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Background Computed tomography (CT) of the paranasal sinuses is the diagnostic reference standard for chronic rhinosinusitis and related inflammatory sinus pathology. Nasal nitric oxide (nNO) levels have been investigated as a diagnostic tool in sinus disease because it decreases with sinus obstruction.Objective The primary aim of the study was to determine the correlation of passive (baseline) and dynamic (humming) nNO to CT findings of sinus inflammation and to sinonasal symptoms measured by the modified Sinonasal Outcome Test (26 items) (SNOT-26).Methods From June 2015 through January 2016, subjects had baseline and humming nNO levels measured with a chemiluminescence NO analyzer, and each subject underwent CT imaging and completed the SNOT-26 survey. CT images were scored using the Lund–Mackay (LM) system (LM scores >3 indicated sinus inflammation). Correlation was measured by linear and ordinal regression analysis that compared SNOT-26 scores, LM scores, and nNO measurements.Results Fourteen subjects were recruited. LM scores had a positive pairwise correlation with total SNOT-26 scores (R2= .1457; correlation = .3817) and nasal-specific SNOT-26 scores (R2= .4036; correlation = .6353). Baseline nasal nNO scores had a negative pairwise correlation with LM scores (R2= .1580; correlation = −.3582), total SNOT-26 scores (R2= .1515; correlation = −.3893), and nasal-specific SNOT-26 scores (R2= .0805; correlation = −.4343). Although baseline nNO levels correlated with LM and SNOT-26 scores, humming nNO levels did not show a similar correlation.Conclusion Baseline passive nNO may be a useful and inexpensive point-of-care screening test for sinonasal opacification.

Chronic cough in interstitial lung disease (ILD) causes significant impairment in quality of life. Effective treatment approaches are needed for cough associated with ILD.

Nocturnal gastroesophageal reflux has been associated with poor sleep quality. Normal physiological adaptations of the aerodigestive system to sleep prolong and intensify nocturnal reflux events. This occurrence leads to sleep disruption, as well as to esophageal, laryngeal, and laryngopharyngeal reflux. Controversy exists on whether OSA and nocturnal reflux are causally linked or merely associated because of shared risk factors. Advances in diagnostic technology have provided new insights into gastroesophageal reflux and the mechanisms of nocturnal reflux during sleep. This update reviews new data on causal links between sleep and gastroesophageal reflux disease.

IMPORTANCE: Refractory chronic cough is a debilitating condition with limited therapeutic options. Laryngeal botulinum toxin type A (BtxA) has been anecdotally reported to benefit patients with chronic cough. We report on our experience with the use of BtxA for the treatment of patients with refractory chronic cough. OBJECTIVE: To describe the effects of electromyography (EMG)-guided thyroarytenoid (TA) BtxA injection for the treatment of refractory chronic cough. DESIGN, SETTING, AND PARTICIPANTS: For this single tertiary referral center retrospective case series, we included all patients with refractory chronic cough who received bilateral EMG-guided TA BtxA injections (n = 22) between July 1, 2013, and July 31, 2014, at the Mayo Clinic in Rochester, Minnesota. INTERVENTION: Bilateral TA BtxA injection. MAIN OUTCOMES AND MEASURES: The primary outcome is a self-reported improvement of 50% or more in cough severity and/or symptoms by a 2-month follow-up telephone call. Adverse events and patient-reported quality measures were also assessed. RESULTS: A total of 22 patients (median [interquartile range] age 61 [57.5-85] years; 19 of 22 women) underwent 31 distinct laryngeal BtxA treatment sessions. The primary outcome of self-reported improvement of 50% or more of cough severity and/or symptoms was achieved in 16 of 31 (52%) treatment sessions. Eleven patients (50%) reported greater than 50% improvement after the first BtxA injection. No major complications occurred. Postprocedural liquid dysphagia had a positive predictive value of 84% and negative predictive value of 100% for response to therapy. CONCLUSIONS AND RELEVANCE: In this case series, laryngeal BtxA injection was well tolerated in patients with refractory chronic cough with half of participants experiencing at least short-term improvement in their cough. The occurrence of liquid dysphagia after a BtxA injection appeared to be predictive of a beneficial response. The durability of response, patient selection criteria, and optimal BtxA dosage remains to be determined.

Acute respiratory worsening (ARW) requiring hospitalization in patients with fibrotic interstitial lung disease (f-ILD) is common. Little is known about the frequency and implications of ARW in IPF and non-IPF ILD patients hospitalized for acute exacerbation (AE) vs known causes of ARW.

