Functional outcomes and complications in refractory dysthyroid optic neuropathy management: Experience with 3 different surgical protocols.

INTRODUCTION: Dysthyroid optic neuropathy (DON) is the most severe complication of Graves' orbitopathy (GO) and its management may require decompression surgery. Clear recommendations do not exist about which surgery should be performed and how extended the decompression should be. In this paper we present our experience regarding the management of DON via 3 different surgical protocols: a modified extended orbital apex decompression, a 2 walls decompression (inferior and lateral) and a 3 walls decompression (inferior, lateral and medial) and evaluate the functional outcomes. METHODS: Retrospective evaluation of subjects affected by DON not responding to medical therapy has been performed. All patients were submitted to pre- and post-operative ophthalmologic evaluations and orbital and sinuses CT scan in order to evaluate functional and surgical outcomes. RESULTS: 27 patients were enrolled in the study. Surgical procedures were performed on 42 orbits. A statistically significant post-operative improvement was recorded in visual acuity, proptosis, color vision and fundus oculi evaluation for all groups. No patient developed major or minor complications after surgery. CONCLUSIONS: Extended endonasal approach and 3 walls decompression have been proved effective in the management of DON. The choice between them is done according to degree of proptosis, general status and eye-surface damages.

An Experimental Ultrasound System for Qualitative Tomographic Imaging.

The advancement of new promising techniques in the field of biomedical imaging has always been paramount for the research community. Recently, ultrasound tomography has proved to be a good candidate for non-invasive and safe diagnostics. In particular, breast cancer imaging may benefit from this approach, as frequent screening and early diagnosis require decreased system size and costs compared to conventional imaging techniques. Furthermore, a major advantage of these approaches consists in the operator-independent feature, which is very desirable compared to conventional hand-held ultrasound imaging. In this framework, the authors present some imaging results on an experimental campaign acquired via an in-house ultrasound tomographic system designed and built at the University of Naples Parthenope. Imaging performance was evaluated via different tests, showing good potentiality in structural information retrieval. This study represents a first proof of concept in order to validate the system and to consider further realistic cases in near future applications.

Vesicular monoamine transporters expression in pheochromocytomas and paragangliomas according to scintigraphy and positron emission tomography behavior.

BACKGROUND: The expression of vesicular catecholamine transporters (VMAT1 and 2) in pheochromocytomas (PHEOs) and paragangliomas (PGLs) and the possible relationships with [18F]FDOPA PET/CT and [123I]MIBG scintigraphy uptake are unknown. Our purpose was to investigate possible correlations of either VMAT1 and VMAT2 expression with the functional imaging in patients with PHEOs and PGLs. METHODS: An observational 3-year time study was performed by enrolling 31 consecutive patients with PHEO (N.=17) or PGL (N.=14). They underwent the same diagnostic work-up; moreover, [123I]MIBG SPECT/CT (N.=20) and [18F]FDOPA PET/CT (N.=14) were performed in a subset of patients. After surgery, routine histology and semiquantitative analysis of VMAT1/VMAT2 immunoreactivity were carried out in all cases. RESULTS: VMAT1 immunoreactivity was found in all tumors, but two PHEOs. VMAT1 immunoreactivity was higher in PGLs than in PHEOs, though at not significant extent. Elevated VMAT2 immunoreactivity score was present in all but two negative tumors. Normal [123I]-MIBG uptake was independent from VMAT1/2 immunoreactivity. Patients undergoing [18F]FDOPA PET/CT showed a high score level of both VMATs and were detected by the technique in all cases. CONCLUSIONS: VMAT1 and VMAT2 are highly expressed in most tumors, though VMAT1 immunoreactivity is apparently prevalent in PGLs as compared to PHEOs. Presence and expression of VMAT1 and VMAT2 are not limiting factors for MIBG uptake. The status of VMAT expression might help to understand why the more frequently used radiotracers do not always have the expected diagnostic performance. Finally, the present study points out the importance of developing new radiotracers with higher sensitivity, specificity and accuracy consequently reducing healthcare costs.

