Dupilumab Therapy Modulates Circulating Inflammatory Mediators in Patients with Prurigo Nodularis.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus and skin nodules. Beyond the skin, PN involves circulating blood inflammation that may contribute to systemic disease comorbidities. Dupilumab was recently approved for treatment of PN, but its effects on systemic inflammation are unknown. Thus, we aimed to characterize changes in plasma concentrations of inflammatory proteins after dupilumab treatment. In this exploratory study, plasma samples were collected from 3 patients with moderate-to-severe PN before and after ≥6 months of dupilumab treatment. All patients exhibited clinically significant improvements after treatment. Of the 2569 proteins tested, 186 were differentially expressed after treatment (q < 0.1, fold change > 1.3). Downregulated proteins included cytokines associated with T helper (Th) 1 (IFN-γ, TNF-α), Th2 (IL-4, IL-13), and Th17/Th22 (IL-6, IL-22) signaling. Markers of innate immunity (IL-19, toll-like receptor 1, nitric oxide synthase 2), immune cell migration (CCL20, CD177), and fibrosis (IL-11, IL-22) were also decreased (q < 0.1). Gene set variation analysis of Th2, Th17, and epithelial-mesenchymal transition gene sets showed reduced pathway expression in the post-treatment cohort (P < .05). Plasma cytokine levels of IL-11, nitric oxide synthase 2, IL-13, IL-4, and IFNG (R2 > 0.75, q < 0.10) showed the strongest correlations with pruritus severity. Dupilumab may reduce systemic inflammatory proteins associated with multiple immune and fibrosis pathways in patients with PN, potentially modulating the development of systemic disease comorbidities.

Plasma metabolomic profiling reveals a novel circulating biomarker signature in chronic pruritus of unknown origin.

Chronic pruritus of unknown origin (CPUO) is characterized by chronic itch for 6 weeks or greater without an identifiable primary cause. Studies are needed to investigate circulating blood biomarkers to elucidate disease pathogenesis. The objective of this study was to investigate changes in circulating blood metabolites in CPUO patients and to identify potential therapeutic targets. Our cross-sectional study collected plasma from 11 CPUO patients and 11 matched control patients for mass-spectrometry based metabolite data analysis. 15 metabolites differed significantly in the blood of CPUO patients compared to controls, including nine amino acids (isoleucine, L-tyrosine, threonine, DL-tryptophan, L-valine, methionine, glycine, lysine, and L-phenylalanine), four amino acid derivatives (creatinine, DL-carnitine, acetyl-L-carnitine, and indole-3-acrylic acid), and two aromatic and fatty acid derivatives (2-hydroxycinnamic acid and oleamide). These metabolites were also correlated with itch severity. Metabolic set enrichment analysis (MSEA) identified downregulation of several pathways in CPUO: phenylalanine, tyrosine, tryptophan biosynthesis; catecholamine biosynthesis; and glycine, serine, and threonine metabolism. Our study identified decreases in several circulating plasma metabolites in CPUO patients and downregulation of pathways related to catecholamine biosynthesis and tryptophan biosynthesis, providing insight into the pathogenesis of CPUO.

What proportion of CT scan patients are alive or deceased after 10 years?

PURPOSE: When discussing radiation risks for patients who undergo many CT examinations, some question the risks, believing that most of these patients are already very sick and likely to die within a few years, thus negating worry about radiation risk. This study seeks to evaluate the validity of this notion. METHODS: In this retrospective single large-hospital study, patients who received CT exams in 2013 were sorted into four cumulative effective dose (CED) groups: Group A (>0 to <10 mSv), Group B (10 to <50 mSv), Group C (50 to < 100 mSv), and Group D (≥100 mSv). The death rates of patients in each group were analyzed, up to December 2023. RESULTS: 36,545 patients underwent CT examinations in 2013 (mean age, 56 ± 20 years, 51.4 % men). Death rates for all dose groups peaked in the year of imaging or 1 year after. At one year after imaging, Group D had 6.7 times and Group C had 4.3 times the death rate of Group A. However, a significant portion of these patients are alive after 10 years, with 1324/2756 patients (48.0 %) in Group C and 282/769 patients (36.7 %) in Group D with the potential to face radiation effects. CONCLUSIONS: While it is true that patients receiving relatively higher doses (≥50 mSv) are more likely to die within the first two years of receiving such doses, nearly one-third to half remain alive a decade after their CT scans, potentially facing the effects of radiation. This knowledge may help policymakers and practitioners.

Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin: A Nonrandomized Controlled Trial.

