Search Results (107)

Background: Persistent low-grade inflammation has been proposed as part of the biological mechanisms underlying post-COVID condition (PCC), which can result in laboratory tests abnormalities. However, the accuracy of routine laboratory tests for the diagnosis and follow-up of PCC is still under discussion. Methods: Patients with SARS-CoV-2 infection enrolled in the prospective, multinational ORCHESTRA cohort study, which included both European and non-European countries, were followed up for 18 months after acute infection. Blood test results were collected at acute infection and at 6, 12, and 18 months. A multivariable analysis was performed to estimate the relationship between the alterations of biochemical markers and the presence of four distinct PCC phenotypes, identified previously through a principal component analysis—respiratory (RESc), chronic pain (CPc), chronic fatigue (CFc), and neurosensorial (NSc)—during follow-up. Furthermore, this study investigated the correlation between biochemical parameters measured during the acute phase and the subsequent development of PCC. Finally, the relationship between the severity of the acute infection and biochemical abnormalities observed during follow-up was assessed. Results: The cohort included 4587 patients, 58% male, with a mean age of 58.7 (±15.5) years. A robust multivariable analysis demonstrated that, compared to controls, patients with PCC, and in particular those in the RESc cluster, presented higher mean C-reactive protein (CRP) levels at the 12- and 18-month follow-up (p-value = 0.01). In each follow-up, CRP values in patients with PCC and RESc were above 3 mg/L, corresponding to those observed in low-grade inflammation (3–10 mg/L). The severity of COVID-19 acute infection was associated with increased levels of CRP, ferritin and LDH during follow-up (p < 0.001). Biochemistry abnormalities detected during the early stages of acute COVID-19 did not correlate with an increased risk of developing PCC and its phenotypes. Conclusions: In patients with the RESc PCC phenotype, identified through a principal component analysis, blood test abnormalities consistent with prolonged and sustained low-grade inflammation can be detected up to 18 months after acute infection, supporting its role in the pathogenesis of PCC. Based on these results, trials on anti-inflammatory drugs, together with symptom-tailored interventions for patients with RESc, should be planned to prove their effectiveness in managing PCC and improving patient outcomes. Full article

Cigarette smoking is the leading preventable cause of chronic diseases (e.g., COPD, cardiovascular disease, cancer), largely driven by persistent immune-inflammatory mechanisms. This review synthesizes the molecular and cellular cascades linking cigarette smoke (CS) exposure to chronic pathology. CS constituents, particularly ROS/RNS, induce rapid oxidative stress that overwhelms antioxidant defenses and generates damage-associated molecular patterns (DAMPs). These DAMPs activate pattern recognition receptors (PRRs) and the NLRP3 inflammasome, initiating NF-κB signaling and the release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). CS exposure causes profound innate immune dysregulation, including airway epithelial barrier disruption, hyperactivated neutrophils, and dysfunctional alveolar macrophages (AMs) that release destructive proteases (e.g., MMP-12) and acquire foam-cell–like characteristics. Furthermore, CS drives adaptive immunity toward a Th1/Th17-dominant phenotype while suppressing regulatory T-cell (Treg) function, thereby promoting autoimmunity and chronic tissue injury. Critically, CS induces epigenetic reprogramming (e.g., DNA methylation, miRNA dysregulation), locking immune cells into a persistent pro-inflammatory state. This convergence of oxidative stress, innate and adaptive immune dysregulation, and epigenetic alterations underlies the systemic low-grade inflammation that fuels smoking-related chronic diseases, highlighting key targets for novel therapeutic interventions. Full article