Electromyographic evaluation of diaphragmatic neuromuscular disease in patients with COPD is technically difficult and potentially high risk. Defining standard values for diaphragm thickness and thickening ratio using B-mode ultrasound may provide a simpler, safer means of evaluating these patients.

The beneficial effect on renal function achieved by early CNI withdrawal and treatment with everolimus after liver transplantation is still evident after three years.

Cough persisting beyond 8 weeks (ie, chronic cough) is one of the most common reasons for an outpatient visit. A protracted cough can negatively affect one’s quality of life by causing anxiety, physical discomfort, social isolation, and personal embarrassment. Herein, the anatomy and physiology of the cough reflex are reviewed. Upper airway cough syndrome, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease account for most chronic cough after excluding smoking, angiotensin-converting enzyme inhibitor use, and chronic bronchitis. Many patients have more than one reason for chronic cough. Treating the underlying cause(s) resolves cough in most instances. There are some coughs that seem refractory despite an extensive work-up. The possibility of a hypersensitive cough reflex response has been proposed to explain these cases. Several clinical algorithms to evaluate chronic cough are presented.

The long-term safety of patient-administered nebulized lidocaine for control of chronic cough has not been established.

The relationship between asthma controller medication use and exacerbation rates over time is unclear at the population level.

The quality of cold‐stored livers declines with the extension of ischemic time and the risk of primary dys‐ or nonfunction increases. Here, we provide in vivoevidence for the efficacy of the previously developed end‐ischemic gaseous oxygen persufflation technique to resuscitate liver grafts after extended storage times. Porcine livers were recovered according to standard multiorgan procurement protocol. Control livers were cold stored in histidine tryptophan ketoglutarate solution for 10 h (cold storage [CS]; n = 6) at 4°C. In the treatment group (n = 6), livers were additionally subjected to hypothermic reconditioning (HR) by gaseous oxygen persufflation via the caval vein for 2 h before transplantation. Viability was assessed by orthotopic liver transplantation and 1 week follow‐up. HR significantly improved pretransplant energy charge and initial graft function after transplantation. One week survival after CS was 0% whereas five of six pigs (83%) survived in the HR group. At that time, coagulation parameters were in the normal range and histological analysis disclosed healthy liver tissue with normal trabecular architecture in the treated grafts. Molecular analyses identify the prevention of ischemia‐induced decline of cellular autophagy and mitigation of innate immune machinery (high‐mobility group protein B1, interferon‐β) as operative mechanisms among the protective effects provided by HR.

The quality of cold-stored livers declines with the extension of ischemic time and the risk of primary dys- or nonfunction increases. Here, we provide in vivoevidence for the efficacy of the previously developed end-ischemic gaseous oxygen persufflation technique to resuscitate liver grafts after extended storage times. Porcine livers were recovered according to standard multiorgan procurement protocol. Control livers were cold stored in histidine tryptophan ketoglutarate solution for 10 h (cold storage [CS]; n = 6) at 4°C. In the treatment group (n = 6), livers were additionally subjected to hypothermic reconditioning (HR) by gaseous oxygen persufflation via the caval vein for 2 h before transplantation. Viability was assessed by orthotopic liver transplantation and 1 week follow-up. HR significantly improved pretransplant energy charge and initial graft function after transplantation. One week survival after CS was 0% whereas five of six pigs (83%) survived in the HR group. At that time, coagulation parameters were in the normal range and histological analysis disclosed healthy liver tissue with normal trabecular architecture in the treated grafts. Molecular analyses identify the prevention of ischemia-induced decline of cellular autophagy and mitigation of innate immune machinery (high-mobility group protein B1, interferon-β) as operative mechanisms among the protective effects provided by HR.

The pathophysiology of upper airway cough syndrome is not well understood.

ABSTRACTTwo multicenter, open-label, single-arm, two-phase studies evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation (prodrug of penciclovir) in children aged 1 to 12 years with suspicion or evidence of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection. Pooled pharmacokinetic data were generated after single doses in 51 participants (∼12.5 mg/kg of body weight [BW] for children weighing <40 kg and 500 mg for children weighing ≥40 kg). The average systemic exposure to penciclovir was similar (6- to 12-year-olds) or slightly lower (1- to <6-year-olds) than that in adults receiving a 500-mg dose of famciclovir (historical data). The apparent clearance of penciclovir increased with BW in a nonlinear manner, proportional to BW0.696. An eight-step weight-based dosing regimen was developed to optimize exposure in smaller children and was used in the 7-day multiple-dose safety phases of both studies, which enrolled 100 patients with confirmed/suspected viral infections. Twenty-six of 47 (55.3%) HSV-infected patients who received famciclovir twice a day and 24 of 53 (45.3%) VZV-infected patients who received famciclovir three times a day experienced at least one adverse event. Most adverse events were gastrointestinal in nature. Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV (19/21 [90.5%]) or VZV disease (49/53 [92.5%]). Famciclovir formulation (sprinkle capsules in OraSweet) was acceptable to participants/caregivers. In summary, we present a weight-adjusted dosing schedule for children that achieves systemic exposures similar to those for adults given the 500-mg dose.

