon, Gurkiranjit K. Rattu, Nirav Daphtary, Minara Aliyeva, Karen A. Fortner, Serpil C. Erzurum, Suzy A.A. Comhair, Prescott G. Woodruff, Nirav Bhakta, Anne E. Dixon, Charles G. Irvin, Yvonne M.W. Janssen-Heininger, Matthew E. Poynter, Vikas Anathy BackgroundEvidence for association between asthma and the unfolded protein response is emerging. Endoplasmic reticulum resident protein 57 (ERp57) is an endoplasmic reticulum–localized redox chaperone involved in folding and secretion of glycoproteins. We have previously demonstrated that ERp57 is upregulated in allergen-challenged human and murine lung epithelial cells. However, the role of ERp57 in asthma pathophysiology is unknown.ObjectivesHere we sought to examine the contribution of airway epithelium–specific ERp57 in the pathogenesis of allergic asthma.MethodsWe examined the expression of ERp57 in human asthmatic airway epithelium and used murine models of allergic asthma to evaluate the relevance of epithelium-specific ERp57.ResultsLung biopsy specimens from asthmatic and nonasthmatic patients revealed a predominant increase in ERp57 levels in epithelium of asthmatic patients. Deletion of ERp57 resulted in a significant decrease in inflammatory cell counts and airways resistance in a murine model of allergic asthma. Furthermore, we observed that disulfide bridges in eotaxin, epidermal growth factor, and periostin were also decreased in the lungs of house dust mite–challenged ERp57-deleted mice. Fibrotic markers, such as collagen and α smooth muscle actin, were also significantly decreased in the lungs of ERp57-deleted mice. Furthermore, adaptive immune responses were dispensable for house dust mite–induced endoplasmic reticulum stress and airways fibrosis.ConclusionsHere we show that ERp57 levels are increased in the airway epithelium of asthmatic patients and in mice with allergic airways disease. The ERp57 level increase is associated with redox modification of proinflammatory, apoptotic, and fibrotic mediators and contributes to airways hyperresponsiveness. The strategies to inhibit ERp57 specifically within the airways epithelium might provide an opportunity to alleviate the allergic asthma phenotype. Read More » Prevalence of primary headache disorders in Fayoum Governorate, Egypt Background: There is abundance of epidemiological studies of headache in developed and western countries; however, data in developing countries and in Egypt are still lacking. This study aims to detect the prevalence of primary headache disorders in both urban and rural sectors in Fayoum governorate, Egypt. Methods: A total of 2600 subjects were included using multi-stage stratified systematic random sampling, with respondent rate of 91.3 %. A pre-designed Arabic version, interviewer-administered, pilot tested structured questionnaire was developed according to The International Classification of Headache Disorders, 3rd edition (beta version), and this questionnaire was validated and the strength of agreement in headache diagnosis was good. Results: The 1-year headache prevalence was 51.4 %, which was more prevalent in urban dwellers. The most common primary headache type was episodic tension type headache (prevalence; 24.5 %), followed by episodic migraine (prevalence; 17.3 %), both types peaked in midlife. Headache disorders were more common in females with exception of cluster headache that showed the expected male dominance. The risk of chronic headache increased more than one fold and half when the participants were females, married, and in those with high education. More than 60 % of our participants did not seek medical advice for their headaches problem; this percentage was higher in rural areas. Conclusions: Primary headache disorders are common in Egypt; prevalence rate was comparable with western countries with exception of episodic tension headache. Still headache is under-estimated and under-recognized in Egypt and this problem should be targeted by health care providers. Read More » Elevated blood pressure and headache disorders in China – associations, under-treatment and implications for public health Background: Both hypertension (HTN) and headache disorders are highly prevalent worldwide. Our purpose, in a nationwide study of the Chinese general population, was to evaluate any association between primary headache disorders and elevated blood pressure (eBP). We could not collect data on antihypertensive therapy, but took the view that, whatever such therapy might be taken, eBP was a sign that it was failing to meet treatment needs. Therefore, as a secondary purpose, important