How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Management of patients with extensive locally advanced thyroid cancer: results of multimodal treatments.

PURPOSE: Surgery plays a key role in the treatment of thyroid cancer (TC) patients. Locally advanced cases, however, can require an extensive surgical approach with technical issues and a high risk of complications. In these cases, a multidisciplinary evaluation should be carried out to evaluate pros and cons. The aim of this study was to share our experience, as a multidisciplinary team, in the management of patients with locally advanced TC with a particularly extensive local disease, whose surgical approach could be challenging and part of a multimodal treatment. METHODS: We retrospectively evaluated clinical, surgical, and oncologic features of all patients with locally advanced TC who had undergone multidisciplinary surgery from January 2019 to June 2020. RESULTS: Six patients (two cases each of poorly differentiated, papillary, and medullary TC) were included. Four out of six were suffering from symptoms related to the advanced disease. At pre-surgical evaluation, a multidisciplinary team proposed extended surgery with radical intent via cervicotomy and sternotomy, considering other therapies not feasible or probably ineffective without it. No one passed away in intra- or perioperative time. At the end of follow-up (median 2.6 years), all patients presented a remission of symptoms due to the advanced disease, four patients were submitted to adjuvant therapies and only one patient died for a cause unrelated to the disease. CONCLUSION: This series of very advanced TCs shows the effectiveness of a surgery performed by a multidisciplinary team in controlling symptoms, allowing adjuvant therapies, and improving the survival of patients whose cases would otherwise be very difficult to manage.

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.

Production and characterization of 111Ag radioisotope for medical use in a TRIGA Mark II nuclear research reactor.

Radio Pharmaceutical Therapy (RPT) comes forth as a promising technique to treat a wide range of tumors while ensuring low collateral damage to nearby healthy tissues. This kind of cancer therapy exploits the radiation following the decay of a specific radionuclide to deliver a lethal dose to tumor tissues. In the framework of the ISOLPHARM project of INFN, 111Ag was recently proposed as a promising core of a therapeutic radiopharmaceutical. In this paper, the production of 111Ag via neutron activation of 110Pd-enriched samples inside a TRIGA Mark II nuclear research reactor is studied. The radioisotope production is modeled using two different Monte Carlo codes (MCNPX and PHITS) and a stand-alone inventory calculation code FISPACT-II, with different cross section data libraries. The whole process is simulated starting from an MCNP6-based reactor model producing the neutron spectrum and flux in the selected irradiation facility. Moreover, a cost-effective, robust and easy-to-use spectroscopic system, based on a Lanthanum Bromo-Chloride (LBC) inorganic scintillator, is designed and characterized, with the aim of using it, in the future, for the quality control of the ISOLPHARM irradiated targets at the SPES facility of the Legnaro National Laboratories of INFN. natPd and 110Pd-enriched samples are irradiated in the reactor main irradiation facility and spectroscopically characterized using the LBC-based setup and a multiple-fit analysis procedure. Experimental results are compared with theoretical predictions of the developed models, showing that inaccuracies in the available cross section libraries prevent an accurate reproduction of the generated radioisotope activities. Nevertheless, models are normalized to our experimental data allowing for a reliable planning of the 111Ag production in a TRIGA Mark II reactor.

Mycobacterium avium subsp. paratuberculosis and Crohn's disease: characterization of the interaction with different aspects of the disease.

