Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2.

The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (Bm) cell subsets, including CD21+ resting, CD21-CD27+ activated and CD21-CD27- Bm cells. The interrelatedness between these Bm cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specific Bm cell clones showed plasticity upon antigen rechallenge in previously exposed individuals. CD21- Bm cells were the predominant subsets during acute infection and early after severe acute respiratory syndrome coronavirus 2-specific immunization. At months 6 and 12 post-infection, CD21+ resting Bm cells were the major Bm cell subset in the circulation and were also detected in peripheral lymphoid organs, where they carried tissue residency markers. Tracking of individual B cell clones by B cell receptor sequencing revealed that previously fated Bm cell clones could redifferentiate upon antigen rechallenge into other Bm cell subsets, including CD21-CD27- Bm cells, demonstrating that single Bm cell clones can adopt functionally different trajectories.

Detection of Scedosporium spp.: Colonizer or pathogen? A retrospective analysis of clinical significance and management in a large tertiary center.

Infections with Scedosporium spp. are emerging in the past two decades and are associated with a high mortality rate. Microbiological detection can be associated with either colonization or infection. Evolution from colonization into infection is difficult to predict and clinical management upon microbiological detection is complex. Microbiological samples from 2015 to 2021 were retrospectively analyzed in a single tertiary care center. Classification into colonization or infection was performed upon first microbiological detection. Clinical evolution was observed until July 2023. Further diagnostic procedures after initial detection were analyzed. Among 38 patients with microbiological detection of Scedosporium spp., 10 were diagnosed with an infection at the initial detection and two progressed from colonization to infection during the observation time. The main sites of infection were lung (5/12; 41.6%) followed by ocular sites (4/12; 33.3%). Imaging, bronchoscopy or biopsies upon detection were performed in a minority of patients. Overall mortality rate was similar in both groups initially classified as colonization or infection [30.7% and 33.3%, respectively (P = 1.0)]. In all patients where surgical debridement of site of infection was performed (5/12; 42%); no death was observed. Although death occurred more often in the group without eradication (3/4; 75%) compared with the group with successful eradication (1/8; 12.5%), statistical significance could not be reached (P = 0.053). As therapeutic management directly impacts patients' outcome, a multidisciplinary approach upon microbiological detection of Scedosporium spp. should be encouraged. Data from larger cohorts are warranted in order to analyze contributing factors favoring the evolution from colonization into infection.

Scedosporium is an environmental mould with a varied clinical relevance, as described in this cohort from a tertiary centre. Its microbiological detection represents a colonization or infection. An interdisciplinary approach is crucial for an optimal diagnostic strategy and patient outcome.

Predicting dupilumab treatment outcome in patients with primary diffuse type 2 chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis with a type 2 inflammatory pattern (T2CRS) is believed to be restricted to the nose and sinuses and associated with polyps, without clear serologic markers. Dupilumab is a promising new therapy in difficult to treat T2CRS. No factors are known to predict dupilumab treatment outcome. METHODS: Patients undergoing dupilumab treatment were assessed clinically to report ultra-short- and short-term outcome up to 90 days. Serum samples were taken on day 0 and 30 days of treatment, and proteomic analyses were performed using Olink®. The results were compared with healthy controls (HC). The aim was to identify clinical and serological markers associated with a treatment response to dupilumab. Confirmation of predictive parameters was evaluated in a prospective cohort of 20 T2CRS patients. RESULTS: Thirty patients were included, 80% of which were treatment responders. SinoNasalOutcomeTest-20 (SNOT-20) scores and the total nasal polyp score improved significantly (p < .05) on Day 7. An improvement of 2.5 points at the first visit was associated with a favorable outcome with a sensitivity of 86%. Proteomic analyses revealed significant changes compared with HC. Furthermore, we could identify OPG in the serum of dupilumab-treated patients that may serve as a predictor of the clinical outcome of dupilumab treatment. The predictive value of OPG was confirmed in the second cohort. CONCLUSION: Clinical response after 1 week of treatment with dupilumab is highly associated with a favorable outcome. High sensitivity proteomic analyses can identify T2CRS-specific dysregulated proteins in serum. Serum OPG may serve as a predictor for dupilumab treatment outcome before the initiation of any therapy.

