Standardizing digital biobanks: integrating imaging, genomic, and clinical data for precision medicine.

Advancements in data acquisition and computational methods are generating a large amount of heterogeneous biomedical data from diagnostic domains such as clinical imaging, pathology, and next-generation sequencing (NGS), which help characterize individual differences in patients. However, this information needs to be available and suitable to promote and support scientific research and technological development, supporting the effective adoption of the precision medicine approach in clinical practice. Digital biobanks can catalyze this process, facilitating the sharing of curated and standardized imaging data, clinical, pathological and molecular data, crucial to enable the development of a comprehensive and personalized data-driven diagnostic approach in disease management and fostering the development of computational predictive models. This work aims to frame this perspective, first by evaluating the state of standardization of individual diagnostic domains and then by identifying challenges and proposing a possible solution towards an integrative approach that can guarantee the suitability of information that can be shared through a digital biobank. Our analysis of the state of the art shows the presence and use of reference standards in biobanks and, generally, digital repositories for each specific domain. Despite this, standardization to guarantee the integration and reproducibility of the numerical descriptors generated by each domain, e.g. radiomic, pathomic and -omic features, is still an open challenge. Based on specific use cases and scenarios, an integration model, based on the JSON format, is proposed that can help address this problem. Ultimately, this work shows how, with specific standardization and promotion efforts, the digital biobank model can become an enabling technology for the comprehensive study of diseases and the effective development of data-driven technologies at the service of precision medicine.

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.

The Starkstein Apathy Scale-Italian Version: An Update.

Apathy can manifest in various neuropsychiatric conditions, as well as in individuals who experience significant stressful life events or suffer from underlying internal medical conditions. The Starkstein Apathy Scale (SAS) is recognized as a reliable screening tool, besides being endorsed by the International Parkinson and Movement Disorder Society to assess apathy in patients with Parkinson's disease. Recently, the Italian version of this scale (SAS-I) has been introduced. Furthermore, normative data have been provided on a large sample of Italian healthy individuals. Here we present the official Italian translation of the SAS, along with clarifications regarding its administration. Also, we supply details concerning the scale's factorial structure, inter-item conditional associations and item performance by using EFA, Network analysis, and IRT modelling for polytomous items.

Open-door extended endoscopic transorbital technique to the paramedian anterior and middle cranial fossae: technical notes, anatomomorphometric quantitative analysis, and illustrative case.

OBJECTIVE: The superior eyelid endoscopic transorbital approach (SETOA) provides a direct and short minimally invasive route to the anterior and middle skull base. Nevertheless, it uses a narrow corridor that limits its angles of attack. The aim of this study was to evaluate the feasibility and potential benefits of an "extended" conservative variant of the "standard" endoscopic transorbital approach-termed "open-door"-to enhance the exposure of lesions affecting the paramedian aspect of the anterior and middle cranial fossae. METHODS: First, the authors described the technical nuances of the open-door extended transorbital approach (ODETA). Next, they documented its morphometric advantages over standard SETOA. Finally, they provided a clinical-anatomical application to demonstrate enhanced exposure and better angles of attack to treat lesions occupying the paramedian anterior and middle cranial fossae. Five adult cadaveric specimens (10 sides) initially underwent standard SETOA and then extended open-door SETOA (ODETA to the paramedian anterior and middle fossae). The adjunct of hinge-orbitotomy, through three surgical steps and straddling the frontozygomatic suture, converted conventional SETOA to its extended open-door variant. CT scans were performed before dissection and uploaded to the neuronavigation system for quantitative analysis. The angles of attack on the axial plane that addressed four key landmarks, namely the tip of the anterior clinoid process (ACP), foramen rotundum (FR), foramen ovale (FO), and trigeminal impression (TI), were calculated for both operative techniques and compared. RESULTS: Hinge-orbitotomy of the extended open-door SETOA resulted in several surgical, functional, and esthetic advantages: it provided wider axial angles of attack for each of the target points, with a gain angle of 26.68° ± 1.31° for addressing the ACP (p < 0.001), 29.50° ± 2.46° for addressing the FR (p < 0.001), 19.86° ± 1.98° for addressing the FO (p < 0.001), and 17.44° ± 2.21° for addressing the lateral aspect of the TI (p < 0.001), while hiding the skin scar, avoiding temporalis muscle dissection, preserving flap vascularization, and decreasing the rate of bone infection and degree of orbital content retraction. CONCLUSIONS: The extended open-door technique may be specifically suited for selected patients affected by paramedian anterior and middle fossae lesions, with prevalent anteromedial extension toward the anterior clinoid, the foremost compartment of the cavernous sinus and FR and not completely controlled with the pure endoscopic transorbital approach.