Graves' orbitopathy: a multidisciplinary approach.

Orbitopathy is the main extra thyroidal manifestation of Graves' disease. It is a very challenging condition, which requires a cooperation between many specialists (endocrinologists, ophthalmologists, radiologists, radiotherapeutic, orbital surgeons) for an optimal clinical management. An accurate diagnostic assessment is required, in order to plan an adequate treatment of Graves' orbitopathy. Medical therapy, radiotherapy or surgery may be necessary to control the disease. In this review, the authors analyze the various therapeutic strategies, as well the more recent therapies based on pharmacologic immunomodulation.

Focus on the Involvement of the Nose and Paranasal Sinuses in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Nasal Cytology Reveals Infiltration of Eosinophils as a Very Common Feature.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis that predominantly affects small- to medium-sized vessels. It is characterized by a wide spectrum of extrapulmonary symptoms, including sinonasal and paranasal sinus abnormalities. These are the most common features of this disease, constituting diagnostic criteria for EGPA. However, the actual clinical features, cellular mechanisms and impact on patients' quality of life (QoL) are still a matter of study. METHODS: Thirty-nine EGPA patients underwent multidimensional rhinological evaluations, including rhinofibroscopy, nasal cytology, and QoL questionnaires. This was coupled with respiratory and rheumatological assessments. RESULTS: Twenty-eight patients were diagnosed with chronic rhinosinusitis (CRS). Of these, 18 had nasal polyposis (NP). Chronic rhinitis was diagnosed in 10 patients. Of these, 3 had allergic rhinitis (AR) and seven had non-AR (NAR). Overall, only 1 patient (2.6%) was normal. Nasal cytology showed that hypereosinophilia was present in 17/28 patients with CRS, 4/7 patients with NAR and all patients with AR. SNOT-22 and SF-36 showed a severe impact of nasal symptoms on QoL. No differences in asthma control or rheumatological patterns for EGPA were observed among patients with or without NP. CONCLUSIONS: Even when the rheumatological assessment scored EGPA "under control" according to the Birmingham Vasculitis Activity Score and Vasculitis Damage Index, sinonasal diseases and related nasal inflammatory processes were not controlled. Therefore, there is a need for clinical monitoring and targeted treatment to control the inflammatory processes and improve the QoL of EGPA patients.

Frey Syndrome, First Bite Syndrome, great auricular nerve morbidity, and quality of life following parotidectomy.

PURPOSE: Parotidectomy may be burdened by numerous complications that may worsen subjects' quality of life (QoL). These include paresis or paralysis of the facial nerve, face profile asymmetry, keloids, salivary fistula, Frey Syndrome (FS), First Bite Syndrome (FBS), and hypo-anaesthesia of the skin. This study is an effort to assess the incidence of complications following parotidectomy and their impact on subjects' QoL. METHODS: Subjects undergoing parotidectomy for benign neoplasms from 2012 to 2015 were selected and invited to attend our outpatient clinic. After a brief anamnesis, the medical examiners tested their tactile perception and performed the Minor test for FS. Depending on the complications showed, subjects were asked to complete from 1 to 4 questionnaires about their QoL. RESULTS: 76 subjects completed the medical examination. The most frequent complication was the hypo-anaesthesia of the skin (71%). 21 subjects (28%) were positive to the Minor test, while 8 subjects (11%) reported FBS-compatible symptoms. Two subjects (3%) showed a facial nerve paralysis. Free abdominal fat graft was used in 16 subjects (21%) and it was associated with a lower incidence of FS. Surgery of the deep lobe of the parotid was associated with FBS. CONCLUSIONS: FBS appears to have a greater influence on subjects' QoL than FS and hypo-anaesthesia of the skin. Moreover, this work confirms that surgery of the deep lobe of the parotid is a risk factor for developing FBS and the free abdominal fat graft is a reliable technique to prevent FS.

