Integrated endoscopic treatment of primitive unresectable tracheal tumor: the INTACT retrospective cohort study.

Background: Primitive tracheal tumors represent a rare entity whose management, when unresectable, remains challenging. Primary aim of this study was to explore the survival and the factors influencing prognosis of patients with unresectable primitive tracheal tumor undergoing multimodal treatment integrating interventional bronchoscopy and radiotherapy. Methods: This retrospective cohort study was conducted at the University Hospital of Modena (Italy) over a 12-year period (January 2010 to January 2022) analyzing patients with unresectable primary tracheal tumor receiving interventional bronchoscopy treatment followed by radiotherapy. Survival analysis was conducted for the whole population and according to histology, development of metastasis, stent placement and the onset of disease relapse. The raw and independent association between potential risk factor and 5-year mortality and the reported complications were investigated. Results: A total of 12 patients were included. Five-year survival rate was 42% with a median survival time of 26.7 (interquartile range, 4.1-82) months. Survivors showed a higher prevalence of cystic-adenoid histology (80% vs. 14%), while patients who were dead at 5 years were those with a more advanced T (prevalence of T2: 71% vs. 0%) and a lower response to first line treatment (57% vs. 0%). Treatment complications accounted for stent dislocation (33%) and the onset of granuloma (18%), while no major side effects were reported. The presence of cystic-adenoid histology resulted in significantly improved 5-year survival rate (80% vs. 14%). The onset of distal metastasis, the occurrence of disease relapse and the placement of tracheal stent did not result significantly associated with lower survival. Among analysed variables, only the presence of cystic-adenoid histology resulted independently associated with survival (odds ratio =0.1, P=0.04). Conclusions: Multimodal treatment including interventional bronchoscopy and associated radiotherapy for unresectable primary tracheal tumors seems not burdened by significant complications and may provide benefits in terms of survival for those patients with cystic-adenoid histology.

Surgical and radiological perspectives for the spinal accessory nerve passing through a fenestrated internal jugular vein: case series and literature review.

The preservation of the spinal accessory nerve represents a key goal in head and neck oncologic surgery during selective neck dissection. This study aims to illustrate the anatomical variants of the XI cranial nerve, delving into the relationship between the spinal nerve and the internal jugular vein, as well as the surgical implications. Two cases of patients who underwent oncologic surgery with neck dissection are described. Both cases found the spinal accessory nerve passing through the fenestration of the internal jugular vein. Alongside this case series, an independent literature review was conducted using the Medline and PubMed databases. In the majority of cases (67% - 96%), the spinal accessory nerve traces a lateral course to the internal jugular vein. Less frequently, the XI cranial nerve courses medial to the internal jugular vein. More rarely, as described in this case series, the nerve crosses through the fenestration of the vein (0.48% - 3.3%).

Tracing Allostery in the Spliceosome Ski2-like RNA Helicase Brr2.

RNA ATPases/helicases remodel substrate RNA-protein complexes in distinct ways. The different RNA ATPases/helicases, taking part in the spliceosome complex, reshape the RNA/RNA-protein contacts to enable premature-mRNA splicing. Among them, the bad response to refrigeration 2 (Brr2) helicase promotes U4/U6 small nuclear (sn)RNA unwinding via ATP-driven translocation of the U4 snRNA strand, thus playing a pivotal role during the activation, catalytic, and disassembly phases of splicing. The plastic Brr2 architecture consists of an enzymatically active N-terminal cassette (N-cassette) and a structurally similar but inactive C-terminal cassette (C-cassette). The C-cassette, along with other allosteric effectors and regulators, tightly and timely controls Brr2's function via an elusive mechanism. Here, microsecond-long molecular dynamics simulations, dynamical network theory, and community network analysis are combined to elucidate how allosteric effectors/regulators modulate the Brr2 function. We unexpectedly reveal that U4 snRNA itself acts as an allosteric regulator, amplifying the cross-talk of distal Brr2 domains and triggering a conformational reorganization of the protein. Our findings offer fundamental understanding into Brr2's mechanism of action and broaden our knowledge on the sophisticated regulatory mechanisms by which spliceosome ATPases/helicases control gene expression. This includes their allosteric regulation exerted by client RNA strands, a mechanism that may be broadly applicable to other RNA-dependent ATPases/helicases.

Lipoaspirate Injection in Relapsing Idiopathic Subglottic Stenosis: Preliminary Results.

