Validation of modular endoscopic medial maxillectomies for inverted papilloma of the maxillary sinus.

BACKGROUND: Treatment of inverted papilloma of the maxillary sinus (IPMS) has a lower success rate compared to other IPs. As such, its correct management generally needs trans-nasal endoscopic medial maxillectomy (EMMs) for adequate resection. The aim of this manuscript is to describe outcomes and major prognostic factors of a cohort of patients with IPMS who were treated with EMM. METHODOLOGY: In this multicentric study, patients affected with IPMS and treated with EMMs were included. The site of origin of the IPMS were studied as well as the type of EMM performed. The histological features (IP vs dysplasia), type of mucosal resection (total vs. pedicle oriented), and post-operative complications were analyzed. RESULTS: 310 patients were included (212 primary and 98 recurrent cases). After a mean follow-up of 45.4 months, 15 patients experienced recurrence (4.8%) due to the application of EMMs tailored to the surgical insertion point. Dysplasia was significantly associated with a higher risk of recurrence. The rates of early and late complications were 11.6% and 11.9%, respectively. CONCLUSIONS: IPMS resection via tailored EMM is associated with excellent disease control, thus excluding the systematic use of extended EMMs, which can however be justified in case of dysplastic IPMS given its significant impact on recurrence.

Hemophagocytic lymphohistiocytosis and thrombotic microangiopathy after parvovirus B19 infection and renal transplantation: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disease characterized by hyperactivation of the immune system that causes hypercytokinemia and potentially multi organ failure. HLH can occur in patients with underlying rheumatic or autoinflammatory disorders. Additionally, HLH can develop in patients during infections or malignancies without a known genetic predisposition. CASE PRESENTATION: We herein report a patient, who presented with fever, both acute kidney and liver injury, anemia, thrombocytopenia and HSV stomatitis. HLH was diagnosed based on clinical criteria and qPCR revealed an acute parvovirus B19 infection as potential underlying infectious trigger. Treatment was started with both IVIG and dexamethasone. Subsequently, kidney biopsy demonstrated TMA. CONCLUSIONS: In rare cases both HLH and aHUS can occur simultaneously in a patient as a consequence of viral infections. Insights from this unusual case might help physicians understand this complex symptom constellation.

The global transcriptomic signature in sinonasal tissues reveals roles for tissue type and chronic rhinosinusitis disease phenotype.

BACKGROUND: RNA sequencing (RNA-Seq) allows the characterization of a global transcriptomic signature in a least-biased fashion, but few studies have applied this method to investigate the pathophysiology of CRS. METHODS: We collected mucosal tissue samples from 6 CRS without nasal polyps (CRSsNP), 6 CRS with nasal polyps (CRSwNP), and 6 control patients. Additional matched polyp samples were collected from the 6 CRSwNP patients. RNA was extracted and sequenced on the Illumina HiSeq-2500. Differential gene expression and pathway analyses were performed. RESULTS: CRSsNP showed evidence of upregulated interferon-mediated immunity, MHC-class-I mediated antigen presentation, CXCR3 binding, neutrophil chemotaxis and degranulation, and potential downregulation of genes related to cilia movement and production. CRSwNP polyp tissue showed upregulation of B-cell mediated immune responses, but reduced expression of genes related to epithelial morphogenesis and haemostasis. Polyps also showed a generalized reduction of positive gene regulation. The sinonasal transcriptomic signature was largely determined by tissue type (polyp versus mucosa) and disease phenotype, with minimal signal originating from the individual patient. CONCLUSION: RNA-Seq is a useful tool to explore the complex pathophysiology of CRS. Our findings stress the importance of tissue selection in molecular research utilizing sinonasal tissue, and demonstrate the limitation of the sNP/wNP paradigm (and the importance of endotyping). On the other hand, classical CRSsNP/wNP disease phenotypes played some role in determining the global transcriptomic signature, and should not be hastily discarded. The value of RNA-Seq-described transcriptomic signatures in exploring endotypes is yet to be explored in future studies.

Postoperative long-term morbidity of extended endoscopic maxillectomy for inverted papilloma.