from the public-health perspective, we would present the prevalence of eBP (treated or not) as indicative of unmet health-care need in China. Methods: This was a questionnaire-based nationwide cross-sectional door-to-door survey using cluster random-sampling, selecting one adult (18–65 years) per household. Headache was diagnosed by ICHD-II criteria and eBP as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. Chi-squared test and multivariate logistic regression analysis were used to assess the strength and significance of associations. We set significance at P ≤ 0.05. Results: Of 5,041 survey participants (participation rate 94.1 %), 154 were excluded because of missing BP data, leaving 4,987 for analysis [mean age: 43.6 ± 12.8 years; male 2,532 (mean age: 43.4 ± 12.9 years); female 2,455 (mean age 43.9 ± 12.8 years)]. There were 466 participants with migraine, 535 with tension type headache (TTH) and 48 with all causes of headache on ≥15 days/month. The prevalence of eBP was 22.1 % (males 22.9 %, females 21.3 %). No associations of eBP with any of the headache disorders survived multivariate adjusted analysis. The demographic and anthropometric variables most strongly associated with eBP were higher age (AOR 3.7) and being overweight (AOR 2.4), seen in both genders. Less strong were male gender, lower educational level and urban habitation. Conclusions: We found no clear-cut associations between eBP and any headache disorder. The associations with demographic and anthropometric variables may have acted as confounders in past reports to the contrary. We did find an alarmingly high prevalence of eBP, recognizing that this signals substantial under-treatment in China of a serious condition, and therefore a major public-health concern. Read More » The Effects of Visual Stimuli on the Spoken Narrative Performance of School-Age African American Children Purpose This study investigated the fictional narrative performance of school-age African American children across 3 elicitation contexts that differed in the type of visual stimulus presented. Method A total of 54 children in Grades 2 through 5 produced narratives across 3 different visual conditions: no visual, picture sequence, and single picture. Narratives were examined for visual condition differences in expressive elaboration rate, number of different word roots (NDW) rate, mean length of utterance in words, and dialect density. The relationship between diagnostic risk for language impairment and narrative variables was explored. Results Expressive elaboration rate and mean length of utterance in words were higher in the no-visual condition than in either the picture-sequence or the single-picture conditions. NDW rate was higher in the no-visual and picture-sequence conditions than in the single-picture condition. Dialect density performance across visual context depended on the child's grade, so that younger children produced a higher rate of African American English in the no-visual condition than did older children. Diagnostic risk was related to NDW rate and dialect density measure. Conclusion The results suggest the need for narrative elicitation contexts that include verbal as well as visual tasks to fully describe the narrative performance of school-age African American children with typical development. Read More » Polysomnographic Findings after Adenotonsillectomy for Obstructive Sleep Apnea in Obese and Non-Obese Children: A Systemic review and Meta-Analysis Abstract Background Use of polysomnography (PSG) is the gold standard of diagnosis and measurement of treatment effectiveness for pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy (T&A) is effective in diminishing the apnea-hypopnea index (AHI), a meta-analysis of post-operative changes for all other PSG parameters, and outcome comparisons between obese and non-obese children following T&A, have never been conducted. Objective of review To comprehensively review polysomnographic findings after surgery for obese and non-obese children with OSA. Search Strategy Study protocol was registered on PROSPERO (CRD42013004737). Two authors independently searched databases including PubMed, MEDLINE, EMBASE, and Cochrane Review from January 1997 to July 2014. The keywords used included: sleep apnea, OSA, sleep apnea syndromes, tonsillectomy, adenoidectomy, infant, child, adolescent and Humans. Evaluation method A comprehensive systemic review and meta-analysis for literature for OSA children treated by T&A with polysomnography data. Random effects model was applied to determine postoperative sleep