Search Results (4,632)

Background: The increasing use of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with breast cancer has led to a growing number of incidentally detected thyroid lesions. Thyroid incidentaloma refers to a focal area of increased metabolic activity within the thyroid gland. Up to 35% of focal thyroid incidentalomas are malignant. Early detection of thyroid carcinoma may allow less invasive surgical management and reduce the need for more extensive treatment associated with advanced disease, including total thyroidectomy, neck dissection, and radioactive iodine therapy. The objective of this study was to estimate the prevalence of focal thyroid incidentaloma and incidental thyroid carcinoma detected on PET/CT scans performed in breast cancer patients at a single tertiary medical center serving a highly ethnically diverse population. Methods: Medical records and PET/CT scans were retrospectively reviewed at a single medical center. Data collected included the presence of thyroid incidentaloma, maximum standardized uptake value (SUVmax), thyroid cytology, primary malignancy type, breast cancer status, ethnicity, and age. A total of 1233 patients with cancer who underwent PET/CT imaging and received treatment at ZIV Medical Center between August 2018 and December 2024 were included. Forty-two patients with primary thyroid carcinoma or head and neck carcinoma were excluded. Patients were categorized into breast cancer and non-breast cancer groups and compared regarding the prevalence of thyroid incidentaloma, referral rates for further evaluation by head and neck specialists, and the rate of incidental thyroid carcinoma. Results: Among 330 patients with breast cancer, 16 (4.8%) had a focal incidental thyroid finding, compared with 24 (2.8%) of 861 patients with non-breast malignancies who underwent PET/CT imaging. Among the 16 breast cancer patients with thyroid incidentaloma, thyroid carcinoma was subsequently confirmed in 4 patients (25%) who underwent further evaluation. The proportion of patients with confirmed thyroid carcinoma among those with incidentalomas was 1.2% (4/330) in the breast cancer group compared with 0.46% (4/861) in the non-breast cancer group. Approximately half of the patients in both groups were referred for further thyroid evaluation. Among breast cancer patients, non-significant trends toward higher referral rates were observed in patients with non-advanced disease, higher SUVs, and Jewish ethnicity. Nearly all patients evaluated by head and neck specialists underwent fine-needle aspiration (FNA). The mean SUV among patients diagnosed with papillary thyroid carcinoma (PTC) on FNA (n = 8; breast and non-breast cancer combined) was 15.2 (IQR: 7.3–17.0), compared with 5.2 (IQR: 5.0–6.0) among patients with benign cytology (n = 5; p = 0.011). Conclusions: Thyroid incidentalomas identified on PET/CT scans in breast cancer patients were relatively common in this cohort, and a proportion of evaluated lesions were subsequently diagnosed as thyroid carcinoma. Referral and diagnostic follow-up rates were variable, with approximately half of patients referred for further evaluation and only one-third attending a head and neck clinic. Given the retrospective design, limited number of biopsy-confirmed cases, and potential verification bias, these findings should be interpreted with caution. Nevertheless, they highlight the importance of clinical awareness and support individualized assessment of PET/CT-detected thyroid incidentalomas rather than broad management recommendations. Full article