BACKGROUND: Extended endoscopic maxillectomy (Sturmann-Canfield procedure) allows full visualization of the maxillary sinus by sectioning the lacrimal duct and removing the medial part of the anterior maxillary wall. The aim of this study is to evaluate the morbidity of Sturmann-Canfield procedure in patients treated for inverted papilloma. METHODOLOGY: The clinical records of all patients treated with a Sturmann-Canfield procedure for inverted papilloma from October 2000 to September 2015 at two teaching hospitals were reviewed. All patients were evaluated by nasal endoscopy and lacrimal system patency was assessed. Pre-maxillary cutaneous sensitivity was tested with a Semmes-Weinstein aesthesiometer and thermic stimulation. The SNOT-22 questionnaire was administered. Patients were also asked to report any other post-surgical complaints. RESULTS: Fifty-nine patients were identified. Mean follow-up after surgery was 66.3 months. Mean SNOT-22 score was 5.94 (range 0-20); the majority of patients (86%) had a SNOT-22 symptom score of 3 or lower. Mucocoele occurred in 3 (5%) cases. Lacrimal pathway obstruction was observed in 7 (12%) patients. Fourteen (24%) patients complained of paraesthesia in the malar area; hypoesthesia was present in only 5 (8%) cases. Hypoesthesia in the region innervated by the anterior superior alveolar nerve was detected in 17 (29%) patients. One patient reported a slight depression of paralateronasal soft tissues. CONCLUSIONS: Although nasal function outcomes and the results from SNOT-22 questionnaires were favourable, a high rate of neurologic and lacrimal complications was observed. Potential morbidity of the intervention, including the possibility of negative aesthetic sequelae, should be discussed during preoperative counselling.

STEM EDX Nitrogen Mapping of Nanoinclusions in Milky Diamonds from Juina, Brazil, Using a Windowless Silicon Drift Detector System.

Energy-dispersive X-ray spectroscopy (EDX) performed using scanning transmission electron microscopy (STEM) in combination with a windowless detector setup allows high-resolution imaging and chemical composition mapping even of light elements present in low concentrations. The used TEM-system combines a field emission electron source with four silicon drift detectors allowing for high detection sensitivity. We used this enhanced system to investigate 20 to 200 nm sized inclusions in milky diamonds from Rio Soriso, Juina area, Brazil. The diamonds act as a chemical inert container and therefore protect their inclusions from further chemical reactions with their surroundings. We visualize the presence and distribution of nitrogen within focused ion beam (FIB) slices containing these nanoinclusions. The investigation of these specific diamonds may open a new window to deeper parts of the Earth (>660 km) as they represent pristine material of this deep mantle environment.

Severe Paracoccidioidomycosis in a 14-Year-Old Boy.

Paracoccidioidomycosis (PCM) is the most important systemic mycoses in Latin America. We describe a severe case of paracoccidioidomycosis in a 14-year-old boy, with a rapid disease progression. The fungal strain was isolated and inoculated into a T and/or B cell immunocompromised mice, which revealed a highly virulent strain. The case report presented herein emphasizes the importance of considering PCM in the differential diagnosis of patients with other infectious diseases in endemic areas and highlights a novel isolate.

Expanded endoscopic endonasal surgery for advanced stage juvenile angiofibromas: a retrospective multi-center study.

OBJECTIVES: Endoscopic resection has become an established surgical option for most juvenile nasopharyngeal angiofibromas (JNA). However, surgical management of JNA with intracranial extension remains challenging. This retrospective multicenter study reviews a series of patients with advanced stage JNA treated via endonasal/endoscopic approach. METHODS: The experience of five academic tertiary or quaternary care ORL-HNS Departments were included. Medical records of all patients operated for JNA staged as Radkowski stage IIIA or IIIB were reviewed. Main outcome measures included intraoperative blood loss, length of hospital stay, complication rate, and rate of persistence or recurrence. RESULTS: A total of 74 male patients with stages IIIA and IIIB were included. The mean age was 16.4 years and preoperative embolization was performed in 71 patients. The mean blood loss in 45 patients for whom the data was available was 1279.7 ml. The more anatomic subsites were involved, the higher the risk was of intraoperative bleeding. The mean follow-up for 54 out of 73 patients was 37.9 months. Patients with residual disease are significantly linked to involvement of combined (anterior-lateral and posterior) anatomic subsites and to a higher number of affected subsites. At last follow-up, all patients were asymptomatic and those with residual tissue displayed no imaging signs of growth. CONCLUSIONS: This retrospective multicenter study supports the notion that expanded endonasal endoscopic approaches for advance staged JNA are a feasible option associated with good long-term results.