[Short-term quality of life assessment after sinus surgery for chronic rhinosinusitis]. / Kurzfristige Lebensqualitätsbewertung nach Nasennebenhöhlenoperation bei chronischer Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) has a negative impact on health-related quality of life (HRQoL). Functional endoscopic sinus surgery (FESS) is the treatment of choice for those not responding to medical treatments. To date, the short-term effects of FESS on HRQoL are still unclear. OBJECTIVE: Evaluation of the short-term effects of FESS on HRQoL in CRS patients using the SNOT-22 questionnaire. METHODS: The results of the validated German version of the Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire were analysed from 89 patients with CRS before surgery and 10-14 days (n = 77), four (n = 77), six weeks (n = 76) and 6 months (n = 71) after FESS, and compared with those of 1,000 healthy controls selected using a non-probability quota sample in accordance to the distribution of the German Microcensus. RESULTS: Compared to the preoperative mean SNOT-22 score (47.35), CRS patients significantly improved in HRQoL 10-14 days (31.75, p < 0.01), 4 weeks (25.84, p < 0.01), 6 weeks (24.16, p < 0.01) and 6 months after FESS (27.16, p < 0.01). Pre- and 6 months postoperatively, the five most important SNOT-22 items were nasal obstruction, smell and taste reduction, thick, mucous nasal secretions, need to blow the nose and postnasal drip. At the 2, 4 and 6-week follow-up, the reduction in smell and taste was most frequently perceived as limiting the HRQoL. CONCLUSIONS: This follow-up study shows for the first time that the reduction in smell and taste should be treated and controlled concervatively in the short term after FESS.

A Magnetic Resonance Imaging-Chemical Exchange Saturation Transfer (MRI-CEST) Method for the Detection of Water Cycling across Cellular Membranes.

Water cycling across the membrane transporters is considered a hallmark of cellular metabolism and it could be of high diagnostic relevance in the characterization of tumors and other diseases. The method relies on the response of intracellular proton exchanging molecules to the presence of extracellular Gd-based contrast agents (GBCAs). Paramagnetic GBCAs enhances the relaxation rate of water molecules in the extracellular compartment and, through membrane exchange, the relaxation enhancement is transferred to intracellular molecules. The effect is detected at the MRI-CEST (Magnetic Resonance Imaging - Chemical Exchange Saturation Transfer) signal of intracellular proton exchanging molecules. The magnitude of the change in the CEST response reports on water cycling across the membrane. The method has been tested on Red Blood Cells and on orthotopic murine models of breast cancer with different degree of malignancy (4T1, TS/A and 168FARN). The distribution of voxels reporting on membrane permeability fits well with the cells' aggressiveness and acts as an early reporter to monitor therapeutic treatments.

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.

Can patient-reported outcomes and inflammatory markers define endotype 2 in chronic rhinosinusitis without nasal polyps?

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease at the clinical phenotype level (without nasal polyp [CRSsNP] vs with nasal polyp [CRSwNP]) and at the underlying inflammatory endotype level (type 2 vs non-type 2). Whether the endotype is associated with clinical presentation in patients with CRSsNP has yet to be explored in detail. OBJECTIVE: To identify associations between endotypes and their clinical significance in patients with CRSsNP based on tissue interleukin-5 levels. METHODS: A total of 104 patients with CRSsNP who underwent functional endoscopic sinus surgery between 2013 and 2017 were endotyped. We collected immunologic and clinical parameters and evaluated whether there were associations between the endotype and clinical features using Visual Analog Scale (VAS), Sino-Nasal Outcome Test-22 (SNOT-22), Sniffin' Sticks test, Lund-Mackay CT score, and nasal endoscopy. RESULTS: Mean tissue interleukin-5 levels were used to identify type 2 inflammation (non-type 2: 3.37 vs type 2: 191.98 pg/g tissue; P < .001). There were no significant clinical differences measured by patient-reported outcome measures between patients with type 2 CRSsNP and those with non-type 2 CRSsNP preoperatively. Type 2 and non-type 2 CRSsNP did not differentiate in CT score, Sniffin' Sticks test, and nasal endoscopy. Postoperative SNOT-22 and VAS scores correlated well with each other (r = 0.75; P < .01). Postoperative VAS scores were in both groups significantly lower than before the operation (type 2: 5.07 vs 2.99; P < .01; non-type 2: 5.74 vs 3.22; P < .01), but not associated to the inflammatory subtype. CONCLUSION: The type of inflammation does not affect the symptoms, the computed tomography scan, or the postoperative results in CRSsNP in contrast to former findings in CRSwNP. TRIAL REGISTRATION: Belgian registration number (B.U.N.) No. B6702020000097.