Background/Objectives: The mandatory spinal cord stimulation (SCS) trial was established in the era of tonic, paresthesia-dependent stimulation, when pre-implantation outcome prediction was unreliable, validated psychological screening was unavailable, and post-implantation programming options were limited. This narrative review examines whether universal trialing remains justified in the context of contemporary paresthesia-free waveforms, mechanistically informed psychological assessment, and current evidence on the predictive utility of screening trials. The objective was to evaluate the contemporary rationale for selective rather than universal trialing and to propose a structured four-step clinical decision framework integrating contraindication screening, pain phenotype certainty, psychological risk stratification, and centre-level criteria, with the aim of identifying patients in whom a trial is most likely to add prognostic information. Methods: PubMed and the Cochrane Library were searched using predefined search strings. Eligible publications included randomised controlled trials (including the TRIAL-STIM RCT), systematic reviews, registry-based cohort studies, health-economic analyses, and consensus guidelines. Results: The evidence base comprised randomised controlled trials of trial-versus-no-trial strategies, paresthesia-free waveforms, and closed-loop stimulation (including TRIAL-STIM, SENZA-RCT, EVOKE, and ECHO-MAC), together with large registry and cohort studies, systematic reviews, qualitative patient-experience data, and current consensus guidance. Modern paresthesia-free and physiology-guided paradigms reduce several technical functions historically served by trialing, although the extent varies by waveform. The only randomised trial designed specifically to compare trial-first and no-trial strategies (TRIAL-STIM) found no difference in pain outcomes at 6 or 36 months; however, its single healthcare setting and predominantly paresthesia-based waveform mix limit generalisability. Structured pre-implantation psychological evaluation may provide prognostic information that short-duration trialing cannot replicate. At the same time, contemporary guidelines continue to recommend trialing and several clinically relevant arguments for retaining it persist, including patient experiential learning, identification of screening false negatives, and grey-zone decision-making. Conclusions: In carefully selected patients with established neuropathic pain phenotypes and comprehensive pre-implantation evaluation, selective trialing may be clinically reasonable. The proposed four-step framework offers a structured basis for allocating trial stimulation to the patients most likely to benefit from it and should be interpreted as hypothesis-generating pending prospective validation. This review does not advocate abandoning trial stimulation; rather, it argues that its role should be examined within an individualised, phenotype- and risk-stratified pathway. Full article

Introduction: Children with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB), but clinical correlates of polysomnography-derived severity remain incompletely defined. Objectives: This retrospective clinical–polysomnographic cohort study examined associations between selected demographic, anthropometric, cardiac, and otolaryngological variables and SDB severity metrics in children and adolescents with DS. Materials and Methods: Forty-eight participants aged ≤ 18 years underwent overnight polysomnography for suspected SDB. Respiratory events were scored according to paediatric AASM criteria; hypopnoeas required a ≥30% airflow reduction associated with ≥3% oxygen desaturation and/or arousal, and ODI was calculated using ≥3% desaturation events per hour of total sleep time. Outcomes included Apnoea–Hypopnoea Index (AHI), ODI, minimum SpO₂, and time with SpO₂ < 90%. Results: OSA was highly prevalent: AHI ≥ 1 event/h was observed in 93.8% of participants, AHI ≥ 5 events/h in 58.3%, and AHI ≥ 10 events/h in 35.4%. Mean AHI was 10.51 ± 11.82 events/h, and mean ODI was 7.07 ± 9.31 events/h. Age at PSG was not significantly associated with AHI. AHI correlated with ODI, and clinically documented adenoidal hypertrophy correlated with both AHI and ODI. Males showed significantly higher ODI values than females, whereas sex differences in AHI, minimum SpO₂, and time with SpO₂ < 90% were not significant. In exploratory multivariable models, adenoidal hypertrophy was associated with higher ODI, while adenotonsillectomy was associated with lower minimum SpO₂. Conclusions: The association between atrioventricular canal defect and hypoxaemic burden was not robust in bootstrap analyses. These exploratory findings do not warrant changes to current screening management strategies, but support further prospective studies incorporating standardised ENT and cardiac characterisation. Full article