[Development and implementation of a state-wide "train the trainer" model of the school-based prevention programme "Join the Healthy Boat - Primary School"]. / Entwicklung und Implementierung eines landesweiten Multiplikatorensystems zur flächendeckenden Umsetzung des schulbasierten Präventionsprogramms "Komm mit in das gesunde Boot - Grundschule"

STUDY AIM: This paper shows how a state-wide health-promotion intervention at primary schools can be implemented by considering the example of the programme "Join the Healthy Boat - Primary School". Additionally, it is illustrated how quality control throughout the whole process can be incorporated. METHODS: To operate long-term and target-group orientated in the whole state of Baden-Württemberg, the school-based prevention programme "Join the Healthy Boat" uses a "train the trainer" model. The trainers are teachers who were instructed by the project team. In the school year 2009/10, these trainers offered quadrinominal training courses for further teachers. Every urban and rural district is covered by 1 trainer. The trainers evaluated the 6 preparatory training courses they had been given using questionnaires. The following 4 training courses the trainers offered to the teachers were reviewed by the trainers as well as the teachers using questionnaires, too. Additionally, at the end of the school year 2009/10, the teachers completed a questionnaire about their satisfaction regarding the programme itself and the work with the trainer. RESULTS: During the school year 2009/10, 453 teachers were trained by 32 trainers. According to indications on the questionnaires about the preparatory training courses, all trainers felt themselves "very well" or "well" prepared for their task. The teachers evaluated the expertise of the respective trainer, the quality of the training courses and the satisfaction with the programme itself throughout highly. CONCLUSION: Based on the excellent results of the process evaluation and the programme's wide coverage, an adoption of a "train the trainer" model seems worthwhile for other school-based prevention programmes, as well.

Physiological changes during low- and high-intensity noninvasive ventilation.

In a physiological randomised cross-over study performed in stable hypercapnic chronic obstructive disease patients, we assessed the short-term effects of two settings of noninvasive ventilation. One setting was aimed at maximally reducing arterial carbon dioxide tension (P(a,CO(2))) (high-intensity (Hi) noninvasive positive pressure ventilation (NPPV)): mean ± SD 27.6 ± 2.1 cmH(2)O of inspiratory positive airway pressure, 4 ± 0 cmH(2)O of expiratory positive airway pressure and respiratory rate of 22 breaths · min(-1). The other was performed according to the usual parameters used in earlier studies (low-intensity (Li)-NPPV): 17.7 ± 1.6 cmH(2)O of inspiratory positive airway pressure, 4 ± 0 cmH(2)O of expiratory positive airway pressure and respiratory rate of 12 breaths · min(-1). Both modes of ventilation significantly improved gas exchange compared with spontaneous breathing (SB), but to a greater extent using Hi-NPPV (P(a,CO(2)) 59.3 ± 7.5, 55.2 ± 6.9 and 49.4 ± 7.8 mmHg for SB, Li-NPPV and Hi-NPPV, respectively). Similarly, Hi-NPPV induced a greater reduction in the pressure-time product of the diaphragm per minute from 323 ± 149 cmH(2)O · s · min(-1) during SB to 132 ± 139 cmH(2)O · s · min(-1) during Li-NPPV and 40 ± 69 cmH(2)O · s · min(-1) during Hi-NPPV, while in nine out of 15 patients, it completely abolished SB activity. Hi-NPPV also induced a marked reduction in cardiac output (CO) measured noninvasively with a Finometer PRO (Finapres Medical Systems BV, Amsterdam, the Netherlands) compared with Li-NPPV. We conclude that while Hi-NPPV is more effective than Li-NPPV in improving gas exchange and in reducing inspiratory effort, it induces a marked reduction in CO, which needs to be considered when Hi-NPPV is applied to patients with pre-existing cardiac disease.

Organic synthesis associated with serpentinization and carbonation on early Mars.

Water-rock interactions are relevant to planetary habitability, influencing mineralogical diversity and the production of organic molecules. We examine carbonates and silicates in the martian meteorite Allan Hills 84001 (ALH 84001), using colocated nanoscale analyses, to characterize the nature of water-rock reactions on early Mars. We find complex refractory organic material associated with mineral assemblages that formed by mineral carbonation and serpentinization reactions. The organic molecules are colocated with nanophase magnetite; both formed in situ during water-rock interactions on Mars. Two potentially distinct mechanisms of abiotic organic synthesis operated on early Mars during the late Noachian period (3.9 to 4.1 billion years ago).

Amorphous calcium carbonate in the shells of adult Unionoida.