Chronic kidney disease (CKD) is a frequent and clinically significant comorbidity in patients with rheumatoid arthritis (RA), with a reported prevalence ranging from 20% to 50% depending on the cohort and definition applied. The high burden of CKD in RA reflects the complex interplay between traditional risk factors (aging, hypertension, diabetes, and dyslipidemia) and RA-specific factors such as persistent systemic inflammation, immune complex deposition, and long-term exposure to nephrotoxic agents, including older DMARDs (gold, D-penicillamine) and calcineurin inhibitors. Histopathologically, RA-associated kidney involvement encompasses a broad spectrum of conditions, including mesangial proliferative glomerulonephritis, membranous nephropathy, AA amyloidosis, and drug-induced interstitial nephritis. Recent advances in RA therapy, particularly the widespread use of biologic DMARDs, have markedly reduced the incidence of AA amyloidosis and may exert indirect renoprotective effects through stringent inflammation control. However, targeted synthetic DMARDs such as Janus kinase (JAK) inhibitors require careful dose adjustment in CKD and heightened infection vigilance. CKD in RA is a strong predictor of cardiovascular events, serious infections, and all-cause mortality. Importantly, recent data indicate that even low-grade albuminuria below the traditional microalbuminuria threshold is associated with excess mortality in RA. Early detection through routine monitoring of eGFR and urinary albumin-to-creatinine ratio (uACR), combined with individualized pharmacologic adjustment and close collaboration with nephrologists, is essential for optimizing long-term outcomes. This review provides an updated synthesis of the epidemiology, pathophysiological mechanisms, therapeutic strategies, and prognostic implications of CKD in RA, with a particular focus on both Japanese and international evidence. Full article

Introduction: Immune dysfunction plays a significant role in Metabolic syndrome, contributing to both insulin resistance and chronic low-grade inflammation. This immune dysfunction is characterized by overproduction of inflammatory cytokines among which of primary importance are tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and (MCP-1), whereas others such as interferon gamma (IFN-γ), IL-17A, and the anti-inflammatory IL-10 appear to be of secondary importance. Cytokines also play a significant role in Post-COVID disorders contributing to prolonged immune dysregulation and persistent subclinical inflammation. However, their role in the newly emerging metabolic disorders following infection remains poorly defined. Methods and materials: In the current study 78 patients (26 men and 52 women) were included, divided into two groups—group 1 (individuals with newly diagnosed carbohydrate disorders after proven COVID-19 or Post-COVID group; n = 35) and group 2 (COVID-19 negative persons with Metabolic Syndrome; n = 33). They were further divided into several subgroups according to type of metabolic disorder present. Standard biochemical, hormonal and immunological parameters were measured using ELISA and ECLIA methods, as well as some indices for assessment of insulin resistance were calculated using the corresponding formula. Results: Patients from both groups demonstrate similar metabolic parameters including BMI and unadjusted lipid and uric acid levels (p > 0.05). After adjustment for age, sex, and BMI revealed significant differences, Post-COVID status independently predicted higher fasting glucose, HbA1c, total cholesterol, LDL-cholesterol, triglycerides, uric acid, and insulin-resistance indices, indicating substantially impaired glycemic and metabolic control beyond traditional risk factors. Furthermore, the Post-COVID cohort demonstrated marked cytokine dysregulation, with significantly elevated levels of TNF-α, IFN-γ, IL-17A, and IL-10 after adjustment. Conclusions: The observed changes in both metabolic and immune parameters studied among the two groups show many similarities, but some significant differences have also been identified. Together, these findings indicate that Post-COVID metabolic dysfunction is characterized by inflammation-driven dyslipidemia, heightened oxidative stress, and persistent immune activation, distinguishing it from classical Metabolic syndrome. Full article

Residual cardiovascular risk remains a major challenge in coronary artery disease, even after optimal lipid-lowering and anti-inflammatory therapy. Beyond classical risk factors, persistent low-grade inflammation and fibrotic remodeling contribute to adverse outcomes that current treatments fail to fully prevent. Growing evidence highlights the glyco-inflammatory axis—the interplay between protein glycosylation-dependent signaling and inflammation—as an underappreciated contributor to residual atherosclerotic risk, largely because current therapeutic strategies do not directly target glycan-mediated mechanisms. Within this framework, Galectin-3 (Gal-3), a β-galactoside-binding lectin, has emerged as a key molecular hub linking metabolic stress, lysosomal dysfunction, and vascular remodeling. By recognizing specific glycan motifs on immune and stromal cells, Gal-3 orchestrates macrophage activation, endothelial dysfunction, and extracellular matrix deposition, thereby amplifying chronic inflammation and fibrosis. Elevated circulating Gal-3 levels are associated with plaque vulnerability and major adverse cardiovascular events, independent of lipid or C-reactive protein levels. Experimental Gal-3 inhibition reduces inflammation and fibrosis in preclinical models, supporting its therapeutic potential. This review integrates mechanistic, translational, and clinical evidence to propose Gal-3 as a missing link between intracellular stress responses and extracellular fibro-inflammatory remodeling. Targeting the Gal-3-mediated glyco-inflammatory axis may represent a novel strategy to overcome residual cardiovascular risk and achieve comprehensive vascular protection in the post-statin era. Full article