Background/Objectives: Occult cervical nodal metastasis drives prognosis in oral cavity squamous cell carcinoma (OCSCC), yet current tools for risk stratification in clinically node-negative (cN0) patients are imperfect. Machine learning (ML) models have been proposed to refine selection for elective neck dissection (END), but their diagnostic performance and generalizability are unclear. Methods: We performed a diagnostic test accuracy systematic review and meta-analysis of ML models predicting occult nodal metastasis in adults with cN0 OCSCC. Eligible studies evaluated an ML-based model, used pathologic nodal status as the reference standard, and reported or allowed reconstruction of sensitivity and specificity. Internal and external validation were distinguished; quantitative synthesis was restricted to non-overlapping external validation cohorts. Diagnostic performance was synthesized with a bivariate random-effects hierarchical summary receiver operating characteristic (HSROC) model, with prespecified sensitivity analyses restricting to lower-risk patient-selection cohorts, models using only preoperative predictors, and non-outlying cohorts. Results: Thirteen retrospective studies (4730 patients) met inclusion; pooled occult nodal metastasis prevalence was 23.6% (crude 20.4%). Eight studies reported only internal validation; five provided six external validation cohorts. Across these external cohorts, pooled sensitivity was 0.79 (95% CI, 0.64–0.89) and specificity 0.84 (95% CI, 0.70–0.93). Negative predictive values were consistently high (0.94–0.98), whereas positive predictive values were modest (0.39–0.85). Sensitivity analyses yielded similar summary estimates with wider confidence intervals. Conclusions: Externally validated ML models for predicting occult nodal metastasis in cN0 OCSCC show promise but remain insufficiently validated to guide END in routine practice. Full article

Background: The current literature suggests that screening for symptoms of pediatric obstructive sleep-disordered breathing (SDB) is low despite guidelines from the American Academy of Pediatrics to screen all children at well visits. Specific factors that affect screening rates for snoring have not been well delineated. Materials and Methods: This study is a retrospective chart review of children ages 2–12 who presented for well-child visits at an academic hospital network. Multivariable logistic regression was used to identify factors associated with documentation for SDB screening. Results: Of 1001 charts reviewed, 809 children met inclusion criteria (median age 5 IQR [3–8] years, 50.3% female). Less than half (45.4%) of the children were screened for snoring, and 16.1% of those screened had symptoms of SDB. Adjusted multivariable regression showed that screening was significantly higher in older children (OR: 2.19 [1.46–3.29]; p < 0.001 for 5- to less than 8-year-old children; OR: 2.37 [1.57–3.57]; p < 0.001 for 8- to less than 12-year-old children). Children of the Other race group were also found to have significantly lower screening rates than Black and White children (OR 0.44 [0.23–0.84]; p = 0.014). The odds of being screened were 94% lower in visits in which a medical trainee was involved (p < 0.001). The odds of being screened at a well-child visit were 3.7 times higher in encounters in which a templated note was used (p < 0.001). Conclusions: Less than half of the children presenting for well visits were screened for snoring in this cohort. Differences in screening were attenuated by trainee involvement and the use of templated notes, which presents further avenues to explore meeting guideline recommendations for SDB screening. Full article

Background: Endoscopic endonasal approaches for pituitary adenomas are associated with improved clinical and quality of life (QOL) outcomes. However, the necessity of middle turbinate resection to optimize surgical exposure remains controversial, particularly regarding its potential impact on postoperative nasal and tumor-related QOL. Methods: This prospective cohort study included adult patients undergoing endoscopic endonasal transsphenoidal resection of pituitary adenomas between 2014 and 2021 at a tertiary center. Patients were divided into those undergoing bilateral middle turbinectomy and those with turbinate preservation. Tumor-related QOL was assessed using the Anterior Skull Base Disease-Specific Questionnaire (ASBS-Q), and nasal QOL using the Sinonasal Outcome Test-22 (SNOT-22), at baseline and multiple postoperative time points up to >6 months. Clinical and surgical variables were collected and compared between groups. Results: Our study included 73 patients, 51 (69.9.%) of whom underwent middle turbinate resection and 22 (30.1%) who did not. The difference in overall ASBS-Q scores did not alter significantly between both groups during the long-term postoperative course (>6 months). SNOT-22 score differences also did not alter significantly throughout the entire postoperative course. Conclusion: Middle turbinectomy during endoscopic endonasal resection of pituitary adenomas was not associated in our cohort to adversely affect long-term nasal or tumor-related QOL. Full article