Shells of adult individuals from two different bivalve families, Hyriopsis cumingii and Diplodon chilensis patagonicus, were studied by Micro-Raman spectroscopy and Focussed Ion Beam-assisted TEM. The shells contain amorphous calcium carbonate in a zone at the interface between the periostracum and the prismatic layer. In this area, the initial prism structures protrude from the inner periostracum layer and it is demonstrated that these structures systematically consist of highly disordered and amorphous calcium carbonate. Within this zone, ordered and disordered areas are intermingled discounting the existence of a crystallization front and favouring models of domainal crystallization processes via so-called mesocrystals. These observations are the first documentation of the use of amorphous calcium carbonate as a precursor phase by adult mollusc species and lend further support to hypotheses postulating widespread use of amorphous phases as building material of skeletal tissue in biology.

Decoherence and disorder in quantum walks: from ballistic spread to localization.

We investigate the impact of decoherence and static disorder on the dynamics of quantum particles moving in a periodic lattice. Our experiment relies on the photonic implementation of a one-dimensional quantum walk. The pure quantum evolution is characterized by a ballistic spread of a photon's wave packet along 28 steps. By applying controlled time-dependent operations we simulate three different environmental influences on the system, resulting in a fast ballistic spread, a diffusive classical walk, and the first Anderson localization in a discrete quantum walk architecture.

Adhesion formation after previous caesarean section-a meta-analysis and systematic review.

BACKGROUND: The optimal technique for performing caesarean section with respect to minimising postoperative adhesions has not been determined. OBJECTIVES: To evaluate adhesion formation for three common caesarean section techniques in women undergoing repeat caesarean section surgeries. SEARCH STRATEGY: A database was constructed from Medline, EMBASE, Cochrane Library, National Science Digital Library, China Biological Medicine Database and through contact with experts in this field from January 1990 to May 2010. SELECTION CRITERIA: Studies were included if they examined adhesion formation in repeat caesarean sections as a primary objective, delineated a clear study design, specified an adhesion scoring system, and had sufficient patient exclusion criteria. DATA COLLECTION AND ANALYSIS: We abstracted data regarding adhesion formation. The Mantel-Haenszel random-effects model was employed for all analyses using odds ratio or inverse variance, along with 95% CI. MAIN RESULTS: Thirty-three qualified studies including 4423 women were analysed. There were 406 adhesions among 571 women and 238 adhesions among 596 women in the Stark's caesarean section (also known as Misgav-Ladach method) group and modified Stark's caesarean section group, respectively, with pooled OR 4.69 (95% CI 3.32-6.62; P < 0.01, 12 studies); 1173 adhesions among 1555 women and 1179 adhesions among 1625 women in Stark's caesarean section group and classic lower-segment caesarean section group, respectively, with pooled odds ratio 1.28 (95% CI 0.97-1.68; P = 0.08, 21 studies); and 29 adhesions from 102 women and 115 adhesions from 193 women in modified Stark's caesarean section group and classic lower-segment caesarean section group, respectively, with pooled odds ratio 0.28 (95% CI 0.10-0.82; P = 0.02, two studies). AUTHORS' CONCLUSIONS: Closure of the peritoneum in modified Stark's caesarean section resulted in less adhesion formation and should be recommended.

Thyroid hormone-responsive genes mediate otolith growth and development during flatfish metamorphosis.

Flatfish begin life as up-right swimming, bilaterally symmetrical larvae that metamorphose into asymmetrically shaped juveniles that swim with a highly lateralized posture. We have previously shown that TH induces abrupt growth and mineralization of one component of the vestibular system, the otoliths, during early larval development and metamorphosis. Here we report that four of five vestibular-specific genes that we tested (alpha-tectorin, otogelin, otolith matrix protein, and otopetrins 1 and 2 that are known to be associated with otolith development in other vertebrates are up-regulated 1.5- to 7-fold in larval flatfish during spontaneous metamorphosis and/or following 72 h of TH treatment. These findings suggest that otolith growth and development are mediated by diverse TH-responsive genes during flatfish metamorphosis.

Revision of the common bile duct in a combined PTCD/ERC approach - A case report.

INTRODUCTION AND IMPORTANCE: The endoscopic retrograde cholangiography (ERC) represents the standard treatment for choledocholithiasis. However, ERC in patients with previous gastrectomy and anastomosis is difficult due to altered access. CASE PRESENTATION: In our case, we report on a patient with previous gastrectomy and Y-Roux-anastomosis suffering from choledocholithiasis. Operative revision with simultaneous cholecystectomy failed. In a combined procedure of percutaneous transhepatic cholangiodrainage (PTCD) and endoscopic cholangiography the stone removal of the common bile duct was finally successful. CLINICAL DISCUSSION: There are some approaches for treatment of choledocholithiasis in pre-operated patients. However, prospective multi-center studies for complication and success rates are not available due to the rarity of such cases. CONCLUSION: Interdisciplinary procedures seem to be the safest and most promising way to succeed in the treatment of choledocholithiasis in challenging cases.