Crohn's disease (CD) is a chronic granulomatous inflammatory bowel disease with no fully understood etiology and cure. Mycobacterium avium subspecies paratuberculosis (MAP), the etiologic agent of paratuberculosis, is also isolated from samples from human patients with CD. Paratuberculosis is characterized by persistent diarrhea and progressive weight loss and primarily affects ruminants, which eliminate the agent via feces and milk. The involvement of MAP in the pathogenesis of CD and other intestinal diseases is unclear. Thus, the present study aimed to analyze immunological, socioepidemiological, biochemical, and therapeutic variables that may be related to the occurrence of MAP in blood samples and CD patients. The sampling was random, and the population of origin was the patients from the Bowel Outpatient Clinic of the Alpha Institute of Gastroenterology (IAG), Hospital das Clínicas, Universidade Federal de Minas Gerais (HC-UFMG). Blood samples were collected from 20 patients with CD, eight with ulcerative rectocolitis (UCR), and 10 control patients without inflammatory bowel diseases. Samples were subjected to real-time PCR for detection of MAP DNA, oxidative stress analyses, and socioepidemiological variables. MAP was detected in 10 (26.3%) of the patients, seven (70%) were CD patients, 2 (20%) were URC patients, and one (10%) was a non-IBD patient. MAP was found more frequently among CD patients, but not restricted to CD patients. The presence of MAP in the blood of these patients occurred simultaneously with an inflammatory response with an increase in neutrophils and significant alterations in the production of antioxidant enzymes such as catalase and GST.

Neuromuscular and cardiac adverse events associated with immune checkpoint inhibitors: pooled analysis of individual cases from multiple institutions and literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple tumors, due to improved efficacy, quality of life, and safety. While most immune-related adverse events (irAEs) are mild and easily managed, in rare cases such events may be life-threatening, especially those affecting the neuromuscular and cardiac system. The management of neuromuscular/cardiac irAEs is not clear due to the lack of consistent data. Therefore, we carried out a pooled analysis of collected cases from selected Italian centers and individual data from published case reports and case series, in order to improve our understanding of these irAEs. PATIENTS AND METHODS: We collected retrospective data from patients treated in six Italian centers with ICIs (programmed cell death protein 1 or programmed death-ligand 1 and/or cytotoxic T-lymphocyte antigen 4 inhibitor) for any solid tumor who experienced neuromuscular and/or cardiovascular toxicity. Then, we carried out a search of case reports and series of neuromuscular/cardiac irAEs from ICIs with any solid tumor. RESULTS: This analysis includes cases from Italian institutions (n = 18) and the case reports identified in our systematic literature search (n = 120), for a total of 138 patients. Among these patients, 50 (36.2%) had complete resolution of their neuromuscular/cardiac irAEs, in 21 (15.2%) cases there was a clinical improvement with mild sequelae, and 53 (38.4%) patients died as a result of the irAEs. Factors significantly associated with worse outcomes were early irAE onset, within the first two cycles of ICI (Fisher P < 0.0001), clinical manifestation of both myositis and myocarditis when compared with patients who developed only myositis or myocarditis (chi-square P = 0.0045), and the development of arrhythmia (Fisher P = 0.0070). CONCLUSIONS: To the best of our knowledge, this is the largest collection of individual cases of immune-related myocarditis/myositis. Early irAE onset, concurrent development of myositis and myocarditis, as well as occurrence of arrhythmias are associated with worse outcomes and should encourage an aggressive immunomodulatory treatment.

A rare case of mycobacterial pseudoaneurysm of the superficial femoral artery.

OBJECTIVE: Extrapulmonary localization of tuberculosis accounts for about 15-20% of cases. Several cases of Mycobacterium tuberculosis with vascular involvement have been described, but only few cases for limb vessels. CASE REPORT: We report the case of a 33-year-old man from Gambia with a symptomatic pseudoaneurysm of the right superficial femoral artery. Total body positron emission tomography/computed tomography with [18F]FDG revealed an active infection. The patient underwent vascular reconstruction with a straight reversed vein graft. Molecular testing for Mycobacterium tuberculosis was non-diagnostic. Cultures of the pseudoaneurysm wall and thrombus removed during surgery grew Mycobacterium tuberculosis. CONCLUSIONS: The diagnosis of vascular tuberculosis infection due to Mycobacterium tuberculosis is a challenge. Epidemiology remains the primary criterion for maintaining a high index of suspicion.

Listeria abdominal endograft infection miming pseudoaneurysm treated with in-situ aortic reconstruction: a case report.

We report the case of a 72-year old man previously treated with an aortic endograft for an abdominal aortic aneurysm. After 3 years the patient developed a sepsis. Imaging and blood exams detected an endograft infection related to Listeria monocytogenes. Patients underwent endograft removal and in-situ aortic reconstruction with a cryopreserved allograft. A continuous antibacterial therapy has been established. One-month follow-up revealed the absence of clinically relevant infection with patency of the graft and absence of biochemical inflammatory markers.

