Multidisciplinary Decision-Making-ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study).

PURPOSE OF REVIEW: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments. RECENT FINDINGS: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved.

Dupilumab: a delayed response in asthmatic and atopic patients treated for chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a common disease, which was previously approached with sinus surgery or systemic corticosteroids. The advent of biological therapies radically changed the approach to this disease. On the other hand, there is scarce scientific evidence of how specific subsets of patients respond to this treatment. METHODS: this is a monocentric, prospective study investigating the long-term efficacy on biweekly 300 mg dupilumab therapy in CRSwNP, prescribed to 61 patients. Patients were evaluated at baseline and every 2 months for the first 6 months, then at 9, 12, 16, 20 and 24 months. RESULTS: dupilumab proved to be an effective treatment, neatly improving both subjective and objective measurements in CRSwNP. The main finding of the study is the difference between specific subgroups of patients: while the overall response is similar, patients with Th2 comorbidities such as asthma and atopy tend to reach a stable response later, with the improvement ongoing even after 6 months of therapy, while non-asthmatic, non-atopic patients attain an earlier stability in response. CONCLUSIONS: dupilumab provides an excellent long-term control of CRSwNP, but the response in asthmatic and atopic patients appears to be different and delayed when compared to non asthmatic and non atopic ones.

Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD-1 levels. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were identified in four patients belonging to this group. Their blood lymphocytes showed shortened telomeres, while their cTfh were more prone to apoptosis. These data point toward a novel pathogenetic mechanism in CVID, whereby alterations in DNA repair and telomere elongation might predispose to antibody deficiency. A Th1, highly activated but exhausted and apoptotic cTfh phenotype was associated with this form of CVID.

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.

Comparison of guidelines for prescription and follow-up of biologics for chronic rhinosinusitis with nasal polyps.

PURPOSE: To compare international and regional guidelines for prescription and monitoring of response to biologics in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: A literature review was performed to identify publications reporting indications for biologic therapy in CRSwNP. A full-text reading identified specific issues for comparison: prior surgery, evidence of type 2 inflammation (T2I), smell function, comorbidities, use of systemic corticosteroids, impact on quality of life, and endoscopic and CT findings were compared for the prescription, while the monitoring of the treatment was described in relation to timing, classification of response and criteria for withdrawal. RESULTS: Ten publications were found. Prior surgery was strictly necessary in five guidelines, while in all the remaining it was variably recommended. A confirmation of T2I was considered necessary in one publication, unnecessary in two, and recommended or constituted only one of the factors to consider in seven. All the other issues analyzed were variably considered. Reevaluation was suggested at 4-6 months and 1 year, mostly assessing improvement in the same criteria used for prescription. CONCLUSIONS: A combination of subjective and objective findings is used for the identification of patients with CRSwNP who are indicated for biologic therapy. Major debate has developed on the need for previous surgery, which is generally recommended, or strictly necessary for some authors. Confirmation of T2I is generally suggested, but compulsory only in a minority of guidelines. Smell function, use of systemic corticosteroids, and the impact on quality of life are the other factors most frequently considered.

The use of near-infrared autofluorescence during total laryngectomy with hemi- or total thyroidectomy.