OBJECTIVES: The management of idiopathic subglottic stenosis (iSGS) poses a clinical challenge due to high recurrence rates following both endoscopic and open approaches, often leading to tracheostomy. The activation of abnormal T-cells and cytokine pathways has been linked to iSGS pathogenesis. Autologous adipose tissue centrifugation yields lipoaspirate, offering optimal anti-inflammatory effects and biocompatibility widely utilized in various medical settings. This report presents the first 3 cases employing endoscopic dilation (ED) in combination with local lipoaspirate injection to address recurrent iSGS. METHODS: A prospective observational study was conducted, involving multidisciplinary evaluation by the Tracheal Team at the University of Modena. Patients meeting specific criteria were directed to undergo ED + lipoaspirate injection. RESULTS: Three patients fulfilled the inclusion criteria. The mean number of prior endoscopic procedures performed was 8. Endoscopic examination revealed 90% stenosis in patient A, 60% stenosis in patient B, and 60% stenosis in patient C. All patients presented inflammatory tissue or incipient granulations at the stenotic site, with an average time of 6 months between previous procedures. After 15 months, none of the patients required further procedures, and endoscopic examination revealed a significant reduction or disappearance of inflammatory tissue with a stable airway lumen. CONCLUSIONS: The observed results are encouraging in terms of reducing local inflammation and halting stenosis progression, especially in cases of short-term relapsing iSGS.

Post-Covid-19 Airway Stenosis: Tracheal Resection-Anastomosis Using The Tritube® Ventilation.

We present a video of a tracheal resection and anastomosis performed on a patient affected by A-shaped tracheal stenosis. The condition was a consequence of a percutaneous tracheostomy following a Sars-Cov2 infection. Airways management during the surgery was obtained with the Tritube®, an innovative device with a very small lumen that combines stable lung parameters and good visualization of surgical field. Laryngoscope, 134:897-900, 2024.

Endoscopic Temporalis Tendon Extension (ETTE).

Many techniques have been proposed to restore facial symmetry in facial nerve palsies. This study presents our surgical approach called Endoscopic Temporalis Tendon Extension (ETTE). After nasotracheal intubation, a 4 cm skin incision is made at the nasolabial fold. Under endoscopic view, the medial face of the masseter muscle is detached from the mandibular ramus. The coronoid process is then sectioned by Piezosurgery®. Finally, a fascia lata graft is suspended between the temporalis tendon and the orbicularis oris. ETTE is a mixed technique, with a static suspension component and a dynamic contraction one. The preservation of the temporalis muscle insertion in temporal fossa allows for an optimal contraction. A fascia lata graft is necessary for reasons of length. The scar produced by the nasolabial incision allows to recreate the missing nasolabial fold. The endoscopic assistance provides greater precision during the procedure and entails a shorter learning curve.

The transcervical-transparotid corridor for management of parapharyngeal space neoplasms: strengths and limits in a bi-institutional retrospective series.

BACKGROUND AND PURPOSE: Parapharyngeal space (PPS) neoplasms represent 1% of all head and neck tumors and are mostly benign. Surgery is the mainstay of treatment and the transcervical-transparotid (TC-TP) corridor still represents the workhorse for adequate PPS exposure. Our series investigates strengths and limits of this approach on a multi-institutional basis. METHODS: We reviewed consecutive patients submitted to PPS surgery via TC-TP route between 2010 and 2020. Hospital stay, early and long-term complications, and disease status were assessed. RESULTS: One hundred and twenty nine patients were enrolled. Most tumors were benign (79.8%) and involved the prestyloid space (83.7%); the median largest diameter was 4.0 cm. The TC-TP corridor was used in 70.5% of patients, while a pure TC route in about a quarter of cases. Early postoperative VII CN palsy was evident in 32.3% of patients, while X CN deficit in 9.4%. The long-term morbidity rate was 34.1%, with persistent CN impairment detectable in 26.4% of patients: carotid space location, lesion diameter and malignant histology were the main independent predictors of morbidity. A recurrence occurred in 12 patients (9.4%). CONCLUSIONS: The TC-TP corridor represents the benchmark for surgical management of most of PPS neoplasms, though substantial morbidity can still be expected.

Non-invasive brain stimulation for patients and healthy subjects: Current challenges and future perspectives.