Importance: Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions. Objective: To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO. Design, Setting, and Participants: This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period. Intervention: Abrocitinib, 200 mg, by mouth once daily for 12 weeks. Main Outcomes and Measures: The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores. Results: A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, -118.5 to -38.1; P < .001) and 53.7% in CPUO (95% CI, -98.8 to -8.6; P = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: -53.2% [95% CI, -75.3% to -31.1%]; P = .002; CPUO: -49.0% [95% CI, -89.6% to -8.0%]; P = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred. Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT05038982.

Immune stimulus exposure as a trigger for the development of chronic pruritus and circulating blood type 2 inflammation.

Background: Chronic pruritus (CP) is a poorly characterized condition associated with intense pruritus without a primary skin eruption. This condition tends to emerge more commonly in older adults, and there is limited research on triggering factors. Objective: To explore the clinical characteristics and pathophysiology of CP following exposure to an immune stimulus. Methods: Clinical characteristics and plasma samples were collected from 15 patients who developed CP following an immune stimulus such as checkpoint inhibitors or vaccination. A multiplex panel was used to analyze plasma cytokine concentrations within these patients. Results: Most immunotherapy-treated patients experienced CP during treatment or after 21 to 60 days of receiving treatment, while vaccine-stimulated patients developed pruritus within a week of vaccination. Plasma cytokine analysis revealed elevated levels of 12 cytokines in patients with immune-stimulated CP compared to healthy controls. Notably, T helper 2 (Th2) related cytokines interleukin (IL)-5 (fold change 2.65; q < 0.25) and thymic stromal lymphopoietin (fold change 1.61 q < 0.25) were upregulated. Limitations: Limitations of this study include limited sample size, particularly in the plasma cytokine assay. Conclusions and Relevance: This study reveals triggers of CP development and describes alterations in blood Th2 markers in patients with CP, including IgE, increased blood eosinophils, and cytokines IL-5 and thymic stromal lymphopoietin.

Environmental, economic, and social sustainability in aquaculture: the aquaculture performance indicators.

Aquaculture is a rapidly growing food production technology, but there are significant concerns related to its environmental impact and adverse social effects. We examine aquaculture outcomes in a three pillars of sustainability framework by analyzing data collected using the Aquaculture Performance Indicators. Using this approach, comparable data has been collected for 57 aquaculture systems worldwide on 88 metrics that measure social, economic, or environmental outcomes. We first examine the relationships among the three pillars of sustainability and then analyze performance in the three pillars by technology and species. The results show that economic, social, and environmental outcomes are, on average, mutually reinforced in global aquaculture systems. However, the analysis also shows significant variation in the degree of sustainability in different aquaculture systems, and weak performance of some production systems in some dimensions provides opportunity for innovative policy measures and investment to further align sustainability objectives.

Dose, dose, dose, but where is the patient dose?

The article reviews the historical developments in radiation dose metrices in medical imaging. It identifies the good, the bad, and the ugly aspects of current-day metrices. The actions on shifting focus from International Commission on Radiological Protection (ICRP) Reference-Man-based population-average phantoms to patient-specific computational phantoms have been proposed and discussed. Technological developments in recent years involving AI-based automatic organ segmentation and 'near real-time' Monte Carlo dose calculations suggest the feasibility and advantage of obtaining patient-specific organ doses. It appears that the time for ICRP and other international organizations to embrace 'patient-specific' dose quantity representing risk may have finally come. While the existing dose metrices meet specific demands, emphasis needs to be also placed on making radiation units understandable to the medical community.

Spondylodiscitis: A Diagnostic and Management Dilemma.