PURPOSE: The aim of this study is to describe the use of near-infrared autofluorescence (NIR-AF) to identify and preserve parathyroid glands (PGs) in a group of patients with advanced hypopharyngeal/laryngeal cancer undergone total (pharyngo)laryngectomy with hemi- or total thyroidectomy. METHODS: At San Raffaele Hospital, Milan (Italy), from January 2021 to May 2021, 7 patients affected by cT4a laryngeal squamous cell carcinoma (SCC) underwent surgery using an autofluorescence detection system (Fluobeam-Fluoptics®). For proper surgical planning, the demolition phase envisaged extension of the intervention to 4 hemithyroidectomies and 3 total thyroidectomies associated, respectively, with homolateral or bilateral CCND. Serum calcium, ionized calcium, and parathyroid hormone (PTH) levels at post-operative day (POD) 1 and 2 and at 2 weeks after surgery were monitored. Finally, we compared the data obtained with a cohort of patients who underwent surgery without the adoption of NIR-AF. RESULTS: With the use of NIR-AF, 18/20 PGs were identified, of which 7/18 were preserved exclusively thanks to the use of autoflorescence. The technique also made it possible to identify and isolate three PGs from the surgical specimen, which were subsequently transplanted only after intraoperative histological confirmation. On POD-1, 3/7 patients (42.8%) were hypocalcemic; on POD-2 and after 2 weeks only 1/7 patient (14.2%) was hypocalcemic. Comparing the two groups, we highlighted that the utilization of NIR-AF was related to a significant decrease of median serum (p = 0.026) and ionized calcium levels (p = 0.017) 2 weeks after surgery. Using this new technology, in no case did definitive histological examination reveal the presence of PGs in the surgical specimen, reaching an accuracy of 100%. CONCLUSIONS: In our cohort of patients who underwent total (pharyngo)laryngectomy with hemi- or total thyroidectomy, the use of near-infrared autofluorescence improved medium term postoperative hypocalcemia rates. This new technology helps to achieve a better calcemic outcome compared to the standard naked eye approach, since it helps the surgeon to identify and preserve parathyroid glandular tissue with a lower incidence of post-operative hypocalcemia.

Activation of Mast Cells by Neuropeptides: The Role of Pro-Inflammatory and Anti-Inflammatory Cytokines.

Mast cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in the scientific literature; it is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptide substance P (SP), corticotropin-releasing hormone (CRH), and neurotensin, and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

Transcranial extradural subtemporal repair for sphenoid sinus lateral recess meningoencephalocele: technical note.

Cranial meningoencephalocele is a rare condition consisting of the herniation of meninges, CSF, and brain tissue through a cranial or skull base defect. Sphenoid sinus lateral recess meningoencephalocele is of particular interest due to the complex anatomy surrounding the bone defect and their demanding surgical management. In this technical note, we reported a step-by-step description of a rare case of sphenoid sinus lateral recess meningoencephalocele causing headache due to recurrent cerebrospinal fluid leak treated with a subtemporal craniotomy with extradural middle cranial fossa drilling and meningoencephalocele removal with multilayer reconstruction. The transcranial route is a safe and effective treatment for sphenoid sinus lateral recess meningoencephalocele repair. The subtemporal extradural approach allows for an optimal exposure of the relevant anatomy minimizing risks and improving the possibility to perform an effective multilayer skull base reconstruction.

Long-term results of a balloon-assisted endoscopic approach in failed dacryocystorhinostomies.

PURPOSE: Endoscopic endonasal balloon-assisted dacryoplasty is a minimally invasive surgical approach that can be applied after failure of dacryocystorhinostomy with recurrence of distal acquired lacrimal obstruction. METHODS: At the Department of Otolaryngology, San Raffaele Hospital, Milan (Italy), from December 2016 to October 2020, 14 patients underwent trans-nasal balloon-assisted dacryoplasty after a failed dacryocystorhinostomy (both external and endoscopic endonasal). The routinary pre-operative work-up included multidisciplinary study of the lacrimal disease, which consisted in primary ophthalmological and otorhinolaryngological visits associated with nasal endoscopy, in which a radiological exam was added if needed. The surgical approach includes pneumatic enlargement of the stenotic rhinostomy, created during the primary dacryocystorhinostomy, using a high-pressure trans-nasal balloon catheter. Anatomical success was considered when the ostium was patent upon irrigation, while functional success was considered as resolution of epiphora or free lacrimal flow on functional test. RESULTS: Among 14 patients included and after a mean follow-up of 19.5 months (range 13-51 months), anatomic success was achieved in 100% of patients and functional success was achieved in the 85.7% (12/14). Operative time ranged from 9 to 28 min (mean 18 min) and no complications were reported. CONCLUSION: Trans-nasal balloon-assisted dacryoplasty is a mini-invasive surgical approach to treat failed dacryocystorhinostomies with reliable and stable outcomes in the long term. The absence of post-surgical complications, high success rate and short operative time are the main features of this innovative procedure.