Post-COVID cardiac complications have emerged as a significant and persistent clinical concern, yet their underlying mechanisms remain poorly understood. Animal models can act as proxies to investigate the pathophysiology of the human, post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this experimental study was to evaluate the expression of inflammatory biomarkers in cardiac tissue 28 days after SARS-CoV-2 infection in a female hACE2 mouse model, with a focus on chemokine-mediated immune activation. Twelve female C57BL/6 hACE2 mice were infected with the Omicron variant (BA.1.17 lineage) of SARS-CoV-2, and eleven non-infected mice served as controls. Cardiac tissue was analyzed via Western blot for markers of innate immune activation (TLR4, MyD88, NF-κB) and pro-inflammatory cytokines (IL-6, IL-18, IL-1β, TNF-α, CD11d). Cardiac tissue injury markers (iNOS, PAI-1 and Connexin43) were also analyzed. Compared to non-infected mice, cardiac tissue from infected mice showed significantly higher expression of IL-6 (p = 0.028), indicating an inflammatory state, and CD11d (p = 0.016), suggesting an inflammatory stage accompanied by sustained activation of chemokine-mediated inflammatory signaling. No significant differences in TLR4 (p = 0.340), MyD88 (p = 0.410), NF-κB p65 (p = 0.780), IL-18 (p = 0.548), IL-1β (p = 0.455), and TNF-α (p = 0.125) expressions were observed Similarly, no changes in cardiac damage markers (iNOS: p = 0.4684; PAI-1: p = 0.5345; Connexin 43: p = 0.2879) were found. The results of this experimental study would support the hypothesis of persistent low-grade inflammation as a contributor to post-COVID cardiac sequelae in females that is not accompanied by severe tissue damage, as also observed in clinical studies. This study also reinforces the need for studies evaluating the functional and structural evolution of the myocardium after an acute SARS-CoV-2 infection. Full article

Background: Functional imbalance within the stomatognathic system can develop long before clinical symptoms become evident. Subtle biological changes, such as low-grade inflammation or metabolic disturbance, may precede gingival inflammation, temporomandibular discomfort, or masticatory muscle sensitivity. This study introduces the BioRisk-S (Biological Risk–Stomatognathic System) algorithm, a predictive model designed to identify early systemic alterations associated with the subclinical stage of stomatognathic dysfunction. Methods: A total of 260 clinically healthy adults without apparent stomatognathic disorders were enrolled and evaluated at baseline (T0) and re-examined after six months (T1). Routine laboratory tests were performed to determine high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), and 25-hydroxyvitamin D levels. These biomarkers were integrated into the BioRisk-S algorithm to estimate systemic biological imbalance. Follow-up examinations focused on detecting early functional changes, including gingival inflammation, signs of temporomandibular joint (TMJ) dysfunction, and masticatory muscle tenderness. Results: Participants with higher baseline BioRisk-S scores showed significantly higher hs-CRP and NLR values, as well as lower vitamin D levels, indicating a mild but persistent inflammatory profile. After six months, these individuals exhibited early gingival inflammation, muscle tenderness, or mild TMJ discomfort more frequently than those with low BioRisk-S values (p < 0.01). The predictive model demonstrated good accuracy for detecting early biological imbalance preceding clinical dysfunction, with an area under the curve (AUC) of 0.84 (95% CI: 0.78–0.89). Conclusions: The BioRisk-S algorithm represents a feasible, low-cost tool for early systemic screening of functional imbalance within the stomatognathic system. By integrating routine laboratory parameters, this method may help identify individuals at risk before the onset of visible symptoms, supporting preventive and personalized approaches in oral and systemic health management. Full article