Dupilumab-induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis.

BACKGROUND: Dupilumab, a monoclonal anti-IL-4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy. This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy. METHODS: Patients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start. Sino-Nasal-Outcome-Test Score (SNOT-22), Total Nasal Polyp Score (TNPS), and blood samples were collected. Cytokine measurements and proteomics analysis were conducted. Flow cytometry analysis measured receptor expression on eosinophils. RESULTS: Sixty-eighty patients were included. Baseline eosinophilia ≥0.3G/L was observed in 63.2% of patients, and in 30.9% of patients, eosinophils increased by ≥0.5G/L under dupilumab. Subjects with eosinophilia ≥0.3G/L at baseline had the best SNOT-22 mean change compared to no eosinophilia. Eosinophil elevation during dupilumab therapy had no impact on clinical scores. The eosinophil adhesion molecule VCAM-1 decreased significantly during therapy in all patients. The chemokine receptor CXCR4 was significantly down- and IL-4 upregulated in subjects with eosinophil increase. CONCLUSION: Our findings suggest that increased eosinophils in type 2 CRS are associated with a good clinical response to dupilumab. Patients with elevated IL-4 at baseline developed dupilumab-induced transient eosinophilia. We identified the downregulation of VCAM-1 and surface markers CD49d and CXCR4 on eosinophils as possible explanations of dupilumab-induced eosinophilia.

Atherosclerosis of the iliac arteries for the prediction of erectile dysfunction and epistaxis in men undergoing abdominal CT scan.

BACKGROUND: To investigate the association between erectile dysfunction (ED) as well as epistaxis (ES) in relation to the extent of iliac atherosclerosis. METHODS: In this retrospective cross-sectional study, all consecutive male patients treated at our institution from 01/2016 to 12/2020 undergoing abdominal CT scan were evaluated. Patients (n = 1272) were invited by mail to participate in the study in returning two questionnaires for the evaluation of ED (IIEF-5) and ES. Patients who returned filled-in questionnaires within a 3-month deadline were included in the study. The extent of atherosclerosis in the common iliac artery (CIA) and the internal iliac artery (IIA) was assessed by calcium scoring on unenhanced CT. Stratification of results was performed according to reported IIEF-5 scores and consequential ED groups. RESULTS: In total, 437 patients (34.4% of contacted) met the inclusion criteria. Forty-two patients did not fulfill predefined age requirements (< 75 years) and 120 patients had to be excluded as calcium scoring on nonenhanced CT was not feasible. Finally, 275 patients were included in the analysis and stratified into groups of "no-mild" (n = 146) and "moderate-severe" (n = 129) ED. The calcium score (r=-0.28, p < 0.001) and the number of atherosclerotic lesions (r=-0.32, p < 0.001) in the CIA + IIA showed a significant negative correlation to the IIEF-5 score, respectively. Patients differed significantly in CIA + IIA calcium score (difference: 167.4, p < 0.001) and number of atherosclerotic lesions (difference: 5.00, p < 0.001) when belonging to the "no-mild" vs. "moderate-severe" ED group, respectively. A multivariable regression model, after adjusting for relevant baseline characteristics, showed that the number of atherosclerotic CIA + IIA lesions was an independent predictor of ED (OR = 1.05, p = 0.036), whereas CIA + IIA calcium score was not (OR = 1.00031, p = 0.20). No relevant correlation was found between ES episodes and IIEF-5 scores (r=-0.069, p = 0.25), CIA + IIA calcium score (r=-0.10, p = 0.87) or number of atherosclerotic CIA + IIA lesions (r=-0.032, p = 0.60), respectively. CONCLUSIONS: The number of atherosclerotic lesions in the iliac arteries on nonenhanced abdominal CT scans is associated with the severity of ED. This may be used to identify subclinical cardiovascular disease and to quantify the risk for cardiovascular hazards in the future. TRIAL REGISTRATION: BASEC-Nr. 2020 - 01637.