Hypereosinophilia management in patients with type 2 chronic rhinosinusitis treated with dupilumab: preliminary results.

PURPOSE: Biological therapies are gaining relevance in the management of CRSwNP with few adverse events reported. Among these, dupilumab, an anti-IL4-Ra monoclonal antibody, is frequently associated with hypereosinophilia (HE) which usually remains silent and progressively resolves, although some cases of systemic involvement occurs. The aim of this paper is to describe our experience and propose a management flowchart for HE during therapy with dupilumab. METHODS: Patients with CRSwNP who satisfied EPOS2020 criteria for biological therapies were included in this prospective study. Each case was discussed in a multidisciplinary meeting with subsequent prescription of dupilumab; all patients were candidates to follow-up bi-monthly for 6 months, while additional blood tests were scheduled in the event of HE. RESULTS: A total of 21 patients with a mean age of 48.4 years were enrolled. Of these, 15 of 21 presented an asthma comorbidity and 9 of 21 ASA sensitivity. Four patients (19%) developed HE with AEC > 1.5 × 109/L, whereas it occurred in 9.5% (two patients) if considered AEC > 3 × 109/L. No cases of hypereosinophilic syndrome were recorded. Following our decision-making flowchart, two patients received short-term corticosteroid therapy, whereas the other two were only eligible for closer follow-up. CONCLUSIONS: During dupilumab therapy, HE may occur and should be considered benign when < 3 × 109/L in the absence of organ involvement. Conversely, in case of HE ≥ 3 × 109/L, an empirical approach with short-term corticosteroid therapy should be considered to debulk the blood from eosinophils and prevent potential organ involvement.

Mast Cell Cytokines in Acute and Chronic Gingival Tissue Inflammation: Role of IL-33 and IL-37.

Much evidence suggests autoimmunity in the etiopathogenesis of periodontal disease. In fact, in periodontitis, there is antibody production against collagen, DNA, and IgG, as well as increased IgA expression, T cell dysfunction, high expression of class II MHC molecules on the surface of gingival epithelial cells in inflamed tissues, activation of NK cells, and the generation of antibodies against the azurophil granules of polymorphonuclear leukocytes. In general, direct activation of autoreactive immune cells and production of TNF can activate neutrophils to release pro-inflammatory enzymes with tissue damage in the gingiva. Gingival inflammation and, in the most serious cases, periodontitis, are mainly due to the dysbiosis of the commensal oral microbiota that triggers the immune system. This inflammatory pathological state can affect the periodontal ligament, bone, and the entire gingival tissue. Oral tolerance can be abrogated by some cytokines produced by epithelial cells and activated immune cells, including mast cells (MCs). Periodontal cells and inflammatory-immune cells, including mast cells (MCs), produce cytokines and chemokines, mediating local inflammation of the gingival, along with destruction of the periodontal ligament and alveolar bone. Immune-cell activation and recruitment can be induced by inflammatory cytokines, such as IL-1, TNF, IL-33, and bacterial products, including lipopolysaccharide (LPS). IL-1 and IL-33 are pleiotropic cytokines from members of the IL-1 family, which mediate inflammation of MCs and contribute to many key features of periodontitis and other inflammatory disorders. IL-33 activates several immune cells, including lymphocytes, Th2 cells, and MCs in both innate and acquired immunological diseases. The classic therapies for periodontitis include non-surgical periodontal treatment, surgery, antibiotics, anti-inflammatory drugs, and surgery, which have been only partially effective. Recently, a natural cytokine, IL-37, a member of the IL-1 family and a suppressor of IL-1b, has received considerable attention for the treatment of inflammatory diseases. In this article, we report that IL-37 may be an important and effective therapeutic cytokine that may inhibit periodontal inflammation. The purpose of this paper is to study the relationship between MCs, IL-1, IL-33, and IL-37 inhibition in acute and chronic inflamed gingival tissue.

