Search Results (3,573)

Biomarkers that predict disease progression and treatment-free remission (TFR) would be of significant clinical value in chronic myeloid leukaemia (CML). We have previously shown that CIP2A levels at diagnosis can identify patients at increased risk of progression. One mechanism by which CIP2A acts is through upregulation of the anti-apoptotic gene BCL-XL. In this study, we evaluated BCL-XL mRNA expression as a diagnostic biomarker using samples from the SPIRIT2 and DESTINY clinical trials. In SPIRIT2, which compared imatinib and dasatinib as first-line therapies, high BCL-XL expression was associated with treatment failure, poor early molecular response, and lower rates of MR2 and MR3 achievement in patients treated with imatinib. In the DESTINY trial, which assessed treatment de-escalation and discontinuation, BCL-XL expression was significantly higher in patients who experienced molecular relapse compared to those achieving sustained TFR. Notably, increases in BCL-XL were detectable 6 to 8 months prior to molecular relapse, suggesting it may serve as an early biomarker of unsuccessful TFR. We now propose a clinical diagnostic toolkit combining CIP2A and BCL-XL biomarkers to stratify CML patients by the risk of disease progression and likelihood of achieving successful TFR. Full article

Background: Clinical remission has become a realistic treatment goal in severe asthma, but current evidence mostly reports global remission rates without accounting for baseline disease burden. No simple tool exists to quantify baseline severity and estimate an individual patient’s probability of achieving remission under biologic therapy. Methods: This prospective observational study included 93 adults with severe asthma initiating tezepelumab across 14 specialised severe asthma units in Spain. Four baseline domains—poor symptom control (ACT < 20), ≥1 severe exacerbation in the previous 12 months, maintenance oral corticosteroid (OCS) use, and FEV₁ < 80% predicted—were used to construct an empirically weighted composite score (Base4Score) based on the inverse probability of correcting each abnormal domain at 12 months. Strict clinical remission at 12 months was defined as ACT ≥ 20, no severe exacerbations, no maintenance OCS, and FEV₁ ≥ 80%. Logistic regression was used to assess the association between the score and non-remission, adjusting for age, sex, smoking status, T2 phenotype, and biologic-naive status. Results: Of 93 treated patients, 81 had complete baseline data for Base4Score derivation and 77 had complete 12-month data for strict clinical remission analysis. Strict clinical remission was achieved in 16/77 patients (20.8%). Remission rates decreased across increasing baseline score strata: 40.0% for scores < 5, 17.6% for scores 5 to <9, and 12.5% for scores ≥ 9 (linear p-trend = 0.022). Each 1-point increase in the continuous Base4Score was associated with higher adjusted odds of non-remission (OR 1.22; 95% CI 1.00–1.49; p = 0.047), and patients with scores ≥ 9 had approximately sevenfold higher adjusted odds of non-remission than those with scores < 5 (OR 6.77; 95% CI 1.40–32.84; p = 0.018). Conclusions: The Base4Score is a simple, empirically derived baseline severity index that predicts 12-month strict clinical remission in severe asthma treated with tezepelumab. If externally validated, it could help personalise expectations, optimise timing of biologic initiation and guide treat-to-target strategies in severe asthma. Full article