Impact of extended sinus surgery on allograft infection, allograft function and overall survival in cystic fibrosis lung transplant recipients.

BACKGROUND: Studies investigating the impact of sinus surgery for cystic fibrosis (CF) patients performed early after lung transplantation (Ltx) are scarce. Recent studies evaluating frequency of respiratory infections and graft outcomes are not available. OBJECTIVES/HYPOTHESIS: To determine whether there is a difference in allograft infection, allograft function and overall survival among CF lung transplant recipients with and without concomitant sinus surgery. STUDY DESIGN: Retrospective single-center study. METHODS: We examined 71 CF patients who underwent Ltx between 2009 and 2019 at our center. Fifty-nine patients had sinus surgery before or/and after transplantation and twelve did not undergo sinus surgery. We assessed the survival, the diagnosis of chronic allograft dysfunction (CLAD) and all elevated (> 5 mg/l) c-reactive protein episodes during the observed period. The infectious events of the upper and lower airways were categorized in mild infections (5-15 mg/l CRP) and severe infections (> 15 mg/l CRP). RESULTS: There was no difference in the long-time overall survival (p = 0.87) and no benefit in the short-term survival at 4 year post-transplant (p = 0.29) in both groups. There was no difference in both groups concerning CLAD diagnosis (p = 0.92). The incidence of severe upper and lower airway infections (CRP > 15 mg/l) was significantly decreased in the sinus surgery group (p = 0.015), whereas in mild infections there was a trend to decreased infections in the sinus surgery group (p = 0.056). CONCLUSIONS: CF patients undergoing Ltx benefit from extended endoscopic sinus surgery (eESS) in terms of frequency of severe infectious events of the upper and lower airways. There was no difference in overall survival and frequency of CLAD in the two groups.

Rhinologic outcome of endoscopic transnasal-transsphenoidal pituitary surgery: an institutional series, systematic review, and meta-analysis.

PURPOSE: We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery. METHODS: Retrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed. RESULTS: The institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher's exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0-2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1-3.0), a postoperative synechiae rate of 7.5% (IQR 1.8-19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5-5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting. CONCLUSION: Early and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care.

Progression of Rhinitis to Rhinosinusitis: A Cohort Study.

INTRODUCTION: Chronic rhinitis (CR) and rhinosinusitis are prevalent conditions affecting people all over the world. Their exact relationship is still not fully understood. We sought to find out, whether CR is a risk factor for chronic rhinosinusitis (CRS) and which main subgroup or other factors could be predisposing. METHODS: Patients with diagnosed CR between 2005 and 2010 were selected from the electronic medical record and were contacted by phone call. They were interviewed and screened for possible CRS using internationally approved questionnaires, e.g. NOSE-D and SNOT-20-GAV. Those with elevated scores were invited for a clinical examination. RESULTS: Of 113 patients available for statistical analysis (48/65 = f/m), mean age of 52 ± 15 years, 13 patients were diagnosed with CRS. Extrapolated for the total cohort of 334, calculated prevalence was 9.5%. No statistical significantly higher probability of developing CRS for either main subgroup of CR was found. Age of onset, prior surgery of the nose, and use of topical nasal treatments were associated with the development of CRS in multivariate analyses (OR = 0.1, 3.2, and 3.2, respectively). DISCUSSION/CONCLUSIONS: Only a small number of rhinitis patients developed CRS, questioning the paradigm of CR being a clear risk factor for CRS.

Direct platelet adhesion potentiates group 2 innate lymphoid cell functions.

