Development of machine learning models to predict papillary carcinoma in thyroid nodules: The role of immunological, radiologic, cytologic and radiomic features.

OBJECTIVE: Approximately 30 % of thyroid nodules yield an indeterminate diagnosis through conventional diagnostic strategies. The aim of this study was to develop machine learning (ML) models capable of identifying papillary thyroid carcinomas using preoperative variables. METHODS: Patients with thyroid nodules undergoing thyroid surgery were enrolled in a retrospective monocentric study. Six 2-class supervised ML models were developed to predict papillary thyroid carcinoma, by sequentially incorporating clinical-immunological, ultrasonographic, cytological, and radiomic variables. RESULTS: Out of 186 patients, 92 nodules (49.5 %) were papillary thyroid carcinomas in the histological report. The Area Under the Curve (AUC) ranged from 0.41 to 0.61 using only clinical-immunological variables. All ML models exhibited an increased performance when ultrasound variables were included (AUC: 0.95-0.97). The addition of cytological (AUC: 0.86-0.97) and radiomic (AUC: 0.88-0.97) variables did not further improve ML models' performance. CONCLUSION: ML algorithms demonstrated low accuracy when trained with clinical-immunological data. However, the inclusion of radiological data significantly improved the models' performance, while cytopathological and radiomics data did not further improve the accuracy. LEVEL OF EVIDENCE: Level 4.

The Use of Artificial Intelligence in Head and Neck Cancers: A Multidisciplinary Survey.

Artificial intelligence (AI) approaches have been introduced in various disciplines but remain rather unused in head and neck (H&N) cancers. This survey aimed to infer the current applications of and attitudes toward AI in the multidisciplinary care of H&N cancers. From November 2020 to June 2022, a web-based questionnaire examining the relationship between AI usage and professionals' demographics and attitudes was delivered to different professionals involved in H&N cancers through social media and mailing lists. A total of 139 professionals completed the questionnaire. Only 49.7% of the respondents reported having experience with AI. The most frequent AI users were radiologists (66.2%). Significant predictors of AI use were primary specialty (V = 0.455; p < 0.001), academic qualification and age. AI's potential was seen in the improvement of diagnostic accuracy (72%), surgical planning (64.7%), treatment selection (57.6%), risk assessment (50.4%) and the prediction of complications (45.3%). Among participants, 42.7% had significant concerns over AI use, with the most frequent being the 'loss of control' (27.6%) and 'diagnostic errors' (57.0%). This survey reveals limited engagement with AI in multidisciplinary H&N cancer care, highlighting the need for broader implementation and further studies to explore its acceptance and benefits.

Image-Guided Intraoperative Assessment of Surgical Margins in Oral Cavity Squamous Cell Cancer: A Diagnostic Test Accuracy Review.

(1) Background: The assessment of resection margins during surgery of oral cavity squamous cell cancer (OCSCC) dramatically impacts the prognosis of the patient as well as the need for adjuvant treatment in the future. Currently there is an unmet need to improve OCSCC surgical margins which appear to be involved in around 45% cases. Intraoperative imaging techniques, magnetic resonance imaging (MRI) and intraoral ultrasound (ioUS), have emerged as promising tools in guiding surgical resection, although the number of studies available on this subject is still low. The aim of this diagnostic test accuracy (DTA) review is to investigate the accuracy of intraoperative imaging in the assessment of OCSCC margins. (2) Methods: By using the Cochrane-supported platform Review Manager version 5.4, a systematic search was performed on the online databases MEDLINE-EMBASE-CENTRAL using the keywords "oral cavity cancer, squamous cell carcinoma, tongue cancer, surgical margins, magnetic resonance imaging, intraoperative, intra-oral ultrasound". (3) Results: Ten papers were identified for full-text analysis. The negative predictive value (cutoff < 5 mm) for ioUS ranged from 0.55 to 0.91, that of MRI ranged from 0.5 to 0.91; accuracy analysis performed on four selected studies showed a sensitivity ranging from 0.07 to 0.75 and specificity ranging from 0.81 to 1. Image guidance allowed for a mean improvement in free margin resection of 35%. (4) Conclusions: IoUS shows comparable accuracy to that of ex vivo MRI for the assessment of close and involved surgical margins, and should be preferred as the more affordable and reproducible technique. Both techniques showed higher diagnostic yield if applied to early OCSCC (T1-T2 stages), and when histology is favorable.