Strain wave pathway to semiconductor-to-metal transition revealed by time-resolved X-ray powder diffraction.

One of the main challenges in ultrafast material science is to trigger phase transitions with short pulses of light. Here we show how strain waves, launched by electronic and structural precursor phenomena, determine a coherent macroscopic transformation pathway for the semiconducting-to-metal transition in bistable Ti3O5 nanocrystals. Employing femtosecond powder X-ray diffraction, we measure the lattice deformation in the phase transition as a function of time. We monitor the early intra-cell distortion around the light absorbing metal dimer and the long range deformations governed by acoustic waves propagating from the laser-exposed Ti3O5 surface. We developed a simplified elastic model demonstrating that picosecond switching in nanocrystals happens concomitantly with the propagating acoustic wavefront, several decades faster than thermal processes governed by heat diffusion.

Rho is required for the initiation of calcium signaling and phagocytosis by Fcgamma receptors in macrophages.

Phagocytosis of bacteria by macrophages and neutrophils is an essential component of host defense against infection. The mechanism whereby the interaction of opsonized particles with Fcgamma receptors triggers the engulfment of opsonized particles remains incompletely understood, although activation of tyrosine kinases has been recognized as an early step. Recent studies in other systems have demonstrated that tyrosine kinases can in turn signal the activation of small GTPases of the ras superfamily. We therefore investigated the possible role of Rho in Fc receptor-mediated phagocytosis. To this end we microinjected J774 macrophages with C3 exotoxin from Clostridium botulinum, which ADP-ribosylates and inactivates Rho. C3 exotoxin induced the retraction of filopodia, the disappearance of focal complexes, and a global decrease in the F-actin content of J774 cells. In addition, these cells exhibited increased spreading and the formation of vacuolar structures. Importantly, inactivation of Rho resulted in the complete abrogation of phagocytosis. Inhibition of Fcgamma receptor-mediated phagocytosis by C3 exotoxin was confirmed in COS cells, which become phagocytic upon transfection of the FcgammaRIIA receptor. Rho was found to be essential for the accumulation of phosphotyrosine and of F-actin around phagocytic cups and for Fcgamma receptor-mediated Ca2+ signaling. The clustering of receptors in response to opsonin, an essential step in Fcgamma-induced signaling, was the earliest event shown to be inhibited by C3 exotoxin. The effect of the toxin was specific, since clustering and internalization of transferrin receptors were unaffected by microinjection of C3. These data identify a role for small GTPases in Fcgamma receptor-mediated phagocytosis by leukocytes.

Phase I trial of dose-escalated cisplatin with concomitant cetuximab and hyperfractionated-accelerated radiotherapy in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Cetuximab is active in the treatment of squamous cell carcinoma of the head and neck (SCCHN), enhancing both radiotherapy and chemotherapy effects. This phase I study was designed to investigate the safety and tolerability of combining weekly cisplatin treatment with cetuximab and hyperfractionated-accelerated radiotherapy (HART) for locally advanced SCCHN. PATIENTS AND METHODS: Patients with unresectable stage III or IVA/B SCCHN were treated with cetuximab, 400 mg/m² initial dose on day -7 of HART, followed by 250 mg/m² weekly during the administration of HART, which started with 2.0 Gy/day (5 days/week) for 3 weeks followed by 1.4 Gy/twice-daily (Monday to Friday) for another 3 weeks, resulting in a total dose of 70.6 Gy. Cisplatin was administered weekly starting on the first day of radiotherapy until week 6. Cisplatin was dose escalated of four dose levels from 20 to 40 mg/m² using a classical 3 + 3 dose escalation algorithm. RESULTS: Eighteen patients were enrolled. Sixteen patients were eligible for toxicity, and 15 for response. No maximum tolerated dose was reached for cisplatin. One of six patients of dose level 4 had grade 4 neutropenia. This patient died 1 week after the end of the study treatment. The most common types of grade 3+ adverse events were mucositis (9 of 16 patients), in-field dermatitis (6 of 16 patients) and neutropenia (4 of 16 patients). Cetuximab-related hypersensitivity was observed in 1 out of 18 patients. Six weeks after the end of the study treatment, 5 complete responses, 8 partial responses and 1 progressive disease (at distant sites) were documented in a total of 15 patients (objective response rate 87%). CONCLUSIONS: The combination of cisplatin with cetuximab and HART is active, well tolerated and merits additional investigation. The recommended weekly dose of cisplatin for phase II studies is 40 mg/m².