BACKGROUND: Platelets are thought to be involved in the pathophysiology of asthma, presumably through direct adhesion to inflammatory cells, including group 2 innate lymphoid cells (ILC2s). Here, we tried to elucidate the effects of platelet adhesion to ILC2s in vitro and in vivo, as well as the mechanisms involved. METHODS: Alternaria-induced ILC2-dependent airway inflammation models using wild-type and c-mpl-/- mice were evaluated. Both purified CD41+ and CD41- ILC2s were cultured with IL-2 and IL-33 to determine in vitro Type 2 (T2) cytokine production and cell proliferation. RNA-seq data of flow-cytometry-sorted CD41+ and CD41- ILC2s were used to isolate ILC2-specific genes. Flow cytometry was performed to determine the expression of CD41 and adhesion-related molecules on ILC2s in both mouse and human tissues. RESULTS: T2 inflammation and T2 cytokine production from ILC2s were significantly reduced in the c-mpl-/- mice compared to wild-type mice. Platelet-adherent ILC2s underwent significant proliferation and showed enhanced T2 cytokine production when exposed to IL-2 and IL-33. The functions of ILC2-specific genes were related to cell development and function. Upstream regulator analysis identified 15 molecules, that are thought to be involved in ILC2 activation. CD41 expression levels were higher in ILC2s from human PBMCs and mouse lung than in those from secondary lymphoid tissues, but they did not correlate with the P-selectin glycoprotein ligand-1 or CD24 expression level. CONCLUSION: Platelets spontaneously adhere to ILC2s, probably in the peripheral blood and airways, thereby potentiating ILC2s to enhance their responses to IL-33.

Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines.

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.

Real-Life Experience of Monoclonal Antibody Treatments in Chronic Rhinosinusitis with Nasal Polyposis.

INTRODUCTION: Few studies assess biologicals such as, omalizumab, mepolizumab, benralizumab, and dupilumab in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The reported success rate in these studies differ, and it remains uncertain if there are any biomarkers to predict successful therapy. Our aim was to analyze the therapeutic outcome in a real life setting and to identify predictive biomarkers for successful treatment. METHODS: Data from patients with CRSwNP treated with a monoclonal antibody between November 2014 and January 2020 were analyzed retrospectively. Improvement in the polyp score and clinical symptoms like nasal obstruction, sense of smell, nasal discharge, and facial pain were evaluated. Other characteristics, including use of nasal or systemic steroids, comorbidities, previous history of sinus surgery, eosinophilia tissue, blood values (eosinophils, total immunoglobulin E, eosinophilic cationic protein, and interleukin 5), and allergic sensitization in serum were also investigated to identify possible predictive biomarkers. RESULTS: Forty-eight treatments in 29 patients (m/f = 15/14) aged 27-70 years were reviewed. Treatments with mepolizumab showed the best success rates (78.9%), followed by omalizumab (50%) and benralizumab treatments (50%). However, a correlation between biomarkers and treatment success could not be found. DISCUSSION/CONCLUSION: Treatment of CRSwNP with biologicals is a promising option for severe cases not responding to conventional therapy, including difficult-to-treat patients. Predictive biomarkers for a successful treatment could not be identified, but the reduction of eosinophilic cationic protein was linked with the response.

Outside-in hypothesis revisited: The role of microbial, epithelial, and immune interactions.

OBJECTIVE: Our understanding of the origin of allergic diseases has increased in recent years, highlighting the importance of microbial dysbiosis and epithelial barrier dysfunction in affected tissues. Exploring the microbial-epithelial-immune crosstalk underlying the mechanisms of allergic diseases will allow the development of novel prevention and treatment strategies for allergic diseases. DATA SOURCES: This review summarizes the recent advances in microbial, epithelial, and immune interactions in atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, and asthma. STUDY SELECTIONS: We performed a literature search, identifying relevant recent primary articles and review articles. RESULTS: Dynamic crosstalk between the environmental factors and microbial, epithelial, and immune cells in the development of atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, and asthma underlies the pathogenesis of these diseases. There is substantial evidence in the literature suggesting that environmental factors directly affect barrier function of the epithelium. In addition, T-helper 2 (TH2) cells, type 2 innate lymphoid cells, and their cytokine interleukin 13 (IL-13) damage skin and lung barriers. The effects of environmental factors may at least in part be mediated by epigenetic mechanisms. Histone deacetylase activation by type 2 immune response has a major effect on leaky barriers and blocking of histone deacetylase activity corrects the defective barrier in human air-liquid interface cultures and mouse models of allergic asthma with rhinitis. We also present and discuss a novel device to detect and monitor skin barrier dysfunction, which provides an opportunity to rapidly and robustly assess disease severity. CONCLUSION: A complex interplay between environmental factors, epithelium, and the immune system is involved in the development of systemic allergic diseases.