Multiple Cutaneous Manifestations in ANCA-Positive Eosinophilic Granulomatosis with Polyangiitis before and after Biologic Therapy: Clinical and Histopathologic Characterization of a Paradigmatic Case.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare immune-mediated vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Having systemic and possibly severe involvement, a prompt recognition of its clinical features is crucial to achieve favorable patient outcomes. Although cutaneous manifestations represent key elements, these still remain poorly characterized. We report a case of ANCA-positive EGPA presenting with palpable purpura, livedo reticularis, and pemphigoid-like lesions that was successfully treated with glucocorticoid therapy and rituximab. This report portrays the evolution of cutaneous lesions in ANCA-positive EGPA and demonstrates how dermatologic signs may represent indicators of active disease, allowing for timely diagnosis and for the monitoring of disease activity during treatment.

Dupilumab facial redness: histologic characterization on a series of four cases.

Dupilumab-related head and neck dermatitis is an increasingly reported clinical manifestation occurring in 4-10% of patients on dupilumab that was apparently not reported in clinical trials. Out of 62 adult patients treated with dupilumab for atopic dermatitis in the authors' center, four cases (6%) of head and neck dermatitis were observed, for which a skin biopsy was obtained. Onset occurred between 8 and 24 weeks after initiation of dupilumab, and the reaction resolved after 8-12 weeks. Histopathology and immunohistochemical findings support the authors' hypothesis that facial redness may be a toxic effect induced by dupilumab, although its pathogenesis still requires further investigation.

Plain language summary Dupilumab is an advanced treatment for atopic dermatitis. The new appearance of a peculiar head and neck dermatitis may be observed in as many as 4­10% of subjects receiving this drug, though it was not reported in the course of the clinical trials that led to the approval of dupilumab. Out of 62 adults treated with dupilumab for atopic dermatitis in the authors' Dermatology Clinic, four subjects (6%) were observed to have head and neck dermatitis. The condition appeared between 8 and 24 weeks after initiation of dupilumab and lasted 8­12 weeks. The four subjects gave permission to perform a skin biopsy. Microscopic analysis of their samples suggested that this peculiar facial redness may be a drug-induced reaction associated with dupilumab, although its causes and mechanisms still require understanding.

Impact of COVID-19 on patients with atopic dermatitis.

Data on the tolerability and response to biologic therapies for type 2 immune disorders in the context of coronavirus disease 2019 (COVID-19) are currently lacking. Our survey aimed at assessing the adherence of patients to dupilumab therapy and the risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 80 patients with atopic dermatitis treated with dupilumab completed a web-based survey. Of the 80 patients, 7 discontinued dupilumab owing to concerns and difficulties related to COVID-19. Our sample was highly susceptible to viral infection owing to the frequency of risk factors including living in high SARS-CoV-2 burden areas, such as in Northern Italy; having comorbidities, such as asthma, diabetes, and cardiovascular disease; and being of advanced age. Older patients in our sample are particularly exposed to the risk of COVID-19-related cytokine storm, triggered by excessive interleukin-4 production and type 2 immune response. One patient contracted SARS-CoV-2 infection without the progression of COVID-19 despite continuing scheduled dupilumab treatment. Because evidence on the appropriate management of biologic therapy in the setting of COVID-19 is lacking, the collection of clinical data from patients in treatment with dupilumab is a valuable addition to current clinical practice. Our survey provides a contribution to the understanding of the tolerability and response to dupilumab during COVID-19 and suggests a feasible and effective approach to patients being treated with biologics even when social distancing is required.

Network Analysis Integrating microRNA Expression Profiling with MRI Biomarkers and Clinical Data for Prostate Cancer Early Detection: A Proof of Concept Study.

