Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

Analytical Control of Homoclinic Bifurcation of the Hilltop Saddle in a Noncontact Atomic Force Microcantilever

AbstractA control procedure of global dynamics is applied to a reduced order model of noncontact AFM with the aim to shift the homoclinic bifurcation involving the system hilltop saddle. The method consists of adding to the system harmonic excitation controlling superharmonics to be properly identified by solving an optimization problem. The analytical bifurcation threshold is determined through the asymptotic Melnikov method, for the reference system and for the controlled system. The practical effect of the control as regards possibly increasing the system overall robustness by shifting the start of the erosion of the safe basin is then numerically investigated by means of a dynamical integrity analysis based on the evolution of basins of attraction

Cross-Cultural Validation of the Short Version of the Questionnaire of Olfactory Disorders-Negative Statements into Italian: Towards Personalized Patient Care

Given the high burden of olfactory dysfunction worldwide, recently increased due to the COVID-19 pandemic, it is mandatory to adopt a specific questionnaire to assess the impact of olfactory impairment on quality of life, to be used in clinical practice. The aim of this study is to adapt and validate the short version of the Questionnaire of Olfactory Disorders-Negative Statements (svQOD-NS) for Italian. In the pilot phase, the Italian version of the questionnaire (ITA-svQOD-NS) was produced following recommended guidelines. It was then given to 50 healthy subjects and 50 patients (affected by either nasal polyposis or septal deviation), and results were compared to those of other widely used questionnaires. Test-retest reliability was assessed on a sample of 25 patients. All 50 patients repeated the questionnaires at one and nine months after surgery. The internal consistency of ITA-svQOD-NS measured with Cronbach alpha was excellent (alpha = 0.92). The intraclass correlation coefficient for test-retest reliability was also optimal (0.93; 95%CI: 0.90-0.96). Concurrent validity tested with the Pearson coefficient was significant with all other tests administered; also, concerning responsiveness, statistically significant differences were obtained between pre- and post-operative conditions. ITA-svQOD-NS showed high internal consistency, test-retest reliability, and significant correlation with all most-used clinical questionnaires; thus, it can be efficiently applied to assess olfaction-related QoL in the Italian population

Assessment of Electromagnetic Absorption of Ice From Ice Core Measurements

DOME C is located on the East Antarctic Plateau at an altitude of 3233 m above sea level and is the site of the Italian–French base, i.e., the Concordia Station ( 123∘20′ E, 75∘06′ S). It has become an important location for several scientific research studies, including astrophysics, geophysics, glaciology, and climatology, due to the perceived long-term stability and thickness of ice at this location [1], [5], [18], [24]. During the site selection and follow up of the EPICA Dome C coring project, which ultimately provided more than 800 000 years of palaeoclimatic series distributed along 3270 m [6], numerous radio-echo sounding (RES) surveys were undertaken to improve core positioning and subsequently to better leverage data and logistical infrastructures from the coring effort. These studies were conducted at very different scales over the Dome C region and revealed important information about the bedrock physiography and its physical conditions [2]– [4], [8], [9], [19], [20], [30], [31]. This study builds upon these efforts using data from two recently acquired ground-based surveys collected during 2009 and 2011 in a very small area (2.5 × 2.0 km) in the immediate proximity of the EPICA drilling site, to test advances in the acquisition and digitization technology and resolve the basal environment to unprecedented detail.Published4758 - 47635A. Paleoclima e ricerche polariJCR Journa