Aims Spondylodiscitis (SpD), a debilitating infective condition of the spine, mandates early diagnosis and institution of appropriate therapy, for which accurate microbiology and histological evaluation of the affected tissue is vital. The objectives of the study were to assess the correlation between clinical and magnetic resonance imaging (MRI) findings with histopathology (HPE) and microbiology (MB) in clinically diagnosed spondylodiscitis. Settings and design This was a prospective study of 34 consecutive patients reporting at the outpatient department of a tertiary hospital with clinical and imaging features of SpD, who underwent image-guided/surgical biopsy of lesions. Methods and material The provisional diagnosis of SpD in all patients was made on the combined basis of clinical profile and MRI Spine findings. Tissue samples in all patients, obtained by either open surgery or CT-guided biopsy, were subjected to HPE and MB analysis.  Results SpD has a bimodal age distribution with the majority of patients being males in the fourth to fifth decades. Only raised erythrocyte sedimentation rate (ESR) was consistently seen amongst laboratory parameters, with leucocytosis being added pointer towards pyogenic etiology. MRI remained the imaging modality of choice for SpD but was not dependable for etiologic differentiation. On HPE and MB evaluations, 24 patients (71%) had findings consistent with infective SpD, while combined results augmented etiologic confirmation for 28 patients (82.4%). HPE was more sensitive than traditional MB methods to determine etiology in SpD, but the addition of the GeneXpert (Cepheid, Sunnyvale, California, United States) technique improved the MB positivity rate, especially in patients with tubercular SpD. Six patients (17.6%) with both negative HPE and MB results were categorized as 'Non-specific' SpD. Conclusions SpD poses a challenge to determine the etiology for the administration of specific antimicrobial therapy. A stratified standard institutional approach needs adoption to systematically evaluate SpD patients by having a high index of clinical suspicion, early imaging, followed by tissue biopsy for HPE and MB. Despite efforts to reach a diagnosis, a subset of patients without conclusive etiologic agent identification would remain as 'Non-specific', needing empiric antibiotic treatment based on clinico-radiologic profile.

Prevalence and Risk Associated With Bladder Injuries During Caesarean Section in a Secondary Care Hospital.

Introduction Bladder injury during caesarean section (CS) is not uncommon. Various factors increase the risk of bladder injury during CS, including prolonged labor with bladder distension, pregnancy with a scarred uterus, suspected intra-abdominal adhesions, distorted local anatomy, cesarean hysterectomy, and an increasing number of previous CS. Vigilant preoperative assessment and surgical precision are essential to mitigate these risks and ensure optimal outcomes for mother and child. Objectives To find out the prevalence and risk factors associated with bladder injuries during caesarean section. Methodology Hospital-based retrospective record review of 3600 pregnant women who had undergone cesarean section during the period January 2015 to December 2023 were included in the study. Data was analyzed using SPSS software, version 22 (trial version) (IBM Corp., Armonk, NY). The Chi-square test and Fisher's exact test were used. Ethical clearance was obtained from the Institutional Ethics Committee at Tata Main Hospital Noamundi (approval number NI/CMO/26/24). Result Bladder injury prevalence was reported to be 1.1%. Bladder injuries were significantly (p<0.0001) more among the CS cases with underlined complications as compared to CS cases without any underlined complications. Repeat CSs were found to have a significantly (p<0.001) higher proportion of bladder injuries compared to primary CS.  Conclusion Bladder injuries during cesarean section are a significant concern. The risk factors identified, such as the number of previous cesarean sections and complications during pregnancy, highlight the importance of careful preoperative assessment and surgical precision to prevent such injuries.

Comprehensive plasma cytokine and chemokine profiling in prurigo nodularis reveals endotypes in Type 2 inflammation.

Prurigo nodularis (PN) is a chronic inflammatory skin disease that is associated with variability in peripheral blood eosinophil levels and response to T-helper 2 targeted therapies (Th2). Our objective was to determine whether circulating immune profiles with respect to type 2 inflammation differ by race and peripheral blood eosinophil count. Plasma from 56 PN patients and 13 matched healthy controls was assayed for 54 inflammatory biomarkers. We compared biomarker levels between PN and HCs, among PN patients based on absolute eosinophil count, and across racial groups in PN. Eleven biomarkers were elevated in PN versus HCs including interleukin (IL)-12/IL-23p40, tumor necrosis factor-alpha (TNF-α), Thymic stromal lymphopoietin (TSLP), and macrophage-derived chemokine (MDC/CCL22). Additionally, PN patients with AEC > 0.3 K cells/µL had higher Th2 markers (eotaxin, eotaxin-3, TSLP, MCP-4/CCL13), and African American PN patients had lower eosinophils, eotaxin, and eotaxin-3 versus Caucasian and Asian PN patients (p < 0.05 for all). Dupilumab responders had higher AEC (p < 0.01), were more likely to be Caucasian (p = 0.02) or Asian (p = 0.05) compared to African Americans, and more often had a history of atopy (p = 0.08). This study suggests that blood AEC > 0.3 K and Asian and Caucasian races are associated with Th2 skewed circulating immune profiles and response to Th2 targeted therapies.

Integrated plasma metabolomic and cytokine analysis reveals a distinct immunometabolic signature in atopic dermatitis.