Background/Objectives: Machine learning (ML) models have increasingly been applied to prognostic prediction in oral cavity squamous cell carcinoma (OCSCC), though their performance and methodological quality remain variably reported. This systematic review evaluated contemporary ML-based prognostic models for clinically relevant OCSCC outcomes, with emphasis on independently validated studies. Methods: A systematic review was conducted according to PRISMA guidelines using PubMed, Scopus, Cochrane Library, and CINAHL databases through 1 December 2025. Studies evaluating ML or artificial intelligence prognostic models in adult OCSCC patients were included. Outcomes included overall survival, recurrence, disease-free survival, recurrence-free survival, disease-specific survival, cancer-specific survival, progression, and nodal metastasis. Data extraction and risk-of-bias assessment using PROBAST + AI were performed independently by reviewers. Results: Forty studies comprising 105,619 patients met inclusion criteria. ML architectures included random forests, support vector machines, gradient boosting methods, neural networks, and deep learning frameworks. Most models incorporated clinical and pathologic variables, while many integrated radiologic, immunologic, or genomic features. For overall survival prediction, independently validated models generally demonstrated AUCs between 0.80 and 0.90. Recurrence prediction models similarly showed favorable discrimination, with most externally validated studies reporting acceptable predictive performance. Additional prognostic endpoints including disease-free survival, progression, and nodal metastasis demonstrated AUCs ranging from 0.70 to 0.90. Common methodological limitations included retrospective design, small sample size, inadequate external validation, and risk of overfitting. Conclusions: ML-based prognostic models in OCSCC demonstrate generally favorable predictive performance across survival and recurrence outcomes. However, substantial heterogeneity in methodology and limited external validation continue to restrict clinical implementation. Future work should prioritize prospective multicenter validation, standardized reporting, and reproducible modeling frameworks. Full article

Background/Objectives: Frontal sinus surgery remains one of the most challenging procedures in endoscopic sinus surgery due to the complex and variable anatomy of the frontal recess. While several radiological parameters have been proposed to guide surgical planning, there is no standardized anatomical classification that informs both approachability and techniques. This study aimed to develop a reproducible CT-based classification of the nasofrontal beak (NFB) and frontal ostium clearance (FOC), and to validate its surgical applicability through a two-phase design. Methods: A combined retrospective–prospective cohort study was conducted. In Phase 1, CT scans from 1383 patients (2595 sinuses) were analyzed to measure NFB and FOC lengths via a novel technique. The cutoff points were defined through histograms, kernel density estimation, and K-means clustering. In Phase 2, 100 patients (191 sinuses) who underwent frontal sinus surgery were prospectively assessed. Radiological classifications were compared with intraoperative findings, and instruments were selected on the basis of anatomical classes. Agreement between radiological and surgical classifications was analyzed, and surgical outcomes were recorded. Results: NFB and FOC were each classified into three groups: Class A (≤6 mm), Class B (6–12 mm), and Class C (≥12 mm) for NFB, and Class A (≥12 mm), Class B (6–12 mm), and Class C (≤6 mm) for FOC. There was excellent agreement between radiological and intraoperative NFB classes. Class-specific techniques included no modifications for Class A NFB, frontal sinus punches for Class B, and straight/curved drill for Class C. Only one intraoperative lamina papyracea injury and two cases of postoperative neo-ostium narrowing were reported. Significant sex-based anatomical differences and minor side-to-side asymmetries were also observed. Conclusions: This novel classification provides a reproducible, internally validated system for stratifying frontal sinus anatomy preoperatively, with good radiological–surgical concordance for the nasofrontal beak. By mapping the anatomical class onto instrument selection, it offers a practical planning adjunct. As a single-center derivation without an external cohort or comparator arm, it demonstrates anatomical–surgical concordance and feasibility rather than clinical superiority, and warrants multicenter external validation. Full article