Elective Neck Dissection during Salvage Total Laryngectomy: Personal Experience

The role of elective neck dissection during salvage surgery in patients with a clinically negative neck (cN0) is still discussed. The main objective of this work was to estimate the prevalence and predictive factors of occult neck nodes metastasis; we therefore aimed to evaluate the survival rate and the main oncologic outcomes of cN0 patients who underwent salvage total laryngectomy and elective bilateral neck dissection. In this retrospective observational study, we enrolled 80 cN0 patients affected by recurrent laryngeal cancer and who underwent salvage total laryngectomy and bilateral selective elective neck dissection. Several parameters were collected in order to find prognostic factors; finally, postoperative complications were reviewed and survival analysis was performed. Occult lymph node metastases were reported in 18 out of 80 patients (22.5%). Significant statistical correlation between lymphovascular invasion (p = 0.007), perineural invasion (p = 0.025) and occult nodal metastasis was found. Other variables (glottic subsite of recurrence, clinical T, pathological T, previous chemotherapy) were not significantly predictive of occult nodal metastasis. The 5-year OS, DSS, and RFS were 50.4%, 64.7%, and 63.4%, respectively. In conclusion, our single-institution data on a large cohort of patients, suggest performing routinely elective selective bilateral neck dissection during salvage total laryngectomy in cN0 patients due to the biological attitude of the tumor to spread to cervical nodes, considering an acceptable complications rate

Factors Influencing Personalized Management of Vestibular Schwannoma: A Systematic Review

Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or microsurgical resection or wait and scan (WS). The aim of the review was to clarify which patient and tumor parameters may lead to different therapeutic choices, with a view to a personalized VS approach. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between February and March 2022. The authors defined six parameters that seemed to influence decision-making in VS management: 1-incidental VS; 2-tumor size; 3-tumor regrowth after sRT; 4-subtotal resection; 5-patients’ age; 6-symptoms. The initial search yielded 3532 articles, and finally, 812 articles were included. Through a qualitative synthesis of the included studies, management strategies were evaluated and discussed. An individualized proposal of procedures is preferable as compared to a single gold-standard approach in VS decision-making. The most significant factors that need to be considered when dealing with a VS diagnosis are age, tumor size and hearing preservation issues

Clinical Markers of Need for Surgery in Orbital Complication of Acute Rhinosinusitis in Children: Overview and Systematic Review

Background: Although they can occur at all ages, orbital (OC) and periorbital cellulitis (POC) prevail in the pediatric population. Acute rhinosinusitis (ARS) is the most frequent predisposing factor of OC. Recent literature has suggested a medical management approach for OC and POC, with surgery reserved only for more severe cases. However, there is still a lack of consensus on the clinical markers of a need for surgery. The aim of this systematic review was to identify clinical markers of a need for surgery in children with OC. Our systematic review, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process, yielded 1289 articles finally screened. This resulted in 31 full texts that were included in a qualitative analysis. The results of this review suggest that in children aged over 9 years, large subperiosteal orbital abscesses (SPOAs), impaired vision, ophthalmoplegia, proptosis, elevated C-reactive protein (CRP) and absolute neutrophil counts (ANC), hemodynamic compromise, no clinical improvement after 48/72 h of antibiotic therapy, and a Chandler III score or higher are clinical markers of the need for surgery. However, most of the studies are observational and retrospective, and further studies are needed to identify reliable and repeatable clinical markers of the need for surgery

Clinical Markers of Need for Surgery in Orbital Complication of Acute Rhinosinusitis in Children: Overview and Systematic Review

Background: Although they can occur at all ages, orbital (OC) and periorbital cellulitis (POC) prevail in the pediatric population. Acute rhinosinusitis (ARS) is the most frequent predisposing factor of OC. Recent literature has suggested a medical management approach for OC and POC, with surgery reserved only for more severe cases. However, there is still a lack of consensus on the clinical markers of a need for surgery. The aim of this systematic review was to identify clinical markers of a need for surgery in children with OC. Our systematic review, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process, yielded 1289 articles finally screened. This resulted in 31 full texts that were included in a qualitative analysis. The results of this review suggest that in children aged over 9 years, large subperiosteal orbital abscesses (SPOAs), impaired vision, ophthalmoplegia, proptosis, elevated C-reactive protein (CRP) and absolute neutrophil counts (ANC), hemodynamic compromise, no clinical improvement after 48/72 h of antibiotic therapy, and a Chandler III score or higher are clinical markers of the need for surgery. However, most of the studies are observational and retrospective, and further studies are needed to identify reliable and repeatable clinical markers of the need for surgery