Importance: Disease models for atopic dermatitis (AD) have primarily focused on understanding underlying environmental, immunologic, and genetic etiologies. However, the role of metabolic mechanisms in AD remains understudied. Objective: To investigate the circulating blood metabolomic and cytokine profile of AD as compared to healthy control patients. Design: This study collected plasma from 20 atopic dermatitis with moderate-to-severe itch (score of ≥5 on the itch Numeric Rating Scale and IGA score ≥3) and 24 healthy control patients. Mass-spectrometry based metabolite data were compared between AD and healthy controls. Unsupervised and supervised machine learning algorithms and univariate analysis analyzed metabolic concentrations. Metabolite enrichment and pathway analyses were performed on metabolites with significant fold change between AD and healthy control patients. To investigate the correlation between metabolites levels and cytokines, Spearman's rank correlation coefficients were calculated between metabolites and cytokines. Setting: Patients were recruited from the Johns Hopkins Itch Center and dermatology outpatient clinics in the Johns Hopkins Outpatient Center. Participants: The study included 20 atopic dermatitis patients and 24 healthy control patients. Main outcomes and measures: Fold changes of metabolites in AD vs healthy control plasma. Results: In patients with AD, amino acids isoleucine, tyrosine, threonine, tryptophan, valine, methionine, and phenylalanine, the amino acid derivatives creatinine, indole-3-acrylic acid, acetyl-L-carnitine, L-carnitine, 2-hydroxycinnamic acid, N-acetylaspartic acid, and the fatty amide oleamide had greater than 2-fold decrease (all P-values<0.0001) compared to healthy controls. Enriched metabolites were involved in branched-chain amino acid (valine, leucine, and isoleucine) degradation, catecholamine biosynthesis, thyroid hormone synthesis, threonine metabolism, and branched and long-chain fatty acid metabolism. Dysregulated metabolites in AD were positively correlated cytokines TARC and MCP-4 and negatively correlated with IL-1a and CCL20. Conclusions and relevance: Our study characterized novel dysregulated circulating plasma metabolites and metabolic pathways that may be involved in the pathogenesis of AD. These metabolic pathways serve as potential future biomarkers and therapeutic targets in the treatment of AD.

Spatial Mass Cytometry-Based Single-Cell Imaging Reveals a Disrupted Epithelial-Immune Axis in Prurigo Nodularis.

Prurigo nodularis (PN) is a chronic, inflammatory skin condition that disproportionately affects African Americans and features intensely pruritic, hyperkeratotic nodules on the extremities and trunk. PN is understudied compared with other inflammatory skin diseases, with the spatial organization of the cutaneous infiltrate in PN yet to be characterized. In this work, we employ spatial imaging mass cytometry to visualize PN lesional skin inflammation and architecture with single-cell resolution through an unbiased machine learning approach. PN lesional skin has increased expression of caspase 3, NF-kB, and phosphorylated signal transducer and activator of transcription 3 compared with healthy skin. Keratinocytes in lesional skin are subdivided into CD14+CD33+, CD11c+, CD63+, and caspase 3-positive innate subpopulations. CD14+ macrophage populations expressing phosphorylated extracellular signal-regulated kinase 1/2 correlate positively with patient-reported itch (P = .006). Hierarchical clustering reveals a cluster of patients with PN with greater atopy, increased NF-kB+ signal transducer and activator of transcription 3-positive phosphorylated extracellular signal-regulated kinase 1/2-positive monocyte-derived myeloid dendritic cells, and increased vimentin expression (P < .05). Neighborhood analysis finds interactions between CD14+ macrophages, CD3+ T cells, monocyte-derived myeloid dendritic cells, and keratinocytes expressing innate immune markers. These findings highlight phosphorylated extracellular signal-regulated kinase-positive CD14+ macrophages as contributors to itch and suggest an epithelial-immune axis in PN pathogenesis.

Impact of equipment technology on reference levels in fluoroscopy-guided gastrointestinal procedures.