Total thyroidectomy with intraoperative neural monitoring and near-infrared fluorescence imaging.

PURPOSE: To describe our personal experience during aclassic complete thyroidectomy adopting both intraoperative neural monitoringand near-infrared autofluorescence. METHODS: In October 2021, 20 patients underwent totalthyroidectomy for benign and malignant conditions: 13 patients were affected bymultinodular goiter, 2 by Graves' disease, and 5 by indeterminate lesions (3Tir-3B and 2 Tir-3A). For each patient, intraoperative neural monitoring of therecurrent laryngeal nerve and near-infrared autofluorescence were used. RESULTS: Overall, 76/80 (95.0%) parathyroid glands weredetected: 34/76 (44.7%) were identified by the surgeon during the dissection,while 42/76 (55.3%) were detected by the near-infrared camera before thesurgeon saw them with naked eye. Indocyanine green angiography was adopted inall the patients, and in 2 cases, parathyroid gland autotransplantation wasperformed since 2 parathyroid glands resulted devascularized after dissection.Operative time ranged from 113 to 201 min (mean 156 min). CONCLUSION: Together with intraoperative neural monitoring,near-infrared autofluorescence is a reliable device in thyroid surgery. Furtherprospective studies are necessary to establish if the adoption ofautofluorescence may result in long-term benefit in terms of calcemia.

Gene Expression Analysis in Patients with Cocaine-Induced Midline Destructive Lesions.

BACKGROUND AND OBJECTIVES: Cocaine users may present with positive antineutrophil cytoplasmic antibodies (ANCA) and severe midline destructive lesions (CIMDL) which are histologically characterized by massive apoptosis. However, histopathological and laboratory studies suggest that autoimmunity may not be the main pathogenic driver. We analyzed gene expression both in cell lines of nasal mucosa exposed to cocaine and in CIMDL patients to determine whether genetic predisposition might cause such lesions, which are observed in a minority of cocaine abusers. MATERIALS AND METHODS: The genetic expression profile of nasal mucosa exposed to cocaine was analyzed. Rare variants of expressed genes were searched in patients with CIMDL using exome sequencing and bio-informatics. RESULTS: We identified 462 genes that were induced by cocaine, mainly related to apoptosis and autophagy in response to oxidative stress. Under the hypothesis that genes linked to the phenotype are also induced by cocaine itself, a rare variants burden test was performed to select genes that were significantly enriched in rare mutations. Next, 11 cocaine abusers with CIMDL and no other relevant medical comorbidities underwent exome sequencing, and 12 genes that were significantly enriched in the burden test and present in at least 10 patients were identified. An in-depth analysis of these genes revealed their involvement in apoptosis, tissue homeostasis, autophagy, and response to oxidative stress. CONCLUSIONS: Oxidative stress and rare genetic alterations in the response to reactive oxygen species, apoptosis, autophagy, and tissue regeneration are plausible drivers of damage affecting nasal mucosa exposed to cocaine crystals and, consequently, the pathogenic mechanism behind CIMDL.

Best treatments available for distal acquired lacrimal obstruction: A systematic review and meta-analysis.