parameter changes and the surgical success rate between obese and non-obese groups. The quality of studies was assessed using the Newcastle-Ottawa Scale. Results In total, 51 studies with 3413 subjects were enrolled. After surgery, sleep architecture was altered by a significant decrease in sleep stage 1, and an increase in slow wave sleep and the rapid eye movement stage, and enhanced sleep efficiency. The mean difference between pre- and post-operative was a significant reduction of 12.4 event/hour in AHI, along with a reduction of obstructive index, hypopnea index, central index, and arousal index. Mean and minimum oxygen saturation increased significantly after surgery. The overall success rate was 51% for postoperative AHI <1 (obese vs. non-obese vs. combined, 34% vs. 49% vs. 56%), and 81% for AHI <5 (obese vs. non-obese vs. combined, 61% vs. 87% vs. 84%). Meta-regression analyses demonstrate that postoperative AHI was positively correlated with AHI and body mass index z score before surgery. Conclusions Meta-analysis of current literature shows T&A offers prominent improvement in a variety of sleep parameters. Improvements in non-obese children exceeded those for obese children. Postoperative residual OSA remained in roughly half of the children, especially those with severe disease and obesity, making additional treatment strategies and/or long-term follow-up highly desirable. This article is protected by copyright. All rights reserved. Read More » The Role of Pectoralis Major Flap in Reducing the Incidence of Pharyngocutaneous Fistula Following Total Laryngectomy; A single center experience with 102 patients Abstract Pharyngocutaneous fistula following total laryngectomy is a serious complication. This retrospective analysis from a university-affiliated tertiary care medical center presents our experience with 102 total laryngectomy patients. 59 patients underwent salvage laryngectomy and the remaining 43 patients underwent primary laryngectomy. The only factors found to be associated with increases risk for the development of pharyngocutaneous fistula were prior radiotherapy or chemoradiotherapy. Pectoralis Major flap did not reduce the risk for the development of a pharyngocutaneous fistula following total laryngectomy nor reduced its severity. This article is protected by copyright. All rights reserved. Read More » Recruitment, response rates and characteristics of 5511 people enrolled in a prospective clinical cohort study: head and neck 5000 Abstract Head and neck cancer is an important cause of ill health with rapidly changing aetiology. Survival appears to have improved but the reasons for this are unclear. Adequately-powered, longitudinal studies in people with head and neck cancer are required. We recruited 5511 people with head and neck cancer to a large DNA-backed clinical cohort. Multi-centre clinical cohort studies in head and neck cancer are feasible in the UK. This article is protected by copyright. All rights reserved. Read More » Distinct modulation of allergic T cell responses by subcutaneous versus sublingual allergen-specific immunotherapy Abstract Background Allergen-specific immunotherapy is the only curative treatment for type I allergy. It can be administered subcutaneously (SCIT) or sublingually (SLIT). The clinical efficacy of these two treatment modalities appears to be similar, but potential differences in the immunological mechanisms involved have not been fully explored. Objective To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). Methods Grass pollen allergic patients were randomized into groups receiving either SCIT injections, or SLIT tablets or neither. PBMC were tested for Timothy grass (TG)-specific cytokine production by ELISPOT after in vitro expansion with TG peptide pools. Phenotypic characterization of cytokine producing cells was performed by FACS. Results In the SCIT group, decreased IL-5 production was observed starting 10 months after treatment was commenced. At 24 months, T cell responses showed IL-5 levels significantly below the before treatment baseline. No significant reduction of IL-5 was observed in the SLIT or untreated group. However, a significant transient increase in IL-10 production after 10 months of treatment compared to baseline was detected in both treatment groups. FACS analysis revealed that IL-10 production was associated with CD4+ T cells that also produced IFNγ, and therefore may be associated with an IL-10-secreting type 1 cell phenotype. Conclusion and clinical relevance The most dominant immunological changes on a cellular level was a decrease