The visual encoding of graspable unfamiliar objects.

We explored by eye-tracking the visual encoding modalities of participants (N = 20) involved in a free-observation task in which three repetitions of ten unfamiliar graspable objects were administered. Then, we analysed the temporal allocation (t = 1500 ms) of visual-spatial attention to objects' manipulation (i.e., the part aimed at grasping the object) and functional (i.e., the part aimed at recognizing the function and identity of the object) areas. Within the first 750 ms, participants tended to shift their gaze on the functional areas while decreasing their attention on the manipulation areas. Then, participants reversed this trend, decreasing their visual-spatial attention to the functional areas while fixing the manipulation areas relatively more. Crucially, the global amount of visual-spatial attention for objects' functional areas significantly decreased as an effect of stimuli repetition while remaining stable for the manipulation areas, thus indicating stimulus familiarity effects. These findings support the action reappraisal theoretical approach, which considers object/tool processing as abilities emerging from semantic, technical/mechanical, and sensorimotor knowledge integration.

The "Little Circles Test" (LCT): a dusted-off tool for assessing fine visuomotor function.

BACKGROUND: The fine visuomotor function is commonly impaired in several neurological conditions. However, there is a scarcity of reliable neuropsychological tools to assess such a critical domain. AIMS: The aim of this study is to explore the psychometric properties and provide normative data for the Visual-Motor Speed and Precision Test (VMSPT). RESULTS: Our normative sample included 220 participants (130 females) aged 18-86 years (mean education = 15.24 years, SD = 3.98). Results showed that raw VMSPT scores were affected by higher age and lower education. No effect of sex or handedness was shown. Age- and education-based norms were provided. VMSPT exhibited weak-to-strong correlations with well-known neuropsychological tests, encompassing a wide range of cognitive domains of clinical relevance. By gradually intensifying the cognitive demands, the test becomes an indirect, performance-oriented measure of executive functioning. Finally, VMSPT seems proficient in capturing the speed-accuracy trade-off typically observed in the aging population. CONCLUSIONS: This study proposes the initial standardization of a versatile, time-efficient, and cost-effective neuropsychological tool for assessing fine visuomotor coordination. We propose renaming the VMSPT as the more approachable "Little Circles Test" (LCT).

Does a closed reduction improve aesthetical and functional outcome after nasal fracture?

BACKGROUND AND PURPOSES: How closed reduction (CR) to repair a nasal fracture affects the patient's quality of life (QoL) has not been investigated. Here, we assessed QoL before and after CR using disease-specific questionnaires and compared the QoL scores of patients with nasal fractures with normative scores from a reference cohort. METHODS: This was a prospective study of 96 patients with nasal fractures undergoing CR. Patients were interviewed about aesthetic, functional, and QoL issues before and after surgery using the Functional Rhinoplasty Outcome Inventory (FROI-17) and the Rhinoplasty Outcome Evaluation (ROE). Photographs of the nasal area were taken before and after surgery and reviewed. Data were compared with those from a reference cohort (n = 1000). RESULTS: Most fractures were type I (80.6%) and most were caused by sport-related accidents (36.5%). The ROE scores increased from 67.3 preoperatively to 73.4 postoperatively (p = 0.001). The FROI-17 also improved, indicating the overall effect of the nose on QoL (p = 0.002). Compared with the reference cohort, patients felt more affected by nasal symptoms before surgery (- 9.37, p = 0.02) than by more general aspects. ROE scores returned to normative values after surgery (p < 0.001). The postoperative cohort had lower scores for the FROI-17 item overall effects of the nose on QoL than the reference cohort did, although the nasal symptom score remained higher in patients than in reference controls. CONCLUSIONS: This study showed that CR can improve the aesthetical but not the functional outcome of the nose.