The MRI of the prostate is the gold standard for the detection of clinically significant prostate cancer (csPCa). Nonetheless, MRI still misses around 11% of clinically significant disease. The aim was to comprehensively integrate tissue and circulating microRNA profiling, MRI biomarkers and clinical data to implement PCa early detection. In this prospective cohort study, 76 biopsy naïve patients underwent MRI and MRI directed biopsy. A sentinel sample of 15 patients was selected for a pilot molecular analysis. Weighted gene coexpression network analysis was applied to identify the microRNAs drivers of csPCa. MicroRNA-target gene interaction maps were constructed, and enrichment analysis performed. The ANOVA on ranks test and ROC analysis were performed for statistics. Disease status was associated with the underexpression of the miRNA profiled; a correlation was found with ADC (r = -0.51, p = 0.02) and normalized ADC values (r = -0.64, p = 0.002). The overexpression of miRNAs from plasma was associated with csPCa (r = 0.72; p = 0.02), and with PI-RADS assessment score (r = 0.73; p = 0.02); a linear correlation was found with biomarkers of diffusion and perfusion. Among the 800 profiled microRNA, eleven were identified as correlating with PCa, among which miR-548a-3p, miR-138-5p and miR-520d-3p were confirmed using the RT-qPCR approach on an additional cohort of ten subjects. ROC analysis showed an accuracy of >90%. Provided an additional validation set of the identified miRNAs on a larger cohort, we propose a diagnostic paradigm shift that sees molecular data and MRI biomarkers as the prebiopsy triage of patients at risk for PCa. This approach will allow for accurate patient allocation to biopsy, and for stratification into risk group categories, reducing overdiagnosis and overtreatment.

The future direction of imaging in prostate cancer: MRI with or without contrast injection.

BACKGROUND: Multiparametric MRI (mpMRI) is the "state of the art" management tool for patients with suspicion of prostate cancer (PCa). The role of non-contrast MRI is investigated to move toward a more personalized, less invasive, and highly cost-effective PCa diagnostic workup. OBJECTIVE: To perform a non-systematic review of the existing literature to highlight strength and flaws of performing non-contrast MRI, and to provide a critical overview of the international scientific production on the topic. MATERIALS AND METHODS: Online databases (Medline, PubMed, and Web of Science) were searched for original articles, systematic review and meta-analysis, and expert opinion papers. RESULTS: Several investigations have shown comparable diagnostic accuracy of biparametric (bpMRI) and mpMRI for the detection of PCa. The advantage of abandoning contrast-enhanced sequences improves operational logistics, lowering costs, acquisition time, and side effects. The main limitations of bpMRI are that most studies comparing non-contrast with contrast MRI come from centers with high expertise that might not be reproducible in the general community setting; besides, reduced protocols might be insufficient for estimation of the intra- and extra-prostatic extension and regional disease. The mentioned observations suggest that low-quality mpMRI for the general population might represent the main shortage to overcome. DISCUSSION: Non-contrast MRI future trends are likely represented by PCa screening and the application of artificial intelligence (AI) tools. PCa screening is still a controversial topic; bpMRI has become one of the most promising diagnostic applications, as it is a more sensitive test for PCa early detection, compared to serum PSA level test. Also, AI applications and radiomic have been the object of several studies investigating PCa detection using bpMRI, showing encouraging results. CONCLUSION: Today, the accessibility to MRI for early detection of PCa is a priority. Results from prospective, multicenter, multireader, and paired validation studies are needed to provide evidence supporting its role in the clinical practice.

Potential clinical and serological predictors of chronic spontaneous urticaria relapse in patients under omalizumab treatment.

Background: Omalizumab is not considered a disease-modifying drug and, accordingly, a large proportion of patients experience a relapse following withdrawal from treatment. Patients & methods: A total of 42 patients who underwent at least one cycle of treatment with omalizumab were enrolled. Two groups of relapsed and not-relapsed subjects were compared. Then, patients were divided into subgroups. Results: Female patients relapse more frequently than male subjects. Patients who relapsed complained a long duration of disease, while patients who did not relapse had short a history of disease. Very early responders are thought to have a high recurrence rate. Basal IgE levels were increased in early responders and cholesterol levels were high in very early responders, who relapse following withdrawal from omalizumab. High D-dimer levels were observed in late responders. Conclusion: The identification of clinical and serological predictors will play a pivotal role in the future management of patients treated with omalizumab.