AbstractSalt domes represent deep geological formations which are under consideration as final repositories for irradiated research reactor fuel elements. For long-term safety aspects the mobilisation of the radionuclides due to a water ingress is intensively investigated. At the Institute of Energy Research (IEF-6), leaching experiments were performed in a hot cell facility with UAlx-Al and U3Si2-Al dispersed research reactor fuel elements in repository-relevant MgCl2-rich salt brines under anaerobic conditions. The fuel plates corroded completely within one year and a Mg-Al-layered double hydroxide (LDH) with chloride as interlayer anion was identified as one crystalline phase component of the corrosion products (secondary phases). This Mg-Al-LDH was synthesized, characterized, and the ability to retard europium by an incorporation process was investigated. Europium, as a representative for lanthanides, was identified to be one of the radionuclides which were found in the corrosion products. We could show that europium was incorporated in the lattice structure. LDHs have high anion exchange capacities that enhance their potential to remove anionic contaminants from aqueous systems.In this work the sorption behaviour of selenium in the chemical form as selenite (SeO32−) on Mg-Al-LDH and on Mg-Al-Eu-LDH was investigated. Especially the influence of the larger europium-III ion was of interest. It represents in the Mg-Al-Eu-LDH about 10% of the molar aluminium amount. The sorption has been experimentally studied in a wide range of pH, ionic strength, radionuclide and sorbent concentration. Both LDHs with chloride as interlayer anion were synthesized by a coprecipitation method under controlled conditions, and their main physico-chemical properties were analyzed prior to the sorption experiments.The sorption kinetics of selenite on the LDHs in water and in MgCl2-rich brine were rapid using a LDH concentration of 10 g/L. Equilibrium, indicated by stable pH values, was obtained within 5 h for an initial selenite concentration of 4.28×10−13mol/L. Selenite in water sorbed quantitatively on both LDHs. In MgCl2-rich brine a different behaviour to water was observed. The sorption was not quantitatively, due to the presence of high amounts of chloride anions. Chloride, as competing anion, affected the sorption behaviour of selenite. Using a LDH concentration of 0.1 g/L, the sorption of selenite was negligible. The effect of pH on selenite sorption was investigated, too. The sorption was relatively constant when the initial pH values were adjusted between 4 and 8, because both LDHs exhibit a high pH buffering capacity. For a selenite concentration range between 5.43×10−14and 3.24×10−12mol/L sorption isotherms were obtained and the data could be fitted to Freundlich and Dubinin–Radushkevich equations. The sorption capacities of the LDHs and the energies of sorption were determined. The sorption of selenite occurred viaan ion exchange mechanism and the sorption behaviour was similar for both LDHs.

The measurement of the fractional concentration of exhaled nitric oxide (FeNO) is a convenient, noninvasive, point-of-service office test for airway inflammation. The first half of this practice management review presents the methodological, interpretative, and clinical applications of FeNO. The second half discusses practical management issues, including current and future technology, equipment specifications, US Food and Drug Administration regulations, cost, current procedural terminology coding, and reimbursement. The measurement of FeNO is helpful in the diagnosis of asthma. It is predictive of a response to inhaled corticosteroids (ICSs). Monitoring FeNO is useful in maintaining asthma control by allowing the assessment of adherence to medication and dose titration of ICSs. An elevated level of FeNO is predictive of asthma relapse following corticosteroid withdrawal especially in children. The advances in technology, ease of use, and clinical utility will lead to greater availability, acceptance, and routine application in the care of asthma.