Non-invasive brain stimulation (NIBS) techniques have a rich historical background, yet their utilization has witnessed significant growth only recently. These techniques encompass transcranial electrical stimulation and transcranial magnetic stimulation, which were initially employed in neuroscience to explore the intricate relationship between the brain and behaviour. However, they are increasingly finding application in research contexts as a means to address various neurological, psychiatric, and neurodegenerative disorders. This article aims to fulfill two primary objectives. Firstly, it seeks to showcase the current state of the art in the clinical application of NIBS, highlighting how it can improve and complement existing treatments. Secondly, it provides a comprehensive overview of the utilization of NIBS in augmenting the brain function of healthy individuals, thereby enhancing their performance. Furthermore, the article delves into the points of convergence and divergence between these two techniques. It also addresses the existing challenges and future prospects associated with NIBS from ethical and research standpoints.

Molecular Biology and Therapeutic Targets of Primitive Tracheal Tumors: Focus on Tumors Derived by Salivary Glands and Squamous Cell Carcinoma.

Primary tracheal tumors are rare, constituting approximately 0.1-0.4% of malignant diseases. Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) account for about two-thirds of these tumors. Despite most primary tracheal cancers being eligible for surgery and/or radiotherapy, unresectable, recurrent and metastatic tumors may require systemic treatments. Unfortunately, the poor response to available chemotherapy as well as the lack of other real therapeutic alternatives affects the quality of life and outcome of patients suffering from more advanced disease. In this condition, target therapy against driver mutations could constitute an alternative to chemotherapy, and may help in disease control. The past two decades have seen extraordinary progress in developing novel target treatment options, shifting the treatment paradigm for several cancers such as lung cancer. The improvement of knowledge regarding the genetic and biological alterations, of major primary tracheal tumors, has opened up new treatment perspectives, suggesting the possible role of biological targeted therapies for the treatment of these rare tumors. The purpose of this review is to outline the state of knowledge regarding the molecular biology, and the preliminary data on target treatments of the main primary tracheal tumors, focusing on salivary-gland-derived cancers and squamous cell carcinoma.

Impact of lymph node ratio and number of lymph node metastases on survival and recurrence in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

Case report: Endoscopic closure with double stenting and autologous fascia lata graft of large tracheo-esophageal fistula.

Introduction: Radiotherapy and esophageal stenting are usually employed to manage esophageal localization of distant cancer. However, they are also related to the occurrence of an increased risk of tracheoesophageal fistula. Tracheoesophageal fistula management in these patients involves dealing with poor general conditions and short-term prognosis. This paper presents the first case in literature of bronchoscopic fistula closure through an autologous fascia lata graft placement between two stents. Case report and aim: A 67-years-old male patient was diagnosed with pulmonary squamous cell carcinoma in the inferior lobe of the left lung with mediastinal lymph node metastasis. After a multidisciplinary discussion, bronchoscopic repair of tracheoesophageal fistula with autologous fascia lata was decided without the removal of the esophageal stent due to the high risk on the esophagus possibly related to such a procedure. Oral feeding was progressively introduced without the development of aspiration symptoms. Videofluoroscopy and esophagogastroduodenoscopy were performed at 7 months showing no signs of tracheoesophageal fistula patency. Conclusion: This technique might represent a low risks viable option for patients unsuitable for open surgical approaches.

Oropharyngeal squamous cell carcinoma: Prognostic factors for development of distant metastases and oncological outcomes.

BACKGROUND: Distant metastasis (DM) development in Oropharyngeal Squamous Cell Carcinoma (OPSCC) represents an important prognostic factor. The identification of a phenotype of metastatic patients may better define therapeutic and follow-up programs. METHODS: We included 408 patients with OPSCC, non-metastatic at the time of diagnosis, and treated with curative intent. The Overall Survival (OS) analyses were performed and the impact of developing DM on survival was analyzed through Cox proportional-hazard regression model. RESULTS: 57 (14%) patients develop DM. 302 (74%) were p16+ OPSCC and 35 of them experienced DM. Advanced clinical stage, smoking, p16-status, response to primary treatment, and loco-regional relapse influence the DM rate. Only in the p16+ group, DM onset results in a greater impact on OS (p < 0.0001). Lung metastases have a better OS compared to non-pulmonary ones (p = 0.049). CONCLUSION: This retrospective study shows a possible stratification of OPSCC patients based on the risk of the development of DMs.

Paraglottic Space Invasion in Glottic Laryngeal Cancer: A Clinical-Pathological Study.