A Two-Step Feature Selection Radiomic Approach to Predict Molecular Outcomes in Breast Cancer.

Breast Cancer (BC) is the most common cancer among women worldwide and is characterized by intra- and inter-tumor heterogeneity that strongly contributes towards its poor prognosis. The Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER2), and Ki67 antigen are the most examined markers depicting BC heterogeneity and have been shown to have a strong impact on BC prognosis. Radiomics can noninvasively predict BC heterogeneity through the quantitative evaluation of medical images, such as Magnetic Resonance Imaging (MRI), which has become increasingly important in the detection and characterization of BC. However, the lack of comprehensive BC datasets in terms of molecular outcomes and MRI modalities, and the absence of a general methodology to build and compare feature selection approaches and predictive models, limit the routine use of radiomics in the BC clinical practice. In this work, a new radiomic approach based on a two-step feature selection process was proposed to build predictors for ER, PR, HER2, and Ki67 markers. An in-house dataset was used, containing 92 multiparametric MRIs of patients with histologically proven BC and all four relevant biomarkers available. Thousands of radiomic features were extracted from post-contrast and subtracted Dynamic Contrast-Enanched (DCE) MRI images, Apparent Diffusion Coefficient (ADC) maps, and T2-weighted (T2) images. The two-step feature selection approach was used to identify significant radiomic features properly and then to build the final prediction models. They showed remarkable results in terms of F1-score for all the biomarkers: 84%, 63%, 90%, and 72% for ER, HER2, Ki67, and PR, respectively. When possible, the models were validated on the TCGA/TCIA Breast Cancer dataset, returning promising results (F1-score = 88% for the ER+/ER- classification task). The developed approach efficiently characterized BC heterogeneity according to the examined molecular biomarkers.

Advances in chronic rhinosinusitis in 2020 and 2021.

Major progress has been achieved in the understanding and clinical practice of chronic rhinosinusitis, with or without nasal polyps. These advances resulted in a better understanding of the pathophysiology, the distribution into subgroups, and consequently in a better management perspective using classical approaches and biologics. Pathomechanisms, endotypes and biomarkers, and finally innovative therapeutic approaches are themes especially for the more severe forms of chronic rhinosinusitis, those with uncontrolled severe nasal polyps. Biologicals against key type 2 cytokines are gaining ground in the long-term treatment approaches of often recurrent nasal polyps, and should be integrated in care pathways making use of classical and innovative treatment pathways. These areas of interest show a fast development and will profoundly change our disease management within a decade.

The Area Prostriata may play a role in technical reasoning.

Most recent research indicated how technical reasoning (TR), namely, a specific form of causal reasoning aimed at understanding the physical world, may support the development of tools and technologies of increasing complexity. We have recently identified the Area PF of the left inferior parietal lobe (PF) as a critical structural correlate of TR, as assessed by using two ad-hoc psycho-technical tests evaluating the two main aspects of TR, i.e., physical world's understanding and visuospatial imagery. Here, we extended our findings by implementing new ad-hoc analyses of our previous data by using a whole-brain approach. Results showed that the cortical thickness (CT) of the left Area Prostriata of the visual cortex, alongside the left Area PF CT, predicts TR performance.

Reboot surgery for chronic rhinosinusitis with nasal polyposis: recurrence and smell kinetics.

OBJECTIVE: To evaluate the time for recovery of the sense of smell in patients with CRSwNP who underwent Reboot surgery compared to patients undergoing ESS in a long-term follow-up study. METHODS: Data were collected retrospectively from 168 patients with severe uncontrolled CRSwNP, who underwent revision surgery, either as Extended Endoscopic Sinus Surgery (Reboot, 140 patients) or as regular Endoscopic Sinus Surgery (ESS, 28 patients) between January 1, 2014, and December 31, 2015, aiming to compare the outcome of surgeries after 2 years of follow-up. Sense of smell was scored as judged by the patient using scores 0 to 3 reflecting a percentage estimate of remaining smell. RESULTS: Smell improved similarly in the Reboot and ESS groups over the first 9 months, which was maintained over 24 months in the Reboot, but not the ESS group (p = 0.007 after 18 months, p = 0.001 after 24 months). Furthermore, polyp recurrence rates were significantly lower in the Reboot group. CONCLUSION: Reboot surgery significantly improved olfactory function and significantly reduced nasal polyp recurrence rates over 2 years post-operatively. Therefore, Reboot should be considered for patients with uncontrolled severe CRSwNP, specifically when ESS failed, to offer long-term smell and a polyp-free status. LEVEL OF EVIDENCE: 3b.