OBJECTIVES: To evaluate the effect of equipment technology on reference point air kerma (Ka,r), air kerma-area product (PKA), and fluoroscopic time for fluoroscopically-guided gastrointestinal endoscopic procedures and establish benchmark levels. METHODS: This retrospective study included the consecutive patients who underwent fluoroscopically-guided gastrointestinal endoscopic procedures from May 2016 to August 2023 at a tertiary care hospital in the U.S. Fluoroscopic systems included (a) Omega CS-50 e-View, (b) GE Precision 500D, and (c) Siemens Cios Alpha. Radiation dose was analyzed for four procedure types of endoscopic retrograde biliary, pancreas, biliary and pancreas combined, and other guidance. Median and 75th percentile values were computed using software package R (version 4.0.5, R Foundation). RESULTS: This large study analyzed 9,459 gastrointestinal endoscopic procedures. Among four procedure types, median Ka,r was 108.8-433.2 mGy (a), 70-272 mGy (b), and 22-55.1 mGy (c). Median PKA was 20.9-49.5 Gy∙cm2 (a), 13.4-39.7 Gy∙cm2 (b), and 8.91-20.9 Gy∙cm2 (c). Median fluoroscopic time was 2.8-8.1 min (a), 3.6-9.2 min (b), and 2.9-9.4 min (c). Their median value ratio (a:b:c) was 8.5:4.8:1 (Ka,r), 2.7:2.1:1 (PKA), and 1.0:1.1:1 (fluoroscopic time). Median value and 75th percentile are presented for Ka,r, PKA, and fluoroscopic time for each procedure type, which can function as benchmark for comparison for dose optimization studies. CONCLUSION: This study shows manifold variation in doses (Ka,r and PKA) among three fluoroscopic equipment types and provides local reference levels (50th and 75th percentiles) for four gastrointestinal endoscopic procedure types. Besides procedure type, imaging technology should be considered for establishing diagnostic reference level. SUMMARY: With manifold (2 to 12 times) variation in doses observed in this study among 3 machines, we recommend development of technology-based diagnostic reference levels for gastrointestinal endoscopic procedures.

How healthy is the health budget of Amrit Kaal: 2023-24?

Political will is the key to public health policy-making and a major driving force for the attainment of Universal Health Coverage (UHC) in any nation. To achieve UHC, the Indian government laid down National Health Policy in 1983 and updated it in 2002 and recently in 2017. This recent policy emphasized increasing healthcare spending and economic growth. In the current budget, there is an increment in the share of GDP of 0.34% from the previous year's allocation, but still staggering for the envisaged 2.5% to achieve UHC. Enthusiastic announcements of opening 157 new nursing colleges, a separate programme for eliminating sickle cell anemia by 2047, and Centers of excellence establishment for pharma companies for promoting research and development and focusing on Particularly Vulnerable Tribal Groups (PVTGs) are the few overarching and new highlights in the current budget. But, in a country so huge and varied in terms of its needs in every sector, the announcements in the financial budget speech taking India forward in becoming a "shining star" is a matter of debate. This is an attempt to review the budget for this financial year in the healthcare sector and what it means: is the country willing to build a self-driven healthcare sector in the Amrit Kaal with strong public finances and a robust financial sector through "efforts by all"?

Characterizing imaging radiation risk in a population of 8918 patients with recurrent imaging for a better effective dose.

An updated extension of effective dose was recently introduced, namely relative effective dose ( E r ), incorporating age and sex factors. In this study we extended E r application to a population of about 9000 patients who underwent multiple CT imaging exams, and we compared it with other commonly used radiation protection metrics in terms of their correlation with radiation risk. Using Monte Carlo methods, E r , dose-length-product based effective dose ( E DLP ), organ-dose based effective dose ( E OD ), and organ-dose based risk index ( RI ) were calculated for each patient. Each metric's dependency to RI was assessed in terms of its sensitivity and specificity. E r showed the best sensitivity, specificity, and agreement with RI (R2 = 0.97); while E DLP yielded the lowest specificity and, along with E OD , the lowest sensitivity. Compared to other metrics, E r provided a closer representation of patient and group risk also incorporating age and sex factors within the established framework of effective dose.

Is a one percent occurrence of high-dose patients significant?

Risk-free society is utopian. We come across risks in everyday life, and we use probabilities to get a feel of how risky a situation is. Risk probability numbers of around 1% are comforting, but an intercomparison of numbers among various low risks in popular situations can be enlightening. In this article, we compare risks of complications or death in several surgeries and risks in commercial air travel with risks for patients getting cumulative effective dose (CED) of 100 mSv or more, as the latter is a hot and controversial topic currently. The analysis shows that many common surgeries are a few tens or hundreds of times less risky than the risk from a 100 mSv dose, even though the former often frightens us more. Despite there being a much higher chance of developing cancer from radiation than being involved in a commercial plane accident, there is much less emphasis on patient radiation safety than aviation safety. Further, a look at the system of control on prescription drugs indicates that there is much to learn for policy planning. This analysis may help the International Commission on Radiological Protection (ICRP) in their review of recommendations.

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis.

Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB-like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB-associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand-receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB-associated malignancies in patients with PN.