Endoscopic-assisted transoral-transpharyngeal approach to parapharyngeal space and infratemporal fossa: focus on feasibility and lessons learned.

The parapharyngeal space (PPS) is a challenging anatomical region, rich in vascular and nervous vital structures. Surgery is considered the treatment of choice for the majority of PPS lesions. Herein, we present a retrospective evaluation on ten patients with various types of lesions of the parapharyngeal and infratemporal fossa (ITF) regions operated on via an endoscopic-assisted transoral-transpharyngeal approach (EATTA), focusing on feasibility and safety. A retrospective evaluation of patients treated by means of EATTA to PPS and/or ITF lesions was carried out. The clinical records of patients who were operated on with EATTA for PPS and/or ITF lesions between March 2009 and October 2015 at two referral centres were reviewed and the intra-operative and post-operative complications were analysed. Ten patients who underwent EATTA on the PPS and ITF were included in this series. The procedure was performed in six patients for tumour removal, in three patients for diagnostic purposes and in one patient for pain control. No major complications occurred. No conversion to external approach was required. We observed only two minor complications which were promptly solved. No dysphagia or other problems during the food intake were observed in our series. One day after surgery all patients, except one, referred a value of VAS minor than 4. To date, no evidence of disease recurrence has been assessed in all six oncological cases. Although preliminary, our experience seems to demonstrate the feasibility and safety of EATTA when properly planned and performed.

Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA.

Siderophore A (SidA) is a flavin-dependent monooxygenase that catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of ornithine in the biosynthesis of siderophores in Aspergillus fumigatus and is essential for virulence. SidA can utilize both NADPH or NADH for activity; however, the enzyme is selective for NADPH. Structural analysis shows that R279 interacts with the 2'-phosphate of NADPH. To probe the role of electrostatic interactions in coenzyme selectivity, R279 was mutated to both an alanine and a glutamate. The mutant proteins were active but highly uncoupled, oxidizing NADPH and producing hydrogen peroxide instead of hydroxylated ornithine. For wtSidA, the catalytic efficiency was 6-fold higher with NADPH as compared to NADH. For the R279A mutant the catalytic efficiency was the same with both coenyzmes, while for the R279E mutant the catalytic efficiency was 5-fold higher with NADH. The effects are mainly due to an increase in the KD values, as no major changes on the kcat or flavin reduction values were observed. Thus, the absence of a positive charge leads to no coenzyme selectivity while introduction of a negative charge leads to preference for NADH. Flavin fluorescence studies suggest altered interaction between the flavin and NADP⁺ in the mutant enzymes. The effects are caused by different binding modes of the coenzyme upon removal of the positive charge at position 279, as no major conformational changes were observed in the structure for R279A. The results indicate that the positive charge at position 279 is critical for tight binding of NADPH and efficient hydroxylation.

Probing the activity of diguanylate cyclases and c-di-GMP phosphodiesterases in real-time by CD spectroscopy.

Bacteria react to adverse environmental stimuli by clustering into organized communities called biofilms. A remarkably sophisticated control system based on the dinucleotide 3'-5' cyclic diguanylic acid (c-di-GMP) is involved in deciding whether to form or abandon biofilms. The ability of c-di-GMP to form self-intercalated dimers is also thought to play a role in this complex regulation. A great advantage in the quest of elucidating the catalytic properties of the enzymes involved in c-di-GMP turnover (diguanylate cyclases and phosphodiesterases) would come from the availability of an experimental approach for in vitro quantification of c-di-GMP in real-time. Here, we show that c-di-GMP can be detected and quantified by circular dichroism (CD) spectroscopy in the low micromolar range. The method is based on the selective ability of manganese ions to induce formation of the intercalated dimer of the c-di-GMP dinucleotide in solution, which displays an intense sigmoidal CD spectrum in the near-ultraviolet region. This characteristic spectrum originates from the stacking interaction of the four mutually intercalated guanines, as it is absent in the other cyclic dinucleotide 3'-5' cyclic adenilic acid (c-di-AMP). Thus, near-ultraviolet CD can be used to effectively quantify in real-time the activity of diguanylate cyclases and phosphodiesterases in solution.