Assessing the surgical outcome of the "chopsticks" technique in endoscopic transsphenoidal adenoma surgery.

OBJECTIVE: The "chopsticks" technique is a 3-instrument, 2-hand mononostril technique that has been recently introduced in endoscopic neurosurgery. It allows a dynamic surgical view controlled by one surgeon only while keeping bimanual dissection. Being a mononostril approach, it requires manipulation of the mucosa of one nasal cavity only. The rationale of the technique is to reduce nasal morbidity without compromising surgical results and complication rates. There are, however, no data available on its results in endoscopic surgery (transsphenoidal surgery [TSS]) for pituitary adenoma. METHODS: The authors performed a cohort analysis of prospectively collected data on 144 patients (156 operations) undergoing TSS using the chopsticks technique with 3T intraoperative MRI. All patients had at least 3 months of postoperative neurosurgical, endocrinological, and rhinological follow-up (Sino-Nasal Outcome Test-20 [SNOT-20] and Sniffin' Sticks). The surgical technique is described, and the achieved gross-total resection (GTR) and extent of resection (EOR) together with patients' clinical outcomes and complications are descriptively reported. RESULTS: On 3-month postoperative MRI, GTR was achieved in 71.2% of patients with a mean EOR of 96.7%. GTR was the surgical goal in 122 of 156 cases and was achieved in 106 of 122 (86.9%), with a mean EOR of 98.7% (median 100%, range 49%-100%). There was no surgical mortality. At a median follow-up of 15 months (range 3-70 months), there was 1 permanent neurological deficit. As of the last available follow-up, 11.5% of patients had a new pituitary single-axis deficit, whereas 26.3% had improvement in endocrinological function. Three patients had new postoperative hyposmia. One patient had severe impairment of sinonasal function (SNOT-20 score > 40). The operation resulted in endocrine remission in 81.1% of patients with secreting adenomas. CONCLUSIONS: This study shows that the chopsticks technique confers resection and morbidity results that compare favorably with literature reports of TSS. This technique permits a single surgeon to perform effective endoscopic bimanual dissection through a single nostril, reducing manipulation of healthy tissue and thereby possibly minimizing surgical morbidity.

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized. OBJECTIVE: We sought to determine the factors that induce regulatory innate lymphoid cells (ILCregs). METHODS: IL-10+ ILCregs induced from ILC2s by using retinoic acid (RA) were analyzed with RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissue from healthy subjects and patients with chronic rhinosinusitis with nasal polyps and lung tissue from house dust mite- or saline-treated mice. RESULTS: RA induced IL-10 secretion by human ILC2s but not type 2 cytokines. IL-10+ ILCregs, which were converted from ILC2s by means of RA stimulation, expressed a regulatory T cell-like signature with expression of IL-10, cytotoxic T lymphocyte-associated protein 4, and CD25, with downregulated effector type 2-related markers, such as chemoattractant receptor-homologous molecule on TH2 cells and ST2, and suppressed activation of CD4+ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy subjects or lung tissue from saline-treated mice, but numbers were increased in nasal tissue from patients with chronic rhinosinusitis with nasal polyps and in lung tissue from house dust mite-treated mice. Enzymes for RA synthesis were upregulated in airway epithelial cells during type 2 inflammation in vivo and by IL-13 in vitro. CONCLUSION: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs.

The Zurich Pituitary Score predicts utility of intraoperative high-field magnetic resonance imaging in transsphenoidal pituitary adenoma surgery.