CT scan structured report for the study of abdominal wall defects: a fast, easy and practical tool at the service of both surgeons and radiologist.

PURPOSE: The advantages offered by structured reporting have already been highlighted in the literature. However, there is still no evidence on the validity of this reporting method for the study of abdominal wall defects. This study aims to show the experience of the Trentino Hernia Team (THT) multidisciplinary group in the development and use of a structured CT scan report for the study of abdominal wall defects. METHODS: A regional multidisciplinary team (THT group) used a Delphi method to identify and select the most important CT scan parameters needed to describe and stage abdominal wall defects for correct preoperative planning. Based on the selected parameters, a CT scan structured report was worked out and collectively accepted. The first 20 structured reports obtained were individually tested for compilation speed and homogeneity of the data reported by five distinct radiologists. The reports were then evaluated by five different surgeons to test the simplicity of interpretation. RESULTS: We produced a model of a structured report for the study of the abdominal wall defects and tested it in our hospital network on the first 20 reports. The average completion time was 18 min (range 12-25). There was no heterogeneity among the reported data. The reports were analysed by five distinct surgeons to evaluate completeness and simplicity of interpretation. Each surgeon used a Likert scale from 0 to 5 to evaluate each report, producing average scores of 4.8 and 4.1 for completeness and comprehensibility respectively, with a mean combined total score of 8.9 out of 10. CONCLUSIONS: Our structured report represents a fundamental tool capable of providing the surgeon with all the measurements of the parameters necessary for correct preoperative planning. At the same time, it is of crucial help for the radiologists representing an easy and fast way to report all the needed parameters using the same standards.

Prognostic value of PET parameters in patients with pleomorphic lung cancer: Results from a single institution.

OBJECTIVES: Pleomorphic lung carcinoma (PLC) is a rare histotype of non-small cell lung cancer (NSCLC) characterized by aggressive clinical course, poor response to therapy and poor prognosis. Therefore, aim of our study is to analyze with 18F-FDG PET/CT a subset of patients affected by PLC to evaluate their metabolic characteristics in terms of SUVmax, MTV and TLG, in order to correlate them with overall survival (OS) and disease-free survival (DFS). MATERIAL AND METHODS: We retrospectively analyzed 49 consecutive patients with histologically defined PLC occurred to our Institution between 2003 and 2014. All patients underwent F18-FDG PET-CT before surgery and primary tumor was automatically segmented using an isocontour threshold method. SUV threshold for tumor segmentation was defined as the 41 % of lesion SUVmax. Total volume of the segmented VOI (MTV, centimeters cubed) and average SUV (SUVavg, grams per milliliter) in the segmented VOI were measured. RESULTS: In our population men were significantly more affected than women (42:7). According to Youden criteria, SUVmax, MTV41 and TLG41 best cut-off values to predict 2-year mortality were, 18.95, 27.89 and 290.45, respectively, with TLG41 showing best specificity (85 %) and positive predictive value (82.4 %). As concerning 2-year recurrence, SUVmax, MTV41 and TLG41 best cut-off values were 10.08, 27.89 and 134.85, with SUVmax showing best sensitivity (96.7 %) and negative predictive value (85.7 %). ROC curves confirmed that SUVmax, MTV41 and TLG41 were equally accurate to predict 2-year mortality and 2-year recurrence in our population. CONCLUSION: Metabolic biomarkers such as SUVmax, MTV and TLG can be used as a prognostic index for disease progression, recurrence and death in patients with PLC, independently from other clinical/pathological prognostic elements.

[Short version of the 2nd edition of the German-Austrian S3 guidelines "Cardiogenic shock complicating myocardial infarction-Diagnosis, monitoring and treatment"]. / Kurzversion der 2. Auflage der deutsch-österreichischen S3-Leitlinie "Infarkt-bedingter Kardiogener Schock ­ Diagnose, Monitoring und Therapie".