Transorbital endoscopic assisted resection of a superior orbital fissure cavernous haemangioma: a technical case report.

OBJECTIVES: Superior orbital fissure and orbital apex lesions are challenging to manage, regardless of the approach chosen, due to the potential morbidity. The objectives of this study are to describe an innovative, minimally invasive surgical approach addressing this critical area and to discuss its indications and outcomes. SUBJECT: A young patient presented with visual disturbances (reduction of color discrimination, central scotoma) and mild exophthalmos owing to the presence of a right orbital apex cavernous haemangioma with superior orbital fissure invasion. METHODS: The lesion was removed via a minimally invasive, neuronavigated, transorbital superior eyelid endoscopic-assisted approach. MAIN OUTCOME MEASURES: Technical feasibility and safety, early and late complications, length of hospitalization time and follow-up data were collected and analyzed. RESULTS: The lesion was radically resected minimizing the surgical morbidity and hospitalization time for the patient and with encouraging functional and cosmetic outcomes. No recurrences were observed 1 year after surgery. CONCLUSIONS: The endoscopic-assisted transorbital approach should be considered a safe and effective option that can be applied in the treatment of lesions affecting such complex anatomical regions, as it offers excellent visualization of the surgical field, acceptable sequelae and reduced morbidity in relation to the traditional transcranial/transfacial approaches. Further studies and larger case series are needed in order to validate the reproducibility and range of applications of this surgical technique.

Quantitative study on endoscopic endonasal approach to the posterior sino-orbito-cranial interface: implications and clinical considerations.

The posterior sino-orbito-cranial interface is a critical area in the skull base since it represents a gateway to deeper vital regions. Quantification of the surgical freedom for any given point/area is an objective method for comparing in a reproducible way different surgical approaches. Three freshly injected cadaver heads (six sides) were dissected under the magnetic navigation control system. The surgical freedom (SF) and the angle of attack of fixed target points were determined from the ipsilateral nasal fossa, from the contralateral nasal fossa (after posterior septectomy), and after an anteromedial maxillotomy (according to the Denker procedure). The mean pre-operative SF value resulted to be 403.07 ± 102.73 mm(2) for the ipsilateral nostril, increasing by 126.97 % for the binostril approach, by 118.45 % for the monolateral nostril approach after anteromedial maxillotomy, and by 310.48 % for the binostril approach after bilateral anteromedial maxillotomy. Laterally extended lesions require an anteromedial maxillotomy, while more medially located lesions can be managed by means of a posterior septectomy. When addressing the posterior sino-orbito-cranial interface, the transnasal binostril approach and anteromedial maxillotomy both increase the SF. The choice between them depends on exact position, relationship and clinical behaviour of the lesion to treat.

Exploring the structural basis of substrate preferences in Baeyer-Villiger monooxygenases: insight from steroid monooxygenase.

Steroid monooxygenase (STMO) from Rhodococcus rhodochrous catalyzes the Baeyer-Villiger conversion of progesterone into progesterone acetate using FAD as prosthetic group and NADPH as reducing cofactor. The enzyme shares high sequence similarity with well characterized Baeyer-Villiger monooxygenases, including phenylacetone monooxygenase and cyclohexanone monooxygenase. The comparative biochemical and structural analysis of STMO can be particularly insightful with regard to the understanding of the substrate-specificity properties of Baeyer-Villiger monooxygenases that are emerging as promising tools in biocatalytic applications and as targets for prodrug activation. The crystal structures of STMO in the native, NADP(+)-bound, and two mutant forms reveal structural details on this microbial steroid-degrading enzyme. The binding of the nicotinamide ring of NADP(+) is shifted with respect to the flavin compared with that observed in other monooxygenases of the same class. This finding fully supports the idea that NADP(H) adopts various positions during the catalytic cycle to perform its multiple functions in catalysis. The active site closely resembles that of phenylacetone monooxygenase. This observation led us to discover that STMO is capable of acting also on phenylacetone, which implies an impressive level of substrate promiscuity. The investigation of six mutants that target residues on the surface of the substrate-binding site reveals that enzymatic conversions of both progesterone and phenylacetone are largely insensitive to relatively drastic amino acid changes, with some mutants even displaying enhanced activity on progesterone. These features possibly reflect the fact that these enzymes are continuously evolving to acquire new activities, depending on the emerging availabilities of new compounds in the living environment.