BACKGROUND: It is currently unclear if there are subsets of patients undergoing transsphenoidal surgery (TSS) in which intraoperative high-field magnetic resonance imaging (3T-iMRI) is particularly advantageous. We aimed to investigate whether a radiological grading scale predicts the utility of 3T-iMRI in pituitary adenoma (PA) TSS. METHODS: From a prospective registry, patients who underwent endoscopic TSS for PA using 3T-iMRI were identified. Adenomas were graded using the Zurich Pituitary Score (ZPS). We assessed improvement after 3T-iMRI in terms of gross total resection (GTR), residual volume (RV), and extent of resection (EOR). RESULTS: Among 95 patients, rates of conversion to GTR after 3T-iMRI decreased steadily from 33% for grade I to 0% for grade IV adenomas, with a statistically significant conversion rate only for grade I (p = 0.008) and grade II (p < 0.001). All grade I adenomas were completely resected after 3T-iMRI. Median RV change was statistically significant for grades I to III, but not for grade IV (p = 0.625). EOR improvement ranged from a median change of 0.0% (IQR 0.0-4.5%) for grade I to 4.4% (IQR 0.0-9.0%) for grade IV, with a significant improvement only for grades I to III (p < 0.05). CONCLUSIONS: Interestingly, this study shows that clinical utility of 3T-iMRI is highest in the more "simple" adenomas (ZPS grades I-II) than for the more "complex" ones (ZPS grade III-IV). Grade I adenomas are amenable to GTR if 3T-iMRI is implemented. In grade III adenomas, EOR and RV can be improved to clinically relevant levels. Conversely, in grade IV adenomas, 3T-iMRI may be of limited use.

Current concepts in advanced sinonasal mucosal melanoma: a single institution experience.

PURPOSE: To present outcome measures of sinonasal mucosal melanoma (SMM) patients with particular focus on current radiological and therapeutic options, especially in the non-curative setting (immunotherapy). METHODS: Retrospective study on SMM patients treated at our institution between January 1992 and December 2018. RESULTS: FDG-PET/MRI has emerged as the new hybrid imaging modality, addressing the need for high local tissue contrast in the paranasal sinuses and the skull base, while allowing for whole-body staging in search for distant metastases, including the brain. Primary treatment protocols consisted of tumor resection in 30/34 patients (88%), palliative radiation therapy (RT) in 3/34 patients (9%) and best supportive care therapy in 1/34 patient (3%). Of all the initially operated patients, 25/30 patients (83%) received adjuvant RT. A total of 9/34 patients (26%) was treated with immunotherapy after the previous combined therapy. For patients treated in curative intention, we observed a 1-year overall survival (OS) of 60% (18/30 patients) and a 3-year OS of 40% (12/30 patients). For patients treated with immunotherapy, median progression-free survival (PFS) was 5 months (IQR 0-13.75), with a maximum PFS of 16 months (combination of nivolumab and ipilimumab). However, there was no difference in OS in patients treated with immunotherapy vs. no immunotherapy (log rank 0.99). CONCLUSIONS: Sinonasal mucosal melanoma is a highly aggressive tumor, requiring multimodal therapy and developing a substantial incidence of distant metastases. The introduction of FDG-PET/MRI offers new possibilities in the radiological assessment of the tumor and immunotherapy has altered the management in the non-curative setting, resulting in a substantial progression-free survival in selected cases.

[The efficacy of omalizumab in the treatment of chronic rhinosinusitis with nasal polyps: a discussion of 2 refractory cases]. / Efficacité de l'omalizumab dans la polypose nasale: à propos de deux cas.

Nasal polyposis is a specific phenotype of chronic rhinosinusitis (CRS). Some cases can be managed with topical and infrequent use of systemic steroids, while many patients require surgery. Despite postoperative, regular steroid administration, recurrences may be found especially in patients suffering from Aspirin exacerbated respiratory disease (AERD), a particularly severe form of CRS with polyps, asthma and non-steroid-anti-inflammatory-drug (NSAID) intolerance. We report two cases of difficult-to-treat AERD patients following revision surgery, treated with monoclonal anti-IgE antibody (omalizumab) and successful control of the disease and symptoms. Omalizumab may be a promising alternative in selected cases of CRS with nasal polyps to avoid overuse of systemic steroids and frustrating repetition of paranasal sinus surgeries.