in IL-5 in the SCIT group and a significant, transient increase of IL-10 observed after 10 months of treatment in both treated groups. The distinct routes of AIT administration may induce different immune-modulatory mechanisms at the cellular level. This article is protected by copyright. All rights reserved. Read More » Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly Abstract Background Asthma in the elderly (aged ≥65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. Objective We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. Methods A total of 249 elderly asthma patients and 98 controls were analyzed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles, and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. Results At baseline, serum SE-IgE concentrations were significantly higher in asthma patients than controls (median 0.16 [IQR 0.04-0.53] vs. 0.10 [0.01-0.19], p<0.001). Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of co-variables (SE-IgE-high [≥0.35 kU/L] vs. negative [<0.10 kU/L] group: OR 7.47, 95% CI 1.86–30.03, p=0.005). Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. Conclusion and Clinical Relevance This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma, and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly. This article is protected by copyright. All rights reserved. Read More » The activity of 11β-hydroxysteroid dehydrogenase type 2 enzyme and cortisol secretion in patients with adrenal incidentalomas Abstract In adrenal incidentaloma (AI) patients, beside the cortisol secretion, a different 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) activity, measurable by 24-h urinary cortisol/cortisone ratio (R-UFF/UFE) (the higher R-UFF/UFE the lower HSD11B2 activity), could influence the occurrence of the subclinical hypercortisolism (SH)-related complications (hypertension, type 2 diabetes, obesity). We evaluated whether in AI patients, UFF levels are associated to UFE levels, and the HSD11B2 activity to the complications presence. In 156 AI patients (93F, age 65.2 ± 9.5 years), the following were measured: serum cortisol after 1 mg-dexamethasone test (1 mg-DST), ACTH, UFF, UFE levels, and R-UFF/UFE (by liquid chromatography–tandem mass spectrometry), the latter was also evaluated in 63 matched-controls. We diagnosed SH (n = 22) in the presence of ≥2 among ACTH <2.2 pmol/L, increased UFF levels, and 1 mg-DST >83 nmol/L. Patients showed higher UFF levels and R-UFF/UFE than controls (75.9 ± 43.1 vs 54.4 ± 22.9 nmol/24 h and 0.26 ± 0.12 vs 0.20 ± 0.07, p < 0.005, respectively) but comparable UFE levels (291 ± 91.1 vs 268 ± 61.5, p = 0.069). The R-UFF/UFE was higher in patients with high (h-UFF, n = 28, 0.41 ± 0.20) than in those with normal (n-UFF, 0.22 ± 0.10, p < 0.005) UFF levels and in patients with SH than in those without SH (0.30 ± 0.12 vs 0.25 ± 0.12, p = 0.04). UFF levels were associated with R-UFF/UFE (r = 0.849, p < 0.001) in n-UFF, but not in h-UFF patients. Among h-UFF patients, the complications prevalence was not associated with R-UFF/UFE values. In AI patients, the UFF increase is not associated with a UFE increase. The HSD11B2 activity is inversely associated with UFF levels in n-UFF patients but not in h-UFF patients, and it is not associated with the SH complications. Read More » Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state? Abstract Myostatin and irisin are two myokines related to energy metabolism, acting on skeletal muscle and recently suggested on adipose tissue in mice. However, the exact role of these myokines in humans has not been fully established. Our aim was to evaluate the relationship between serum levels of myostatin and irisin in type 2 diabetes mellitus patients and non-diabetic controls and to explore its links with metabolic parameters. Case–control study including 73 type 2 diabetes mellitus patients and 55 non-diabetic subjects as control group. Circulating myostatin and irisin levels were measured by enzyme-linked immunosorbent assays. Type 2 diabetes mellitus patients showed significantly lower myostatin levels (p = 0.001) and higher irisin levels (p = 0.036) than controls. An inverse relationship was observed between myostatin and irisin levels (p = 0.002). Moreover, in type 2 diabetes mellitus patients, after adjusting by confounder factors, myostatin was negatively related to fasting plasma glucose (p = 0.005) and to triglyceride levels (p = 0.028) while irisin showed a positive association with these variables (p = 0.017 and p = 0.006 respectively). A linear regression analysis showed that irisin and