Endoscopic endonasal anatomy of superior orbital fissure and orbital apex regions: critical considerations for clinical applications.

The superior orbital fissure is a critical three-dimensional space connecting the middle cranial fossa and the orbit. From an endoscopic viewpoint, only the medial aspect has a clinical significance. It presents a critical relationship with the lateral sellar compartment, the pterygopalatine fossa and the middle cranial fossa. The connective tissue layers and neural and vascular structures of this region are described. The role of Muller's muscle is confirmed, and the utility of the maxillary and optic strut is outlined. Muller's muscle extends for the whole length of the inferior orbital fissure, passes over the maxillary strut and enters the superior orbital fissure, representing a critical surgical landmark. Dividing the tendon between the medial and inferior rectus muscle allows the identification of the main trunk of the oculomotor nerve, and a little laterally, it is usually possible to visualize the first part of the ophthalmic artery. Based on a better knowledge of anatomy, we trust that this area could be readily addressed in clinical situations requiring an extended approach in proximity of the orbital apex.

A Deep Learning Approach for Diagnosis Support in Breast Cancer Microwave Tomography.

In this paper, a deep learning technique for tumor detection in a microwave tomography framework is proposed. Providing an easy and effective imaging technique for breast cancer detection is one of the main focuses for biomedical researchers. Recently, microwave tomography gained a great attention due to its ability to reconstruct the electric properties maps of the inner breast tissues, exploiting nonionizing radiations. A major drawback of tomographic approaches is related to the inversion algorithms, since the problem at hand is nonlinear and ill-posed. In recent decades, numerous studies focused on image reconstruction techniques, in same cases exploiting deep learning. In this study, deep learning is exploited to provide information about the presence of tumors based on tomographic measures. The proposed approach has been tested with a simulated database showing interesting performances, in particular for scenarios where the tumor mass is particularly small. In these cases, conventional reconstruction techniques fail in identifying the presence of suspicious tissues, while our approach correctly identifies these profiles as potentially pathological. Therefore, the proposed method can be exploited for early diagnosis purposes, where the mass to be detected can be particularly small.

Microwave Breast Sensing via Deep Learning for Tumor Spatial Localization by Probability Maps.

BACKGROUND: microwave imaging (MWI) has emerged as a promising modality for breast cancer screening, offering cost-effective, rapid, safe and comfortable exams. However, the practical application of MWI for tumor detection and localization is hampered by its inherent low resolution and low detection capability. METHODS: this study aims to generate an accurate tumor probability map directly from the scattering matrix. This direct conversion makes the probability map independent of specific image formation techniques and thus potentially complementary to any image formation technique. An approach based on a convolutional neural network (CNN) is used to convert the scattering matrix into a tumor probability map. The proposed deep learning model is trained using a large realistic numerical dataset of two-dimensional (2D) breast slices. The performance of the model is assessed through visual inspection and quantitative measures to assess the predictive quality at various levels of detail. RESULTS: the results demonstrate a remarkably high accuracy (0.9995) in classifying profiles as healthy or diseased, and exhibit the model's ability to accurately locate the core of a single tumor (within 0.9 cm for most cases). CONCLUSION: overall, this research demonstrates that an approach based on neural networks (NN) for direct conversion from scattering matrices to tumor probability maps holds promise in advancing state-of-the-art tumor detection algorithms in the MWI domain.