OBJECTIVE: This study aims to prospectively compare endoscopic, radiological, and pathological features of a cohort of patients with glottic laryngeal squamous cell carcinoma (LSCC) undergoing open partial horizontal laryngectomy (OPHL) type II/III or total laryngectomy to better understand the reliability of preoperative endoscopy and computed tomography (CT) to predict the inferior paraglottic space (iPGS) involvement. METHODS: We prospectively compared the endoscopic, radiological, and pathological findings in patients with glottic LSCC who underwent OPHL II/III, or total laryngectomy. RESULTS: Endoscopy achieved a diagnostic accuracy of 87.2% for the anterior iPGS (iPGSa) and 86.1% for the posterior iPGS (iPGSp). There was no statistically significant difference in terms of histopathologic iPGSa involvement between reduced (85%-17/20 pts) and absent (92%-24/26 pts) vocal cord mobility (p = 0.39). CT alone did not improve the diagnostic performance of the endoscopy, reaching a diagnostic accuracy of 62.9% and 73.7% for the iPGSa and iPGSp, respectively. When endoscopy and CT were combined, the diagnostic performance improved for the iPGSp, achieving a sensitivity (Se), specificity (Spe), positive predictive value (PPV), and negative predictive value (NPV) of 100%, 89.8%, 68.7%, and 100%, respectively. On the contrary, the combination of CT and endoscopy improved only the Se and NPV for the iPGSa with respect to the sole endoscopic assessment. CONCLUSIONS: Whenever motility impairment is present, a histopathologic invasion of the iPGS should be suspected. Endoscopic assessment of laryngeal motility achieved a satisfactory value of Se, Spe, PPV, and NPV in predicting the involvement of the iPGS. CT scan is still the mainstay imaging technique in the clinical staging of patients with LSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1184-1190, 2023.

Are Neural Network Potentials Trained on Liquid States Transferable to Crystal Nucleation? A Test on Ice Nucleation in the mW Water Model.

Neural network potentials (NNPs) are increasingly being used to study processes that happen on long time scales. A typical example is crystal nucleation, which rate is controlled by the occurrence of a rare fluctuation, i.e., the appearance of the critical nucleus. Because the properties of this nucleus are far from those of the bulk crystal, it is yet unclear whether NN potentials trained on equilibrium liquid states can accurately describe nucleation processes. So far, nucleation studies on NNPs have been limited to ab initio models whose nucleation properties are unknown, preventing an accurate comparison. Here we train a NN potential on the mW model of water─a classical three-body potential whose nucleation time scale is accessible in standard simulations. We show that a NNP trained only on a small number of liquid state points can reproduce with great accuracy the nucleation rates and free energy barriers of the original model, computed from both spontaneous and biased trajectories, strongly supporting the use of NNPs to study nucleation events.

Oncological and Functional Outcomes for Horizontal Glottectomy: A Systematic Review.

Horizontal glottectomy (HG) is a particular type of partial laryngectomy indicated for exclusive glottic tumor with anterior commissure involvement. The purpose of this study is to systematically review the literature about functional and oncological outcome of HG. This systematic review adhered to the recommendations of the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-analysis) 2009 guidelines. Articles mentioning patients undergoing HG for laryngeal squamous cell carcinoma were included. A total of 14 articles were selected and reviewed from 19 identified. The whole study population consisted of 420 patients who underwent HG. Three hundred and thirty-nine patients out of 359 were staged as T1. The range of post-operative follow-up was 5 months to 10 years. Fifty-five recurrences were experienced, being local, regional and distant in 35, 12 and 8 patients, respectively. Laryngeal preservation rate was 93.6%. Nasogastrict tube was removed on average after 10.1 days. The tracheostomy was maintained for 11.3 days. Mean hospitalization lasted for 11.7 days. According to the results of this systematic review, HG is an oncologically safe surgical option for T1a-T1b glottic tumors with oncological outcomes comparable to other treatment. HG could be a good therapeutical choice whenever poor laryngeal exposure and/or patient's refusal of radiotherapy are encountered, or when patient's medical history represents a contraindication for radiation therapy.

A neural network potential with self-trained atomic fingerprints: A test with the mW water potential.