Hydrogen peroxide vaporization (HPV) is an established no-touch environmental disinfection technology; however, conventional systems require manual setup and may involve prolonged operating times. This study evaluated a newly developed HPV Smart Robot designed to automate hydrogen peroxide vapor distribution and aeration in a controlled clinical simulation environment. A comparative performance evaluation was conducted in a 48.7 m² clinical simulation enclosure. Four experimental cycles were performed, including one conventional HPV cycle and three robotic HPV cycles operated under different navigation modes and fan-angle configurations. Geobacillus stearothermophilus biological indicators (BIs) were used to assess sporicidal efficacy, while chemical indicators and hydrogen peroxide concentration measurements were used to evaluate vapor distribution. Complete biodecontamination was achieved at all 20 environmental sampling locations in every experiment. When four robot-internal sampling sites were included, biodecontamination rates ranged from 95% to 100%, with a single persistent positive biological indicator detected at a recessed fan–corner junction within the robotic platform. All experiments achieved hydrogen peroxide concentrations above the manufacturer-recommended target threshold (≥140 ppm). Although the robotic system demonstrated greater spatial variability in hydrogen peroxide concentration than the conventional system, effective sporicidal activity was maintained throughout the enclosure. The robotic platform reduced setup time from approximately 15 min to 5 min and shortened total cycle duration from approximately 285 min to 221–231 min. In this controlled simulation study, the HPV Smart Robot demonstrated high microbiological efficacy and improved operational efficiency compared with a conventional HPV workflow. These findings support the feasibility of robotic HPV biodecontamination systems while highlighting the importance of airflow optimization and internal component design to ensure consistent vapor penetration. Full article

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is associated with profound metabolic reprogramming. This exploratory study aimed to characterize the metabolomic profiles of plasma and cerebrospinal fluid (CSF) in children with newly diagnosed pre-B-cell acute lymphoblastic leukemia (pre-B ALL) prior to therapy. Metabolomic analyses were performed using mass spectrometry-based platforms combined with multivariate statistical approaches (PCA, OPLS-DA, SVM-RFE, EBAM). In plasma, we identified 41 significantly altered metabolites (FDR < 0.011), revealing a distinct signature that differentiated pre-B ALL patients from healthy controls. Specifically, patients exhibited elevated levels of hypoxanthine, xanthine, and phosphatidylcholine derivatives, alongside reduced concentrations of L-cysteine and prasterone sulfate, indicating systemic dysregulation of purine, lipid, and amino acid metabolism. In CSF, we observed a distinct metabolic profile characterized by coordinated disturbances in purine degradation, phospholipid metabolism, and sphingolipid pathways. Notably, correlation analysis between the two matrices suggested that systemic metabolic shifts, particularly in purine metabolism (e.g., hypoxanthine and xanthine levels), are mirrored within the central nervous system microenvironment. These findings indicate that children with pre-B ALL exhibit specific metabolic alterations in both compartments before treatment. This work serves as a proof-of-concept for applying metabolomics in pediatric oncology, highlighting the necessity for further validation in larger, prospective cohorts to assess the clinical utility of these profiles. Full article

Background/Objectives: Cutaneous squamous cell carcinomas (cSCC) of the head and neck district are among the most common non melanocytic malignant skin carcinomas. The proposal to differentiate, within the N stage, parotid metastases from lateral cervical metastases, originates from the different prognostic value of the metastatic region involved. Methods: We retrospectively evaluated 61 patients, surgically treated for parotid metastases from cSCC between January 2002 and June 2023, in four Departments of Surgery, to assess the geographic distribution of parotid metastases and to describe their recurrence patterns, to evaluate the prognostic value of the number of affected lateral cervical lymph nodes (LN) and the number of positive intra-glandular lymph nodes (IGLN) and to identify the main prognostic histopathological factors. Results: Our results did not show significant differences between participating centers in the distribution of parotid metastases, nor in their recurrence rates. However, our results highlight how adjuvant radiotherapy is deeply associated with the Overall Survival (OS), improving survival rates in patients with advanced-stage neoplasms (Odds Ratio 5.0), although causality cannot be inferred because of the retrospective study design. Moreover, a statistically significant correlation was found between the major inflammatory biomarkers and the OS. The presence of IGLN was identified as one of the main factors associated with recurrence and poor prognosis in patients with cSCC and in particular, in patients with N3b nodal stage. Conclusions: our findings suggest that both LN and IGLN could be used to propose an additional staging stratification for the N parameter, thereby guiding the treatment strategy and postoperative follow-up for patients with parotid metastases from cSCC of the head and neck district. Full article