Die R0-Resektion stellt derzeit die einzige potenziell kurative Therapieform des zentralen Gallengangskarzinoms dar. Die besondere anatomische Lokalisation der Tumoren mit unmittelbarer Nähe zu Leberarterie und Pfortader setzt dabei jedoch operationstechnische Grenzen und schränkt die Übertragbarkeit der Prinzipien der onkologischen Chirurgie ein. Lokale Resektionsverfahren wie die Hepatikusgabelresektion allein oder in Kombination mit limitierten Leberresektionen können mit geringer Morbidität und Mortalität durchgeführt werden, gehen aber mit einer hohen Lokalrezidivrate einher. Ausreichende Sicherheitsabstände können meistens nur durch ausgedehnte Leberresektionen erreicht werden. Die erweiterte Hemihepatektomie rechts („right trisectionectomy“) erlaubt eine weitgehend tumorferne Präparation und ermöglicht die potenziell größten tumorfreien Resektionsränder. Die berichteten 5-Jahre-Überlebensraten liegen zwischen 20% und 40%, in selektionierten Untergruppen sogar bis zu 59%. Die Verfügbarkeit neuer onkologischer Therapieprotokolle sowie insbesondere die Möglichkeit der Leberlebendspende könnten dafür sprechen, dass die Rolle der Lebertransplantation bei diesem Krankheitsbild neu zu definieren ist.Die R0-Resektion stellt derzeit die einzige potenziell kurative Therapieform des zentralen Gallengangskarzinoms dar. Die besondere anatomische Lokalisation der Tumoren mit unmittelbarer Nähe zu Leberarterie und Pfortader setzt dabei jedoch operationstechnische Grenzen und schränkt die Übertragbarkeit der Prinzipien der onkologischen Chirurgie ein. Lokale Resektionsverfahren wie die Hepatikusgabelresektion allein oder in Kombination mit limitierten Leberresektionen können mit geringer Morbidität und Mortalität durchgeführt werden, gehen aber mit einer hohen Lokalrezidivrate einher. Ausreichende Sicherheitsabstände können meistens nur durch ausgedehnte Leberresektionen erreicht werden. Die erweiterte Hemihepatektomie rechts („right trisectionectomy“) erlaubt eine weitgehend tumorferne Präparation und ermöglicht die potenziell größten tumorfreien Resektionsränder. Die berichteten 5-Jahre-Überlebensraten liegen zwischen 20% und 40%, in selektionierten Untergruppen sogar bis zu 59%. Die Verfügbarkeit neuer onkologischer Therapieprotokolle sowie insbesondere die Möglichkeit der Leberlebendspende könnten dafür sprechen, dass die Rolle der Lebertransplantation bei diesem Krankheitsbild neu zu definieren ist.

Dense SiC materials from ultrafine starting powders may be obtained with very limited grain growth if uniaxial hot pressing with concurrent lateral flow of the sample is applied. This process, termed sinter forging, allows to decouple the kinetics of densification and grain growth owing to the elimination of the largest and most persistent population of pores by viscous deformation under the action of shear forces.

Zusammenfassung Verletzungen des Tracheobronchialbaums nach stumpfem Thoraxtrauma sind mit unter 1% relativ seltene Ereignisse. Diagnostik und Behandlung stellen aufgrund ihrer Rarität an den erstbehandelnden Arzt hohe Anforderungen; wird die Verletzung nicht rechtzeitig erkannt, können lebensgefährliche Komplikationen drohen. Im Folgenden wird der Fall eines 9-jährigen Mädchen beschrieben, das durch den Sturz auf den Lenker ihres Kickboards einen zervikalen Trachealeinriss im Bereich des Paries membranaceus erlitten hatte. Anhand dieses Falls sollen die diagnostischen Möglichkeiten der Tracheoskopie bzw. Computertomographie dargestellt werden. Ferner wird die Möglichkeit des von uns durchgeführten konservativen Behandlungsregimes diskutiert.

The main goals of asthma therapy are to control symptoms, prevent acute attacks, and maintain lung function as close to normal as possible. Customizing the regimen to relieve the patient's symptoms and control airway inflammation is important. If asthma is not well controlled, an initial inhaled corticosteroid boost will treat the underlying heightened airway inflammation, and the addition of a long-acting β2-adrenergic agonist or leukotriene receptor antagonist will rapidly control symptoms. Most patients do not require prolonged treatment with expensive combination or additive agents. Exercise-induced bronchoconstriction is a common source of symptoms. Treatments for scheduled and unscheduled exercises differ. Inhaled corticosteroids prevent frequent and severe asthma exacerbations. When patients have persistent symptoms despite a pharmacological regimen, environmental factors and nonpharmacological interventions must be considered before medication is increased. When an inhaled corticosteroid is being considered, issues of compliance, drug delivery device, and proper inhaler techniques are as important as issues of potency, clinical efficacy, and adverse effects. The new hydrofluoroalkane preparations offer more lung deposition and may be important in treating inflammation of the small airways in patients with asthma.