We present a neural network (NN) potential based on a new set of atomic fingerprints built upon two- and three-body contributions that probe distances and local orientational order, respectively. Compared with the existing NN potentials, the atomic fingerprints depend on a small set of tunable parameters that are trained together with the NN weights. In addition to simplifying the selection of the atomic fingerprints, this strategy can also considerably increase the overall accuracy of the network representation. To tackle the simultaneous training of the atomic fingerprint parameters and NN weights, we adopt an annealing protocol that progressively cycles the learning rate, significantly improving the accuracy of the NN potential. We test the performance of the network potential against the mW model of water, which is a classical three-body potential that well captures the anomalies of the liquid phase. Trained on just three state points, the NN potential is able to reproduce the mW model in a very wide range of densities and temperatures, from negative pressures to several GPa, capturing the transition from an open random tetrahedral network to a dense interpenetrated network. The NN potential also reproduces very well properties for which it was not explicitly trained, such as dynamical properties and the structure of the stable crystalline phases of mW.

The role of adjuvant therapy in pT4N0 laryngectomized patients: Multicentric observational study.

BACKGROUND: To retrospectively evaluate oncological outcomes in two groups of patients with pT4aN0 glottic SCC treated with total laryngectomy (TL) and neck dissection (ND) who underwent postoperative radiotherapy or exclusive clinical and radiological follow-up. METHODS: It includes patients with pT4N0 glottic SCC who underwent TL and unilateral or bilateral ND with or without PORT. Divided in two comparison groups: the first group underwent adjuvant RT (TL-PORT); the second group referred to clinical and radiological follow-up (TL). RESULTS: PORT was associated with a better OS while no differences were found in terms of DSS. A better local control is achieved when PORT is administered while no differences in terms of regional and distant control rates were found. Bilateral ND positively impacts on the regional control while the PNI negatively impact the regional control. CONCLUSIONS: A tailored PORT protocol might be considered for pT4N0 glottic SCC treated with TL and ND, both considering the ND's extent and presence of PNI.

Low-Temperature Stability and Sensing Performance of Mid-Infrared Bloch Surface Waves on a One-Dimensional Photonic Crystal.

The growing need for new and reliable surface sensing methods is arousing interest in the electromagnetic excitations of ultrathin films, i.e., to generate electromagnetic field distributions that resonantly interact with the most significant quasi-particles of condensed matter. In such a context, Bloch surface waves turned out to be a valid alternative to surface plasmon polaritons to implement high-sensitivity sensors in the visible spectral range. Only in the last few years, however, has their use been extended to infrared wavelengths, which represent a powerful tool for detecting and recognizing molecular species and crystalline structures. In this work, we demonstrate, by means of high-resolution reflectivity measurements, that a one-dimensional photonic crystal can sustain Bloch surface waves in the infrared spectral range from room temperature down to 10 K. To the best of our knowledge, this is the first demonstration of infrared Bloch surface waves at cryogenic temperatures. Furthermore, by exploiting the enhancement of the surface state and the high brilliance of infrared synchrotron radiation, we demonstrate that the proposed BSW-based sensor has a sensitivity on the order of 2.9 cm-1 for each nanometer-thick ice layer grown on its surface below 150 K. In conclusion, we believe that Bloch surface wave-based sensors are a valid new class of surface mode-based sensors for applications in materials science.

Microsurgical training using an ex-vivo model: microscope vs 3D exoscope.

Objective: The aim of this study is to evaluate the feasibility of the 3D exoscope in a microvascular anastomosis training setting and compare it with the gold-standard technique using the operating microscope (OM). Methods: Participants were recruited among otorhinolaryngology head and neck surgery (OHNS) residents of two tertiary care hospitals. Trainees were asked to complete 4 microvascular end-to-end anastomoses on chicken thighs with the OM and VITOM 3D exoscope. The performances were scored by experienced microvascular surgeons; an objective evaluation of the anastomosis and a subjective assessment of the workload were conducted. Results: 8 OHNS residents were recruited. Considering the amount of time needed to complete (TTC) the anastomosis, an improvement was shown by all the participants throughout the training program. The objective evaluation of the anastomosis did not show a significant difference. No significant differences were found by analyzing the subjective workload with the different tools. Conclusions: This article represents the first attempt to compare the use of the OM and the 3D exoscope during training for microsurgery. The results of our study demonstrate the noninferiority of microsurgical training obtained using the 3D exoscope compared to that offered by the OM.

Stenting versus balloon dilatation in patients with tracheal benign stenosis: The STROBE trial.

Background: It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods: A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be "stabilized" (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long-term (2 years) following the endoscopic procedure. Results: Sixty-six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan-Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5-9.8], p = .01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p = .01). Conclusions: Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3.