Age-related diseases such as cardiovascular disorders, neurodegeneration, and metabolic syndrome share a unifying pathological signature—persistent low-grade inflammation or “inflammaging”. Among the transcriptional regulators that orchestrate this process, RUNX1 has emerged as a pivotal molecular hub linking inflammation, cellular senescence, and tissue dysfunction. Traditionally recognized for its role in hematopoietic lineage specification, RUNX1 is now known to exert context-dependent regulatory functions across diverse organ systems. Its activation in aged tissues is driven by convergent pro-inflammatory and stress-related pathways—including NF-κB, MAPK, JAK/STAT, and oxidative signaling—that reinforce RUNX1 transcriptional activity through epigenetic reprogramming and chromatin remodeling. Sustained RUNX1 upregulation contributes to cellular senescence, fibrotic remodeling, and regenerative blockade, forming a self-perpetuating cycle of “inflammation amplification–functional decline”. In the cardiovascular, nervous, and hematopoietic systems, aberrant RUNX1 activation underlies fibrosis, neuroinflammation, and clonal hematopoiesis, respectively, establishing RUNX1 as a shared driver of age-associated pathology. The isoform-specific and temporally dynamic regulation of RUNX1 underpins its dual pro- and anti-inflammatory roles, highlighting its translational potential as both a biomarker and therapeutic target. A range of emerging intervention strategies has demonstrated promising capacity to precisely modulate RUNX1 activity. Collectively, these advances position RUNX1 at the intersection of inflammation, epigenetic instability, and tissue degeneration, opening new avenues for targeted intervention in inflammaging and age-related diseases. Full article

Background: Systemic inflammation plays a pivotal role in heart failure (HF) progression, yet no meta-analysis has synthesized prospective cohort data on interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Objectives: To quantify the independent prognostic value of IL-6, hs-CRP, and NLR for mortality and HF-related outcomes across HF phenotypes. Methods: Following PRISMA and MOOSE guidelines, we searched PubMed, Embase, Scopus, Web of Science, and CENTRAL from January 2014 to October 2025 for prospective cohorts reporting adjusted hazard ratios (HRs). Random-effects meta-analysis pooled HRs; heterogeneity was assessed via I² statistic, with subgroup and sensitivity analyses for robustness. Quality was evaluated using Newcastle–Ottawa Scale (NOS) and GRADE. Results: Thirteen cohorts (n ≈ 19,000) were included. Elevated IL-6 (five studies) was associated with increased all-cause mortality and composite outcomes (low-moderate heterogeneity, I² < 35%). hs-CRP (five studies) showed similar prognostic strength, with trajectories amplifying risk. NLR (three studies) independently predicted adverse events with negligible heterogeneity. Associations persisted across HFrEF and HFpEF, acute/chronic settings, and geographic regions, independent of natriuretic peptides and comorbidities (NOS median 8/9; GRADE moderate-to-high). Conclusions: IL-6, hs-CRP, and NLR are robust, independent prognostic biomarkers in HF, supporting their integration into clinical risk stratification and inflammation-targeted therapies. PROSPERO: CRD420251207035. Full article

Background/Objectives: A subset of individuals develops persistent symptoms following SARS-CoV-2 infection, including musculoskeletal (MSK) manifestations, a condition known as long COVID (LC). Emerging hypotheses suggest that chronic low-grade inflammation in LC may impair bone metabolism and compromise joint health. However, empirical evidence is limited, and the impact of LC on MSK health, particularly bone and joint integrity, is poorly understood. To determine the influence of LC on MSK function, including bone health, body composition, and joint integrity. Methods: A 12-month longitudinal prospective cohort feasibility study was conducted involving 45 adults with LC and 40 well-recovered (WR) post-COVID-19 controls. Baseline and follow-up assessments included dual-energy X-ray absorptiometry (DXA) for bone mineral density (BMD) and total body composition (TBC), alongside ultrasound of the hand and knee joints to evaluate intra-articular changes. Results: The LC group had more fat in the gynoid, android, and leg regions at each assessment point compared to the controls (p < 0.01). LC showed a significantly lower knee synovial hypertrophy at the baseline, 13.3% compared to WR 45% (p = 0.001), and a marginal improvement in hand synovial hypertrophy, over 12 months, from a median of 2 (IQR 1;5) to 1 (IQR 0;3) (p = 0.012), as observed via MSK ultrasound. No notable differences were found between groups regarding BMD, either in the LC group compared to the control group or overtime. Conclusions: This cohort study of LC adults and controls found no evidence of rapid bone loss; however, adiposity and joint symptoms suggest the need for ongoing monitoring. Future research should focus on MSK markers, muscle function, advanced imaging, and improving MSK health. Full article