BACKGROUND: Epiphora is a common clinical sign whose primary cause is post-canalicular lacrimal obstruction. Treatment is both surgical and non-surgical. In the literature, there is some evidence to suggest that some treatments are superior to others, but there are no direct comparative data in this regard. OBJECTIVE OF REVIEW: To analyse the success rates of all available treatments to resolve post-canalicular acquired lacrimal obstruction. TYPE OF REVIEW: Systematic review and meta-analysis. SEARCH STRATEGY: A literature search was conducted in the US National Library of Medicine (PubMed), EMBASE, SCOPUS and Cochrane databases with a final search performed in January 2020. EVALUATION METHOD: The search strategy identified articles published later than 2000 with at least 50 procedures performed both surgically (external dacryocystorhinostomy [EXT-DCR], endoscopic dacryocystorhinostomy [END-DCR] and transcanalicular laser dacryocystorhinostomy [TCL-DCR]) and non-surgically (balloon dacryoplasty [DCP], probing-stenting [SP] and polyurethane stent [PoS]). The primary outcome was functional success, defined as symptom resolution or less than MUNK 2 scale; in addition to this, the influence of adjunctive treatments, such as application of mitomycin C and post-procedural silicone stenting, was evaluated. RESULTS: In total, 14 958 papers were selected, 440 of which were reviewed after screening; 55 were included after full-text review, which involved 9337 procedures. Mean success rate was 48.9% (35.7%-62.3%) for DCP, 54.4% (41.8%-66.5%) for SP, 73.6% (59.7%-84%) for PoS, 80% (75.1%-84%) for TCL-DCR, 89.8% (83.3%-93.9%) for EXT-DCR and 89.5% (87.2%-91.5%) for END-DCR. Among all procedures, a difference was noted between DCP and END-DCR (P < .001), DCP and EXT-DCR (P < .001), SP and END-DCR (P < .001), SP and EXT-DCR (P < .001), END-DCR and PoS (P = .016), and END-DCR and TCL-DCR (P = .001); no differences were noted between END-DCR and EXT-DCR (P = 1.00), EXT-DCR and PoS (P = .121) and EXT-DCR and TCL-DCR (P = .223). Considering surgical procedures, no differences were seen if a silicone stenting was applied, whereas, due to heterogeneity of the literature data, no statistical analysis was feasible for application of mitomycin C. CONCLUSIONS: Our analyses suggest that, among all procedures available, END-DCR and EXT-DCR should be considered as treatments of choice to resolve distal acquired lacrimal obstruction.

The disease of Sigmund Freud: oral cancer or cocaine-induced lesion?

PURPOSE: Sigmund Freud, the father of modern psychoanalysis, suffered from what was considered to be a malignant tumour spreading from the back of his palate. He underwent numerous surgical interventions and radiation therapy over the course of 16 years. Such a long survival casts a shadow of doubt on the diagnosis of oral cancer that was given to Freud. METHODS: The book "Freud: Living and Dying", in which the personal physician of Freud described in detail his patient's fight with oral cancer, was reviewed. Current and past evidence, as well as epidemiological data, on oral cancer and cocaine-induced midline destructive lesions were also reviewed. RESULTS: Tobacco and cocaine are both responsible for oral lesions and Freud was a dedicated cigar smoker as well as a user and defender of cocaine. Freud's medical records indicate that the main cause of Freud's oral disease was excessive smoking. On the other hand, the diagnosis of oral cancer does not seem to be entirely consistent with the 16-year-long survival of Freud. Freud used cocaine regularly in the 1890s, as reported by his personal physician, and it is possible that he continued taking it beyond that time period without feeling the need to inform his doctor. CONCLUSIONS: It is possible that the lesion that progressively and very slowly eroded the splanchnocranial structures of Freud was not a bona-fide cancerous malignancy, but rather, the necrotizing effect of cocaine use that has been previously reported to be responsible for some massive facial destructive lesions.

Decrease of Horizontal Canal Vestibulo-Oculomotor Reflex Gain in the Elderly with Dysequilibrium without Lifetime Vertigo.

BACKGROUND/AIMS: Unsteadiness in the elderly is a frequent complaint and a strong predictor of falls and psychological distress. Although there is a general consensus that it is a multifactorial condition, recent studies have focused on the role of aging of the vestibular system as a possible cofactor. The aim of our work was to assess horizontal canal function in the elderly. METHODS: We evaluated the gain of horizontal vestibulo-ocular reflex (VOR) with a video head impulse test on a sample of 58 subjects aged >70 years without lifetime episodes of vertigo and correlated the value with different clinical conditions (hypertension, diabetes, prior cardiovascular and vascular disorders of the central nervous system, and falls). RESULTS: The mean value of the gain was 0.86 ± 0.12, and people aged between 70 and 80 years presented higher values (0.90 ± 0.1) compared to those >80 years (0.81 ± 0.13; p = 0.025). Previous vascular disorders of the central nervous system were a predictor of decreased VOR gain (p = 0.0003). A nonparametric analysis demonstrated that sex, age, and VOR gain (p ˂ 0.0001) were predictive of falls. CONCLUSIONS: Our data support the hypothesis of a decrease of VOR gain in the elderly. The decrease of canal function may therefore play a role in the risk of falls in the elderly.

Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers.

OBJECTIVE: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity. METHODS: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio. RESULTS: Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio >20% on histological examination, however, were observed only in patients with IgG4-RD. CONCLUSIONS: Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.

Columella reconstruction with an inferiorly-based philtral advancement flap in a cocaine abuser.

Nasal columella defects can significantly impair aesthetic appearance. Columella reconstruction can be very challenging for surgeons, especially if due to cocaine abuse. The case of a 32-year-old male patient with subtotal columellar necrosis secondary to cocaine abuse is presented. An inferiorly based philtral advancement flap was performed to cover the defect. Aesthetic outcome was the primary goal of surgery. Reconstruction led to good aesthetic and functional results.

Are atopy and eosinophilic bronchial inflammation associated with relapsing forms of chronic rhinosinusitis with nasal polyps?

BACKGROUND: The aetiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is still unknown. The role of atopy and the concept of united airways in such patients are still a matter of debate. In this pilot study we aimed at evaluating the degree of eosinophilic inflammation and the frequency of atopy in a cohort of CRSwNP patients candidate for Functional Endoscopic Sinus Surgery (FESS) and assessing the association between these factors and relapsing forms of CRSwNP. METHODS: 30 patients (18 men, 12 women) with CRSwNP eligible for FESS were evaluated before and after surgery. Preoperative investigation included: history of previous relapse after FESS, clinical and laboratory allergologic assessment, spirometry, methacholine challenge, blood eosinophilia and determination of the fraction of nitric oxide in exhaled air (FeNO). Nasal fibroendoscopy, spirometry and FeNO determination were also assessed prospectively at 3 and 27 months post-FESS. RESULTS: 18/30 subjects were atopic, 6/18 (33 %) were monosensitized, 16/30 (53 %) were asthmatics and 10/30 (33 %) had non steroidalantinflammatory drugs (NSAIDs) hypersensitivity. Twenty-one patients (70 %) were classified as relapsers, 15/18 (83 %) among atopics, 6/12 (50 %) among non atopics (p = 0.05). Among patients with NSAIDs hypersensitivity, 9/10 (90 %) were relapsers. The median IgE concentration was 161.5 UI/mL in relapsers and 79 UI/mL in non-relapsers (ns). The mean FeNO decreased after FESS (43.1-26.6 ppb) in 84 % of patients, but this effect disappeared over time (FeNO = 37.7 ppb at 27 months). Higher levels of FeNO pre-FESS were detected in atopics, and in particular in relapsing ones (median 51.1 ppb vs 22.1, ns). Higher levels of FeNO pre-FESS were detected in asthmatic patients, especially in those who relapsed (median: 67 vs 64.85 ppb in non-relapsed patients, ns). The Tiffeneau Index (FEV1/FVC) was significantly lower in asthmatic relapsers than in non relapsers asthmatics (94.7 ± 11.1 versus 105 ± 5.9-p = 0.04). Patients with asthma and atopy had a major risk of relapse (p = 0.05). CONCLUSION: In our pilot study, atopy, severe asthma, bronchial inflammation, NSAIDs hypersensitivity and high level of total IgE are possible useful prognostic factors for the proneness to relapse after FESS. The role of allergy in CRSwNP pathogenesis should consequently be given deeper consideration. Allergen specific immunotherapy, combined with anti-IgE therapy, may have an immunomodulatory effect preventing polyps relapse and need to be investigated.