fasting plasma glucose levels were independently associated to myostatin levels and that myostatin and triglyceride levels were independently associated to irisin concentrations in type 2 diabetes mellitus patients. Our results suggest that serum levels of myostatin and irisin are related in patients with type 2 diabetes. Triglyceride and glucose levels could modulate myostatin and irisin concentrations as a compensatory mechanism to improve the metabolic state in these patients although further studies are needed to elucidate whether the action of these myokines represents an adaptative response. Read More » Statin reduces orbitopathy risk in patients with Graves' disease by modulating apoptosis and autophagy activities Abstract Statins use has been associated with reduced risk for developing orbitopathy among patients with Graves' disease. We hypothesize that statin reduces orbitopathy risk mainly by modulating both apoptosis and autophagy activities in patients with Graves' disease. Read More » Increased thyroid cancer incidence in a basaltic volcanic area is associated with non-anthropogenic pollution and biocontamination Abstract The increased thyroid cancer incidence in volcanic areas suggests an environmental effect of volcanic-originated carcinogens. To address this problem, we evaluated environmental pollution and biocontamination in a volcanic area of Sicily with increased thyroid cancer incidence. Thyroid cancer epidemiology was obtained from the Sicilian Regional Registry for Thyroid Cancer. Twenty-seven trace elements were measured by quadrupole mass spectrometry in the drinking water and lichens (to characterize environmental pollution) and in the urine of residents (to identify biocontamination) in the Mt. Etna volcanic area and in adjacent control areas. Thyroid cancer incidence was 18.5 and 9.6/105 inhabitants in the volcanic and the control areas, respectively. The increase was exclusively due to the papillary histotype. Compared with control areas, in the volcanic area many trace elements were increased in both drinking water and lichens, indicating both water and atmospheric pollution. Differences were greater for water. Additionally, in the urine of the residents of the volcanic area, the average levels of many trace elements were significantly increased, with values higher two-fold or more than in residents of the control area: cadmium (×2.1), mercury (×2.6), manganese (×3.0), palladium (×9.0), thallium (×2.0), uranium (×2.0), vanadium (×8.0), and tungsten (×2.4). Urine concentrations were significantly correlated with values in water but not in lichens. Our findings reveal a complex non-anthropogenic biocontamination with many trace elements in residents of an active volcanic area where thyroid cancer incidence is increased. The possible carcinogenic effect of these chemicals on the thyroid and other tissues cannot be excluded and should be investigated. Read More » Evaluation of safety and efficacy of Dermaveel in treatment of atopic dermatitis Publication date: Available online 3 October 2015 Source:Alergologia Polska - Polish Journal of Allergology Author(s): Aleksandra Wilkowska, Elżbieta Grubska-Suchanek, Roman Nowicki Dermaveel cream, which has been registered for the use in atopic dermatitis (AD), consists of, among others, ectoine and hazel bark extract. To evaluate safety, efficacy and tolerance of the preparation, 242 subjects with AD were included in open-label studies in 64 research sites in Poland. Dermaveel cream was applied to affected skin 2× daily for 4weeks. Patients came for follow-up visits three times – at the beginning of the study and then once every two weeks. Intensity of skin changes was evaluated with the use of SCORAD index and intensity of pruritus and sleep disorders were assessed with the use of analogue scale of 1–10. Reduction of the mean SCORAD index from 42 at visit I to 25 at visit II and to 15 at visit III was observed. Statistically significant reduction of intensity of pruritus and sleep disorders at follow-up visits has also been shown. During the study, patients also evaluated usable properties of the study cream considering ease of spreading, absorption rate, consistency, and smell. Almost all patients assessed these properties as very good or good. On the basis of the conducted study, it has been concluded that Dermaveel cream is a safe and efficient preparation. It can be recommended for use on all parts of the body both in children and adults. Its regular use may reduce the need for topical glucocorticosteroids but it requires further studies. Read More »