Metastasis remains the leading cause of cancer deaths, heavily influenced by aging-related biological processes. As global life expectancy increases, cancer incidence and progression complexity in older adults also rise, emphasizing the urgent need to understand how the aging tumor microenvironment (TME) promotes metastasis. This review explores the molecular and cellular mechanisms behind metastatic development in the aged TME, focusing on the combined impacts of cellular senescence, chronic inflammation (inflammaging), immune system decline, extracellular matrix (ECM) changes, and abnormal blood vessel growth. Aging causes an accumulation of senescent cells that secrete a range of cytokines, growth factors, and enzymes (SASPs), which remodel the ECM, making it stiffer and more degradable, and activate pro-metastatic pathways like TGF-β, STAT3, and MAPK, aiding processes like EMT and tumor invasion. Meanwhile, persistent low-grade inflammation attracts immunosuppressive cells, and immune decline hampers tumor surveillance, allowing cancer cells to evade immune detection. The aged TME also undergoes significant vascular and metabolic changes, such as abnormal angiogenesis and hypoxia, supporting the growth of more aggressive, treatment-resistant cancer clones and spreading metastases. These changes are driven by hallmarks of molecular aging, including telomere shortening, oxidative DNA damage, and epigenetic alterations, which lead to genetic instability and turn the aged stroma into fertile ground for metastasis. The review also discusses new therapeutic approaches, including senolytics, anti-inflammatory treatments, immune system rejuvenation, and metabolic strategies, highlighting the importance of age-specific models and precision medicine to enhance outcomes for the growing number of elderly cancer patients. Full article

Deep venous thrombosis (DVT) is characterized by the formation of a thrombus within deep veins. The unmet need to identify new biomarkers and causal risk factors in DVT patients has led to the use of novel techniques, such as metabolite analyses. This study aimed to characterize metabolic alterations in acute DVT patients using ¹H-NMR spectroscopy and determine the persistence of these changes over a six-month follow-up. Metabolomics, particularly ¹H-NMR spectroscopy, was performed on serum samples from acute DVT patients (first 30 days from diagnosis) and healthy controls (HC). Additionally, 10 plasma markers were evaluated using a Luminex kit. A total of 30 patients, with a mean age of 44 ± 12.5 years, primarily women (9 males:21 females), were included. Acute DVT patients showed elevated inflammatory markers, such as IL-6, IL-8, PDGF-AB/BB, and P-selectin, which later decreased in the follow-up group. However, adhesion molecules like sVCAM-1 and sICAM-1 have increased after six months. Metabolomics analysis revealed significantly decreased levels of glutamine, glucose, and branched-chain amino acids (BCAAs), alongside increased lactate levels in acute DVT samples. Metabolomic profiles showed only partial normalization at follow-up, indicating persistent metabolic dysregulation. Overall, the reduced glucose metabolism and increased lactate levels indicate anaerobic metabolism, likely caused by tissue hypoxia due to impaired blood flow. Glutamine, essential for DNA, ATP, and protein synthesis, was notably reduced, potentially impairing endothelial cell proliferation and vascular repair. The presence of adhesion molecules in the follow-up group confirms persistent endothelial dysfunction. These findings suggest that metabolic and endothelial alterations may persist long after acute inflammation resolves in DVT patients. In conclusion, the persistence of metabolic dysregulation suggests chronic metabolic stress in these patients, potentially resulting from ongoing endothelial damage, low-grade inflammation, or altered mitochondrial function due to past tissue hypoxia. Full article