BACKGROUND: The present guidelines ( http://leitlinien.net ) focus exclusively on cardiogenic shock due to myocardial infarction (infarction-related cardiogenic shock, ICS). The cardiological/cardiac surgical and the intensive care medicine strategies dealt with in these guidelines are essential to the successful treatment and survival of patients with ICS; however, both European and American guidelines on myocardial infarction and heart failure and also position papers on cardiogenic shock focused mainly on cardiological aspects. METHODS: Evidence on the diagnosis, monitoring and treatment of ICS was collected and recommendations compiled in a nominal group process by delegates of the German Cardiac Society (DGK), the German Society for Medical Intensive Care Medicine and Emergency Medicine (DGIIN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG), the German Society for Anaesthesiology and Intensive Care Medicine (DGAI), the Austrian Society for Internal and General Intensive Care Medicine (ÖGIAIM), the Austrian Cardiology Society (ÖKG), the German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), under the auspices of the Working Group of the Association of Medical Scientific Societies in Germany (AWMF). If only poor evidence on ICS was available, general study results on intensive care patients were inspected and presented in order to enable analogue conclusions. RESULTS: A total of 95 recommendations, including 2 statements were compiled and based on these 7 algorithms with defined instructions on the course of treatment.

Predictive value of the sentinel lymph node procedure in the staging of non-metastatic colorectal cancer.

PURPOSE: Despite the recent growing interest of the scientific community, there is still no consensus on the actual applicability and effectiveness of sentinel lymph node (SL) procedure in colon cancers. This study aims to quantify feasibility, detection rate, negative predictive value, and accuracy of the SL identified with fluorescent dye in early colon cancers (ECC). METHODS: This study conducted a consecutive sampling of 95 patients with non-metastatic colorectal cancer who have been treated with laparoscopic colon resection and complete mesocolic excision after a 25-mg indocyanine green peritumoral laparoscopic injection and SL identification with a near-infrared camera. The SL was later isolated and sent to ultra-staging. RESULTS: Ninety-five patients with an average age of 71 (range 37-90) and a mean BMI of 25 (range 18-39) have been recruited. On the patient sample (92 Pts), an average of 1.49 SL (range 1-5) and a mean time of 4 min were identified. The detection rate was 96.8% and the negative predictive value and accuracy rates were 96.2% and 93.4%, respectively. CONCLUSIONS: Mapping the SL with fluorescent dye can play an important role in the treatment of colon cancers, particularly those at early stages, and can lead to ultra-conservative surgery.

Oxidative stress and Nrf2 expression in peripheral blood mononuclear cells derived from COPD patients: an observational longitudinal study.

BACKGROUND: A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression. Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time. METHODS: 33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects. A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months. RESULTS: In COPD, compared to no-COPD, we found a faster lung function decline at follow-up. Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced. Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD. The percent variation (Δ) of FEV1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001). Moreover ΔFEV1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = - 0.587, p < 0.01) and with baseline smoking history (r = - 0.39, p < 0.03). No correlation was found between ΔFEV1, ΔCRP and ΔWBCs. By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV1, ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV1, explaining 89.5% of its variance. CONCLUSIONS: Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression. Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease.

Generation of a neutralizing antibody against RD114-pseudotyped viral vectors.

The feline endogenous RD114 glycoprotein has proved to be an attractive envelope to pseudotype both retroviral and lentiviral vectors. As a surface protein, its detection on packaging cells as well as viral particles would be useful in different fields of its use. To address this, we generated a monoclonal antibody against RD114 by immunization of rats, termed 22F10. Once seroconversion was confirmed, purified 22F10 was cloned into murine Fc and characterized with a binding affinity of 10nM. The antibody was used to detect RD114 and its variant envelopes on different stable viral packaging cell lines (FLYRD18 and WinPac-RD). 22F10 was also shown to prevent the infections of different strains of RD-pseudotyped vectors but not related envelope glycoproteins by blocking cell surface receptor binding. We are the first to report the neutralization of viral particles by a monoclonal αRD114 antibody.