Diagnostic performance of nasal cytology.

PURPOSE: Nasal pathologies are characterized by a symptomatology that hardly allows to distinguish allergic rhinitis (AR), non-allergic rhinitis (NAR), and chronic rhinosinusitis (CRS). Nasal cytology (NC) has shown increasing importance in helping the clinician to differentiate the various phenotypes of rhinitis. NC allows us to evaluate nasal cellularity by distinguishing AR and various types of NAR. The objective of the study is to assess the diagnostic performance of the NC by evaluating its sensitivity, specificity, and predictive value. METHODS: We recruited 387 patients with persistent rhinitis symptoms, and nasal cytology was performed. The rhinocytogram was obtained by reading for fields and the cellular count was made using quantitative and semi-quantitative grading together. RESULTS: Two hundred and fifteen patients (55.5%; 38 had acute rhinitis, 24 acute sinusitis, 153 chronic rhinosinusitis) out of 387 referred nasal symptoms. Cytological specimen showed a mean of 94 ± 4% ciliated cells, 29 ± 0.2% mucinous cells, 16 ± 0.1% neutrophils, 11 ± 0.08% eosinophils, 4 ± 0.03 lymphocytes, 4 ± 0.03% mast cells, and 4 ± 0.01% other cells. NC was positive in 271 cases (70%). After revision of medical history, 153 patients (39%) were considered positive for NAR. Test sensibility was 100% (95% CI 97-100), specificity was 49.6% (95% CI 43-56%). Positive predictive value (PPV) was 56% (95% CI 50-62%), and negative predictive value (NPV) was 100% (95% CI 96-100%). The positive likelihood ratio was 1.98 (95% CI 1.75-2.25). Accuracy of the test was 69.5% (95% CI 64.6-74.0%). CONCLUSION: Our data showed ability to identify the true-positive patients with NAR but a low ability to identify the true-negative patients, with a global accuracy of 69.5%.

Correlation between olfactory function, age, sex, and cognitive reserve index in the Italian population.

PURPOSE: Loss of smell decreases the quality of life and contributes to the failure in recognizing hazardous substances. Given the relevance of olfaction in daily life, it is important to recognize an undiagnosed olfactory dysfunction to prevent these possible complications. Up to now, the prevalence of smell disorders in Italy is unknown due to a lack of epidemiological studies. Hence, the primary aim of this study was to evaluate the prevalence of olfactory dysfunction in a sample of Italian adults. METHODS: Six hundred and thirty-three participants (347 woman and 286 men; mean age 44.9 years, SD 17.3, age range 18-86) were recruited from 10 distinct Italian regions. Participants were recruited using a convenience sapling and were divided into six different age groups: 18-29 years (N = 157), 30-39 years (N = 129), 40-49 years (N = 99), 50-59 years (N = 106), > 60 years (N = 142). Olfactory function, cognitive abilities, cognitive reserve, and depression were assessed, respectively, with: Sniffin' Sticks 16-item Odor Identification Test, Montreal Cognitive Assessment, Cognitive Reserve Index, and the Beck Depression Inventory. Additionally, socio-demographic data, medical history, and health-related lifestyle information were collected. RESULTS: About 27% of participants showed an odor identification score < 12 indicating hyposmia. Multiple regression analysis revealed that OI was significantly correlated with age, sex, and cognitive reserve index, and young women with high cognitive reserve index showing the highest olfactory scores. CONCLUSION: This study provides data on the prevalence of olfactory dysfunction in different Italian regions.

EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis; it is typically characterized by a type 2 inflammatory reaction and by comorbidities, including asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, and allergies. Here, the European Forum for Research and Education in Allergy and Airway Diseases proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinical practice. A rational approach for the treatment of uncontrolled severe CRSwNP is discussed; it consists of evaluating the perspective and risks of surgery and efficacy and adverse events of biologics on the basis of currently available data. Further, possible combinations of surgery and biologics are discussed, and a rationale is provided. Here, it is of importance to adequately counsel the patient about both approaches to enable a decision-making process with an informed patient. Criteria for the selection of a biologic drug are provided, as several biologics for uncontrolled severe CRSwNP will be available in many countries within a short time. Further, suggestions for monitoring of the drug effects that support recognition of responders to the therapy and, subsequently, the decision regarding continuation or discontinuation of the biologic are proposed.

Clinical connectome fingerprints of cognitive decline.

Brain connectome fingerprinting is rapidly rising as a novel influential field in brain network analysis. Yet, it is still unclear whether connectivity fingerprints could be effectively used for mapping and predicting disease progression from human brain data. We hypothesize that dysregulation of brain activity in disease would reflect in worse subject identification. We propose a novel framework, Clinical Connectome Fingerprinting, to detect individual connectome features from clinical populations. We show that "clinical fingerprints" can map individual variations between elderly healthy subjects and patients with mild cognitive impairment in functional connectomes extracted from magnetoencephalography data. We find that identifiability is reduced in patients as compared to controls, and show that these connectivity features are predictive of the individual Mini-Mental State Examination (MMSE) score in patients. We hope that the proposed methodology can help in bridging the gap between connectivity features and biomarkers of brain dysfunction in large-scale brain networks.

Mepolizumab Effectiveness and Allergic Status in Real Life.

BACKGROUND: It is not clear whether mepolizumab is differently effective in allergic and nonallergic severe eosinophilic asthmatics (SEA) in real life. OBJECTIVE: We tested mepolizumab effectiveness in allergic/nonallergic SEA in real life. A strict criterion to identify the 2 phenotypes was used. METHOD: We retrospectively considered 134 consecutive patients divided into allergic, with a positivity to at least 1 allergen to prick tests and/or IgE values ≥100 UI/mL (severe allergic eosinophilic asthma [SAEA]; n: 97-72.4%), and nonallergic, with no prick test results and normal IgE levels <100 UI/mL (severe nonallergic eosinophilic asthma [SNAEA]; n: 37-27.6%). They had taken mepolizumab for at least 6 months. RESULTS: After 10.9 ± 3.7 months, improvements in FEV1%, FEF25-75%, exacerbation numbers, blood eosinophil (BE) counts, fractional exhaled nitric oxide (FENO) (ppb), percentages of patients that stopped/reduced short-acting ß2-agonists (SABAs) or oral corticosteroid (OC), observed after treatment, were similar in both groups. Only Asthma Control Test (ACT) increases were higher in SNAEA (8 [5-9]) than in SAEA (5 [2.5-8.5]; p = 0.016). However, no differences were found after treatment in percentages of subjects with ACT ≥20, as well as with FEV1 >80%, FEF25-75 >65%, exacerbations ≤2, BE <300 cells/µL, and FENO <25 ppb between SAEA and SNAEA. Besides, no significant relationships were found, comparing SNAEA with SAEA, for FEV1% (ß = -0.110; p = 0.266), FEF25-75% (ß = -0.228; p = 0.06), BE counts (ß = -0.012; p = 0.918), FENO (ß = 0.234; p = 0.085), ACT (ß = 0.046; p = 0.660), and exacerbations (ß = -0.070; p = 0.437). No different associations between lung function and SNAEA occurrence when compared to SAEA condition (FEV1 >80%: OR = 1.04 [95% CI: 0.43-2.55], p = 0.923; FEF25-75 >65%: OR = 0.41 [95% CI: 0.08-2.03], p = 0.272) were detected. Neither all other parameters, such as ACT >20 (OR = 0.73 [95% CI: 0.32-1.63], p = 0.440), presence of exacerbations (OR = 1.35 [95% CI: 0.55-3.27], p = 0.512), SABA discontinuation (OR = 1.16 [95% CI: 0.40-3.39], p = 0.790), and OC cessation/reduction (OR = 3.44 [95% CI: 0.40-29.27], p = 0.258), were differently associated with 1 or the other phenotype. CONCLUSION: Mepolizumab can be considered as a valid therapeutic choice for either allergic or nonallergic SEA in real life.