Background/Objectives: Long COVID (LC) causes persistent symptoms, including fatigue, musculoskeletal (MSK) pain, and a lower quality of life. It is hypothesised that chronic low-grade inflammation in LC could impact bone, joints, and muscle microcirculation, but evidence is limited. Our aim is to assess health-related quality of life (HRQoL) and circulating inflammation, bone turnover markers (BTM), and vitamin D in LC individuals to explore their potential association with MSK function. Methods: Prospective longitudinal cohort; LC n = 45, well-recovered (WR) n = 40; 12 ± 2 months follow-up. Baseline and follow-up assessments included evaluations of HRQoL and pain-rating questionnaires, and blood analysis of inflammatory and bone turnover markers (BTM). Results: More females were in the LC group. LC reported significantly lower HRQoL compared to WR, with no change over 12 months. LC had higher vitamin D levels at baseline, median 29.46 ng/mL (23.75; 35.06) compared to WR 20.36 ng/mL (15.995; 27.65) (p = 0.0021). Both groups experienced significant increases in vitamin D after 12 months: WR median from 21.4 ng/mL (16.34; 27.89) to 29.58 ng/mL (25.33; 41.74), (p =< 0.001) and LC median from 32.695 ng/mL (23.665; 35.1) to 35.89 ng/mL (30.1; 41.2), (p = 0.0023). Pain rating showed LC also experienced more hand pain at baseline median 1 (0; 5), (p = 0.003). There were no differences between groups in BTM or cytokines over time. Conclusions: This feasibility cohort showed that LC is associated with a reduction in HRQoL and joint symptoms; however, no significant changes were observed in the inflammatory markers, indicating the need for ongoing monitoring. Future studies should explore MSK, muscle function via imaging, and ways to enhance musculoskeletal health and well-being. Full article

Cancer survivors (CS) constitute an expanding population with underrecognized cardiometabolic risk. Despite substantial improvements in five-year survival rates, both childhood and adult survivors remain at high risk for premature morbidity and mortality. These risks are particularly pronounced following exposure to anthracyclines and/or chest radiotherapy, typically in a dose-dependent manner. In Chile, the establishment of the National Pediatric Antineoplastic Drug Program (PINDA) in 1998 marked a milestone in improving equitable access to high-quality pediatric oncology care through evidence-based treatment protocols across the public health system; the adult counterpart (PANDA) has developed diagnostic, treatment, and monitoring protocols for hematological neoplasms. Few prospective cohort or mechanistic studies have clarified risk stratification or surveillance strategies in survivor populations. The regulated, short-term activation of inflammation and innate immunity can be an adaptive and protective response to tissue injury, whereas persistent low-grade inflammation may trigger neutrophil extracellular traps formation (NETosis) and other maladaptive pathways that accelerate endothelial injury, thrombosis, and adverse cardiovascular remodeling. NETosis represents a putative immunomodulatory target for therapeutic immunomodulation in heart failure and maladaptive left ventricular remodeling in preclinical models. Concurrently, skeletal muscle-derived and hormonal mediators known as exerkines—together with increased NET activity—may modulate the pathophysiology of chronic cardiometabolic disease and contribute to cancer progression, particularly in the context of obesity, diabetes, and insulin resistance. Structured exercise is a promising non-pharmacological intervention that modulates inflammatory and metabolic pathways and may thereby help prevent non-communicable diseases, including cancer. We synthesize basic and clinical evidence to (1) define how cancer therapies promote low-grade inflammation and NETosis; (2) describe how exerkines and structured exercise influence cardiometabolic biology; and (3) evaluate exercise as a mechanistic and clinically pragmatic strategy to reduce long-term CVD risk in pediatric and adult CS. Full article

Crohn’s disease is a chronic inflammatory disorder with variable progression that often leads to hospitalization, treatment escalation, or surgery. While clinical and endoscopic indices guide disease monitoring, cross-sectional enterography provides unique visualization of transmural and extramural inflammation, offering valuable prognostic information. This systematic review and meta-analysis examined the prognostic significance of magnetic resonance enterography (MRE) and computed tomography enterography (CTE) in Crohn’s disease. Following PRISMA guidelines and a registered protocol, eight databases were systematically searched through August 2024. Two reviewers independently conducted data extraction, risk-of-bias assessment (QUADAS-2), and certainty grading (GRADE). Random-effects models were applied for pooled analyses. Eleven studies, including more than 1500 patients, met eligibility criteria. Across cohorts, transmural healing on enterography was consistently associated with favorable long-term outcomes, including a markedly lower need for surgery and hospitalization. Conversely, stenosis and persistent inflammatory activity identified patients at substantially higher risk of surgery, treatment intensification, or disease-related hospitalization. The certainty of evidence was high for surgical outcomes and moderate to low for other endpoints. Conventional enterography provides meaningful prognostic insight into Crohn’s disease and should be considered a complementary tool for risk stratification and treatment planning. Transmural healing represents a protective marker of a favorable disease course, whereas structural and inflammatory findings indicate patients who may benefit from closer monitoring or earlier therapeutic intervention. Full article