La rhinosinusite chronique (RSC) touche 15 % de la population et se caractérise par l'obstruction et l'écoulement nasaux pendant plus de trois mois. Les formes sévères de la RSC sont associées à la présence de polypes nasaux. Le traitement de première ligne sont des corticoïdes topiques, qui ne sont pas toujours efficaces et certains patients ont besoin de plusieurs cures de stéroïdes per os et chirurgies nasales répétitives pour stabiliser la maladie. Ce cercle vicieux s'observe souvent dans le syndrome de Widal (polypes, asthme et intolérance aux AINS). On rapporte deux cas de Widal avec interruption de cette boucle, obtenue par l'application de l'anticorps monoclonal anti-IgE omalizumab. L'omalizumab pourrait être une alternative dans certains cas de RSC pour limiter la surutilisation de stéroïdes et la répétition frustrante de chirurgie nasale.

Predicting extent of resection in transsphenoidal surgery for pituitary adenoma.

BACKGROUND: The extent of resection (EOR) is a crucial outcome parameter in transsphenoidal pituitary surgery (TSS), and is linked to endocrinological outcome, postoperative morbidity, and mortality. We aimed to build a robust, quantitative, and easily reproducible imaging score able to predict EOR in TSS. METHODS: The ratio (R) between the maximum horizontal adenoma diameter and intercarotid distance at the horizontal C4 segment was used to stratify our patient series in four classes: class I R ≤ 0.75, class II 0.75 < R ≤ 1.25, and class III R ≥ 1.25. Class IV included adenomas which completely encased the internal carotid artery. The resulting score was internally validated for robustness. RESULTS: One hundred sixteen patients were included in the study, of which 96 (83%) for derivation and 20 (17%) for validation. EOR showed significant differences between grades (grade I, 100%; II, 97.9%; III, 94.2%; IV, 87.2%; all P < 0.05). The same applied to residual volume (RV) (grade I, 0 cm3; II, 0.08 cm3; III, 1.11 cm3; IV, 1.63 cm3; all P < 0.05). Differences in gross total resection (GTR) were statistically significant among classes I, II, and III (P < 0.05). The incidence of residual adenoma in the cavernous sinus increased also constantly from grade I up to grade IV although a significant difference was only found between grades III and II (P = 0.004). The score performed equally well in the validation cohort. Inter-observer agreement was high, with intraclass correlation coefficients > 0.89 for measurement of both the horizontal tumor diameter and the ICD among two independent raters (P < 0.001). CONCLUSIONS: The proposed score is a simple and reproducible tool which reliably predicts surgical outcome including EOR, RV, and GTR of pituitary adenoma patients undergoing TSS.

Delayed diagnosis of sinonasal lymphoma due to bilateral manifestation.

The objective of this study is to analyze the presenting symptoms, the time to correct diagnosis and outcome of a European patient cohort with sinonasal lymphoma focusing on unilateral vs. bilateral sinonasal involvement. In a retrospective setting in a European tertiary referral center, eleven patients (9 males, 2 females) with sinonasal lymphoma diagnosed between 2002 and 2015 were identified and divided into a unilateral and bilateral group according to their CT finding. Clinical findings on first presentation, the presence of B symptoms, the radiologic findings, overall survival and disease-specific survival were assessed. 55 % of the patients suffered from bilateral manifestation, which was associated with a delayed diagnosis (10 vs. 1.5 months, p < 0.05). B symptoms (67 vs. 0 %) and death of disease (50 vs. 0 %) were observed only in the bilateral group. Nasal NK/T-cell lymphoma was the most frequent diagnosis, followed by diffuse large B-cell lymphoma. Bilateral mucosal manifestation with B symptoms was shown to be common within the rare entity of sinonasal lymphomas and patients with bilateral sinonasal manifestation are at risk for a delayed diagnosis with worse outcome.