Background: Chronic rhinosinusitis with nasal polyps, CRSwNP, represents one of the most clinically relevant models of type 2 inflammation in the upper airways. Its pathogenesis is not sustained by a single mechanism but by the continuous interaction between epithelial barrier damage, immune activation and tissue remodeling. Although several systemic biomarkers are currently used in clinical practice, they do not always reflect the inflammatory processes occurring directly within the sinonasal mucosa. Objective: This review discusses nasal cytology as a local and clinically accessible read-out of type 2 inflammation and epithelial barrier dysfunction in CRSwNP. Particular attention is given to the relationship between cytological patterns, underlying immune mechanisms and the use of biologic therapies. Methods: A narrative review of the literature was conducted, focusing on epithelial barrier abnormalities, type 2 inflammatory pathways, cytological phenotypes and available monoclonal antibodies. The clinical relevance of these elements was considered, with particular regard to patient stratification and therapeutic decision-making. Results: Epithelial barrier disruption promotes the release of alarmins such as TSLP, IL-25 and IL-33. These mediators activate both innate and adaptive type 2 immune responses and contribute to the persistence of mucosal inflammation. Nasal cytology allows direct assessment of the local inflammatory infiltrate and makes it possible to identify eosinophilic, mast cell-predominant and mixed eosinophil–mast cell patterns. These profiles appear to mirror different inflammatory settings. In particular, the coexistence of eosinophils and mast cells may identify patients with more severe, persistent or recurrent disease. When integrated into clinical tools such as clinical–cytological grading (CCG), nasal cytology may improve disease stratification, support follow-up and help orient biologic therapy according to the level of the inflammatory cascade predominantly involved. These cytological profiles may also support biologic treatment selection, therapeutic monitoring, and future tapering strategies by reflecting the predominant inflammatory pathway active at the mucosal level. Conclusions: Nasal cytology is a direct, reproducible and clinically useful approach for evaluating local inflammation in CRSwNP. By providing information from the mucosal site of disease, it complements systemic biomarkers and may support personalized therapeutic strategies and biologic treatment selection in CRSwNP. Full article

Background/Objectives: Cadherin-17 (CDH17, LI-cadherin) is a non-classical cadherin with an atypical structure and unique functions. CDH17 expression is restricted to normal intestinal epithelium. Furthermore, CDH17 functions as an oncoprotein that promotes tumor migration and invasion in colorectal, gastric, and pancreatic cancers. Therefore, CDH17 is an important diagnostic marker and therapeutic target. The CDH17-directed strategies, including monoclonal antibodies (mAbs), bispecific Abs, antibody–drug conjugates (ADCs), and chimeric antigen receptor (CAR) T cells, have been evaluated in preclinical and clinical studies. Therefore, developing mAbs that specifically recognize cell surface-expressing CDH17 is essential for advancing both tumor diagnosis and therapy. Methods: Anti-human CDH17 mAbs (named Ca₁₇Mabs) were developed by immunizing a mouse with CDH17-overexpressed cells and a high-throughput screening using flow cytometry. Results: Among Ca₁₇Mabs, a clone, Ca₁₇Mab-5 (IgG₁, κ) specifically recognized CDH17-overexpressed Chinese hamster ovary-K1 (CHO/CDH17) cells with no detectable cross-reactivity to 21 other CDHs by flow cytometry. Ca₁₇Mab-5 also detected endogenous CDH17 in human colorectal cancer cell lines, COLO201 and COLO205. The apparent dissociation constant (K_D) values of Ca₁₇Mab-5 for CHO/CDH17 and COLO205 were estimated as 1.5 × 10⁻⁸ M and 1.3 × 10⁻⁸ M, respectively. Furthermore, Ca₁₇Mab-5 detected endogenous CDH17 by Western blotting. In immunohistochemistry, Ca₁₇Mab-5 exhibited clear membranous staining in normal colon epithelium, colorectal, gastric, and pancreatic cancers. Conclusions: Ca₁₇Mab-5 is a versatile tool for detecting CDH17 and has potential for tumor diagnosis. Full article