Genome size in three species of Glandularia and their hybrids / Tamaño del genoma en tres especies de Glandularia y sus híbridos

In this work the relationship between genome size of Glandularia species and the meiotic configurations found in their hybrids are discussed. Glandularia incisa (Hook.) Tronc., growing in two localities of Corrientes and Córdoba provinces, Argentina, with different ecological conditions, showed inter-population variability of the 2C-value. The DNA content found in the Corrientes locality (2.41 pg) was higher than that obtained in the Córdoba locality (2.09 pg) which has more stressful environmental conditions than the former. These values are statistically different from those that were found in Glandularia pulchella (Sweet) Tronc. from Corrientes (1.43 pg) and in Glandularia perakii Cov. et Schn from Córdoba (1.47 pg). The DNA content of the diploid F1 hybrids, G. pulchella × G. incisa and G. perakii × G. incisa, differed statistically from the DNA content of the parental species, being intermediate between them. Differences in the frequency of pairing of homoeologous chromosomes were observed in the hybrids; these differences cannot be explained by differences in genome size since hybrids with similar DNA content differ significantly in their meiotic behavior. On the other hand, the differences in the DNA content between the parental species justify the presence of a high frequency of heteromorphic open and closed bivalents and univalents with different size in the hybrids.

En el presente trabajo se discute la relación entre el tamaño del genoma en especies de Glandularia y las configuraciones meióticas encontradas en sus híbridos. El valor 2C mostró variabilidad interpoblacional en muestras de Glandularia incisa (Hook.) Tronc. coleccionadas en dos localidades con diferentes condiciones ecológicas (provincias de Corrientes y Córdoba, Argentina). El contenido de ADN encontrado en Corrientes (2,41 pg) fue mayor que el obtenido en Córdoba (2,09 pg) donde se registran condiciones ambientales más estresantes. Estos valores son estadísticamente diferentes de los determinados en Glandularia pulchella (Sweet) Tronc. de Corrientes (1.43 pg) y en Glandularia perakii Cov. et Schn de Córdoba (1.47 pg). El contenido de ADN de los híbridos diploides F1, G. pulchella × G. incisa y G. perakii × G. incisa, difirió estadísticamente del contenido de ADN registrado en las especies parentales siendo intermedio entre ellas. Las diferencias observadas en la frecuencia de apareamiento de cromosomas homeólogos no pueden explicarse por diferencias en el tamaño del genoma, ya que híbridos con un contenido de ADN similar difieren significativamente en su comportamiento meiótico. Sin embargo, la diferencia en el contenido de ADN entre las especies parentales explica la presencia de una alta frecuencia de bivalentes heteromórficos tanto abiertos como cerrados y univalentes con diferentes tamaños.

The use of only enamel matrix derivative allows outstanding regeneration results in periodontal intrabony defect treatment: a retrospective study.

Periodontal tissue regeneration depends on several biological, homeostatic and regulative variables that directly induce the clinical features. The aim of this study is to compare the clinical results obtained using the enamel matrix derivative peptide (EMP) compared to the less manageable association of EMP and bovine bone xenographic (BPBM) in the treatment of deep intraosseous defects. Ten healthy patients, suffering from moderate or severe chronic periodontitis, having at least two deep and narrow intrabony defects in the same dental arch and needing surgical treatment, were selected. The same patient was treated with the two different materials: EMP -TG1 in one defect and the association-TG2 in the other. Immediately before surgery (T0) and 12-month after (T2) the probing depth (PD) and gingival recession (GR) were registered at the experimental sites. No statistically significant differences were shown between TG1 and TG2 at T0 nor at T1 in term of PD and GR, while a statistically significant PD decrease was found both in TG1 and TG2 between T0 and T1 (p less than 0.05). GR increase resulted statistically significant in TG1 (p less than 0.05) but not in TG2 between T0 and T1 (p≥0.05). In this split-mouth retrospective study, both the treatments achieve favourable clinical results but the TG1 shows a significant increase in GR probably because EMP is not able to support the gingiva covering the intrabony defect. Therefore, the choice of the type of periodontal defect to be treated with EMP will be a therapeutic key-point.