Atopic dermatitis in the elderly Caucasian population: diagnostic clinical criteria and review of the literature.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing eczematous dermatitis typically affecting young patients in a percentage from 15 to 20%; although it typically affects young people and adults, recent papers highlighted the emerging of the disease in the elderly population. METHODS: The aim of the study was to identify the clinical criteria and allergic sensitization that may be able to support physicians and dermatologists in making a correct diagnosis of AD in the elderly. The second aim of this study was to investigate the incidence, the main features, the gender prevalence, the immunological profile, and comorbidities characterizing patients older than 65 years affected by AD. RESULTS: Based on clinical and serological patterns, different phenotypes of AD were identified: generalized AD (55%) characterized by eczematous lesions involving typical areas of the body or prurigo nodularis-like AD; chronic eczematous hand dermatitis (23%); face and neck involvement (9%); and nummular eczema (13%). Skin prick tests revealed a positivity for aeroallergens in 49.6% of patients, most of them being polysensitized (55%). Additionally, food skin prick tests were positive in 25% of patients. Most of the patients reported comorbidities, particularly IgE-mediated diseases, such as seasonal rhino-conjunctivitis, asthma, and chronic obstructive pulmonary disease. Gastrointestinal symptoms such as meteorism, dyspepsia, cramps/abdominal pain, and diarrhea/constipation, were observed in 35% of patients consequent to food allergy. CONCLUSION: In our study, we suggest clinical and serological criteria that may be able to guide in the diagnosis of AD in Caucasian elderly, and to design an appropriate treatment according to the current standard protocol.

Utilization of imaging for staging in bladder cancer: is there a role for MRI or PET-computed tomography?

PURPOSE OF REVIEW: Accurate staging of bladder cancer is essential to guide appropriate management. In this review, we discuss the principles, applications and performance of multiparametric MRI (mpMRI) and PET-computer tomography (PET-CT) for local and distant staging of bladder cancer. RECENT FINDINGS: Bladder mpMRI has a high diagnostic performance in local staging of bladder cancer, superior to other imaging modalities. It can accurately differentiate muscle invasive bladder cancer (MIBC) from non-MIBC (NMIBC), as well as ≤T2 from ≥T3 stages. mpMRI can be used to assess pelvic lymph nodes, although its sensitivity is relatively low. For the assessment of the upper urinary tract, CT urography is the imaging modality of choice. magnetic resonance urography is a viable alternative to CT in selected cases. Although PET-CT is accurate for nodal and distant staging of bladder cancer, there is no clear evidence on its superior diagnostic performance compared with contrast-enhanced CT. SUMMARY: mpMRI is the most accurate imaging modality for local staging of bladder cancer, capable to accurately distinguish MIBC from NMIBC. Nodal and distant staging relies primarily on contrast-enhanced CT.

IFN-γ/IL-6 and related cytokines in chronic spontaneous urticaria: evaluation of their pathogenetic role and changes during omalizumab therapy.

BACKGROUND: Recent studies highlight that high levels of cytokines may precede the onset of many systemic autoimmune disorders and may also be related to chronic spontaneous urticaria (CSU) activity. METHODS: Eight patients with CSU candidate to omalizumab therapy were enrolled. Four healthy controls were included with the purpose of comparing baseline cytokine levels. We evaluated serum levels of IFN-γ, IL-2, 4, 6, 8, and 10, TNF-α, and GM-CSF. For the patient group, venous blood samples were drawn at T0, T1 (1 week after first drug administration), T2 (after 3 months), T3 (after 6 months), and in case of relapse. Cytokine levels were measured using the human cytokines 8-plex kit. Disease activity and effect of therapy were calculated by means of Urticaria Activity Score 7. RESULTS: Higher levels of IL-6 and IFN-γ were found in patients with CSU compared to those observed in the control group. Moreover, a common trend between these cytokines and the clinical history of disease could be hypothesized, with a decrease in levels of IFN-γ and IL-6 following remission of CSU with omalizumab treatment. Levels of other tested cytokines were similar between patients and healthy subjects. CONCLUSION: IFN-γ and IL-6 are proinflammatory cytokines that are strongly related to autoimmunity. Despite being limited by the small sample size, our data offer new insight into a better understanding of the pathogenesis of CSU and support the need for further investigations.