Background/Objectives: Allergic rhinitis (AR) is a highly prevalent chronic inflammatory disease of the upper airway characterized by immune dysregulation. This study aimed to systematically characterize the immunomodulatory landscape of AR and identify exploratory molecular and cellular features associated with disease-related immune remodeling. Methods: Public bulk transcriptomic datasets and single-cell RNA sequencing data were integrated to identify immunomodulatory-related differentially expressed genes (IMRDEGs), construct an immunomodulatory score (IM.Score), evaluate immune cell infiltration, and characterize cell-type composition and intercellular communication. Machine learning was used to derive an exploratory molecular signature, and L1000CDS2-based drug repositioning analysis was performed to identify in silico candidate compounds predicted to oppose AR-associated transcriptional signatures. Results: A total of 12 IMRDEGs were identified and used to construct the IM.Score, which was lower in AR samples relative to control samples. Immune infiltration analysis demonstrated that IM.Score stratification was associated with distinct immune microenvironmental profiles. Single-cell analysis revealed potential reductions in CD4⁺ central memory T cells, which represent an immune cellular alteration requiring further experimental verification, alongside attenuated intercellular communication involving this cell population. A six-gene exploratory molecular signature comprising NFKBIA, PDCD1, MYC, IFNG, FOXP3, and CD274 showed favorable performance in the training cohort (AUC = 0.992, 95% CI: 0.974–1.000) but failed to generalize in the external validation cohort (AUC = 0.500, 95% CI: 0.245–0.755), precluding clinical diagnostic interpretation at this stage. Drug repositioning analysis identified candidate compounds, including narciclasine and BRD-K91370081, with the potential to reverse AR-associated transcriptional alterations. Conclusions: This integrative multi-omics analysis identifies coordinated molecular, cellular, and communication-level immune alterations in AR. The IM.Score, altered CD4⁺ central memory T-cell abundance, and six-gene exploratory molecular signature may be regarded as hypothesis-generating candidate clues pending further experimental and clinical validation. Full article

Background: Olfactory dysfunction (OD) is prevalent in people with cystic fibrosis (PwCF); however, its overall impact in this population is understudied. No systematic review on this topic is currently available. Objective: The objective of this study was to systematically review the existing literature on OD in PwCF. Methods: A systematic review was performed using PRISMA guidelines. Inclusion criteria consisted of articles that examined OD in PwCF using psychophysical olfactory testing. PubMed, Ovid Medline, Google Scholar, Cochrane Library, MedRxiv, and Web of Science databases were searched on 13 June 2022. The Newcastle–Ottawa Scale was used to assess the quality and determine risk of bias for the studies included in the meta-analysis. Results: A total of 87 articles were initially identified; ten were ultimately included. All ten studies were prospective and observational. A total of 420 PwCF were included in these studies (209 females, mean age = 26 years). Psychophysical olfactory testing was performed via the 40-Question Smell Identification Test (n = 4 studies), Sniffin’ Sticks Testing (n = 4 studies), and other odor identification tests (n = 2 studies). The mean prevalence of OD was 61% (range 10–88%), while rates of anosmia ranged from 5 to 14. The meta-analysis demonstrated that PwCF had lower threshold, discrimination, and identification scores compared to controls, with a very large effect size (Hedges’ g = −1.57, 95% CI = −2.51 to −0.63). Five studies revealed impairment in odor identification. Five studies assessed potential associations between OD and body mass index. Conclusions: OD is common in PwCF. Most PwCF have hyposmia, while anosmia is less common. Olfactory limitations have not been well characterized in pediatric patients. Understanding how OD affects PwCF is critical to optimization of disease management and quality of life. Full article