Cerebrospinal Fluid Leak During Stapes Surgery: The Importance of Temporal Bone CT Reconstructions in Oblique Anatomically Oriented Planes.

Stapes gusher is a massive flow of perilymph and cerebrospinal fluid leak that fills the middle ear immediately after surgical opening of the labyrinth, such as during stapedectomy. Stapes gusher usually occurs as the result of a congenital malformation that causes an abnormal communication between the perilymphatic space and the subarachnoid space involving the internal auditory canal or the cochlear duct. To date, the potential risk of stapes gusher cannot be assessed preoperatively, as there are not pathognomonic signs suggestive of this complication. However, high-resolution computed tomography scan (HRCT) of the temporal bone can provide information that may help recognizing patients at risk. Recently, an anatomic evaluation of the inner ear with oblique reformation at HRCT has been described. This reformation offers a new and more detailed topographic vision of temporal bone structures compared to the classic axial and coronal planes and may help identifying anatomical alterations otherwise not visible. In this article, we present a case of stapes gusher and the role of preoperative HRCT with oblique reformation in its prevention.

Structural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent N-hydroxylating monooxygenases.

SidA from the human pathogen Aspergillus fumigatus catalyzes the generation of N(5)-hydroxyornithine in the biosynthesis of siderophores, a reaction essential for virulence. The crystal structures of SidA in complex with ornithine and lysine reveal the geometry of the interactions among flavin, NADP(+), and the substrate amine group that underlie the hydroxylation reaction. The structural elucidation of the enzyme in complex with arginine provides insight into the role of electrostatics and hydrogen bonding in the mechanism of oxygen activation in this family of enzymes.

Ectopic intraorbital lacrimal ductal cyst: a case report.

Lacrimal ductal cysts are uncommon lesions that can occur everywhere in and around the eye. Ectopic location is very rare and can be misleading in the differential diagnosis of orbital masses. In this article we present the case of a 61-year-old-man with a medial intraconal ductal cyst of his right orbit. The patient was successfully treated with surgical excision.

An End-to-End Deep Learning Approach for Quantitative Microwave Breast Imaging in Real-Time Applications.

(1) Background: In this paper, an artificial neural network approach for effective and real-time quantitative microwave breast imaging is proposed. It proposes some numerical analyses for the optimization of the network architecture and the improvement of recovery performance and processing time in the microwave breast imaging framework, which represents a fundamental preliminary step for future diagnostic applications. (2) Methods: The methodological analysis of the proposed approach is based on two main aspects: firstly, the definition and generation of a proper database adopted for the training of the neural networks and, secondly, the design and analysis of different neural network architectures. (3) Results: The methodology was tested in noisy numerical scenarios with different values of SNR showing good robustness against noise. The results seem very promising in comparison with conventional nonlinear inverse scattering approaches from a qualitative as well as a quantitative point of view. (4) Conclusion: The use of quantitative microwave imaging and neural networks can represent a valid alternative to (or completion of) modern conventional medical imaging techniques since it is cheaper, safer, fast, and quantitative, thus suitable to assist medical decisions.

Hand Gesture Signatures Acquisition and Processing by Means of a Novel Ultrasound System.

Hand gestures represent a natural way to express concepts and emotions which are peculiar to each culture. Several studies exploit biometric traits, such as fingerprint, iris or face for subject identification purposes. Within this paper, a novel ultrasound system for person identification that exploits hand gestures is presented. The system works as a sonar, measuring the ultrasonic pressure waves scattered by the subject's hand, and analysing its Doppler information. Further, several transformations for obtaining time/frequency representations of the acquired signal are computed and a deep learning detector is implemented. The proposed system is cheap, reliable, contactless and can be easily integrated with other personal identification approaches allowing different security levels. The performances are evaluated via experimental tests carried out on a group of 25 volunteers. Results are encouraging, showing the promising potential of the system.