Background/Objectives: Allogeneic hematopoietic stem cell transplantation is associated with increased cardiovascular risk driven by endothelial dysfunction, chronic inflammation, and treatment-related metabolic disturbances, including dyslipidemia. In the contemporary era of post-transplant cyclophosphamide-based prophylaxis, the prognostic significance of dyslipidemia—particularly as assessed by non-HDL cholesterol—remains unclear. In this study, we aimed to compare the engraftment days, graft-versus-host disease (GVHD) development, relapse, overall survival rates, and cardiovascular mortality in patients using myeloablative/reduced intensity conditioning regimens with post-transplant cyclophosphamide (PTCy) 50 mg/kg/day for 2 days in patients with acute leukemias. Methods: A total of 95 adult patients with acute leukemias were included in their first remission who underwent matched sibling donor transplantation with PTCy (50 mg/kg on days +3 and +4). Patients were stratified according to pre-transplant non-HDL-C levels (<160 mg/dL vs. ≥160 mg/dL). Matched related donors were selected for the patients. All patients received either myeloablative or reduced-intensity conditioning based on EBMT criteria, with fludarabine-based combinations including busulfan, treosulfan, or TBI, along with ATLG administered at a total dose of 15 mg/kg. Peripheral blood stem cells were used for all transplants, and GVHD prophylaxis consisted of cyclosporine. Results: Platelet (median 13 vs. 14 days) and neutrophil (median 14 vs. 15 days) engraftment times and veno-occlusive disease (VOD) rates were comparable across groups (all p > 0.05); cumulative incidences of grade II–IV aGVHD at +100 days, grade III–IV aGVHD at +100 days, and moderate-severe cGVHD at 1 year, relapse-free survival, and non-relapse mortality at 1 year were comparable in two cohorts (all p > 0.05). GVHD-free/relapse-free survival (GRFS) at 1 year was also comparable across groups (p = 0.15). Median GRFS was 150 (95% CI: 120–330) days and 270 (95% CI: 154-not reached) days, respectively [HR was 0.68 (0.40–1.15), p = 0.15; GRFS at 1 year was 66.6% vs. 52.0%, respectively]. The groups were also comparable in terms of overall survival (OS). Follow-up ranged from 0.5 to 108 months, and median follow-up was 60 months in two cohorts. Median OS was not reached in non-HDL-C < 160 (95% CI: 70 months–not reached) and 67 months in non-HDL-C ≥ 160 groups (95% CI: 13 months–not reached) (Log rank = 0.21). No cardiovascular death events occurred during the follow-up period. Conclusions: In this homogeneous matched sibling donor transplant cohort with extended follow-up and uniform administration of post-transplant cyclophosphamide, cyclosporine-based GVHD prophylaxis, and anti-thymocyte lymphoglobulin (ATLG), pre-existing dyslipidemia was not associated with an adverse impact on GRFS, NRM, PFS, CMV reactivation, OS or long-term cardiovascular mortality. Full article

Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization. Results: 1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols. Conclusions: RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence. Full article

Programmed death-ligand 1 (PD-L1) expression is routinely used to guide immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC), yet clinical benefit remains heterogeneous even among PD-L1–high tumors. Liquid biopsy based on cell-free DNA (cfDNA) enables minimally invasive, real-time monitoring of tumor evolution. We report four cases of metastatic lung adenocarcinoma treated with atezolizumab, integrating longitudinal whole-exome sequencing (WES) of cfDNA with radiological assessment. Four patients with PD-L1–positive (≥60%) metastatic NSCLC received atezolizumab monotherapy. Serial cfDNA samples (1–3 per patient) were analyzed by high-depth WES. Distinct molecular trajectories paralleled divergent clinical outcomes. One patient achieved a complete molecular response, characterized by progressive clearance of KRAS, ATM, and NF1 mutant clones, which was concordant with radiological remission. A second patient showed an initial molecular response, followed by clonal rebound of TP53, NF1, and NOTCH2 mutant populations and the emergence of PTEN and KIF1A variants, suggesting clinical progression. Two patients exhibited primary resistance despite high PD-L1 expression, with persistent or expanding clones and early subclonal diversification; in one case, new EGFR and BRAF alterations emerged under treatment pressure. Notably, switching to platinum-based chemotherapy in a non-responder induced a measurable molecular response, highlighting discordance between PD-L1 status and immunotherapy efficacy. Longitudinal cfDNA WES captured dynamic clonal remodeling under immunotherapy and anticipated radiological outcomes. These findings underscore the clinical necessity of integrating dynamic molecular monitoring by liquid biopsy to overcome the limitations of static PD-L1 assessment, refine therapeutic stratification, and identify early resistance mechanisms in advanced NSCLC. Full article

Background/Objectives: Histologic remission has emerged as a key treatment target in inflammatory bowel disease (IBD), but routine assessment requires repeated endoscopy and biopsies. Blood-based indices reflecting inflammation, nutritional status and atherogenic risk are inexpensive and widely available, yet their integrated contribution to histologic activity remains unclear. This study addresses this gap by simultaneously analyzing a broad panel of 44 variables—including nutritional status indicators, CBC-derived inflammation indices, and atherogenic lipid indices—in IBD patients. Methods: In this retrospective study, 100 patients with IBD (50 Crohn’s disease [CD], 50 ulcerative colitis [UC]) without additional comorbidities and with concomitant histologic assessment were analyzed. Histologic activity was coded as active vs. remission. At the time of biopsy, the complete blood count, biochemistry and lipid profile were used to calculate immuno-nutritional indices (CONUT score, prognostic nutritional index), inflammatory indices (neutrophil-to-platelet ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio [LMR], systemic immune-inflammation index, systemic immune-inflammation index, systemic inflammation response index [SIRI], aggregate index of systemic inflammation, C-reactive protein to albumin ratio) and atherogenic indices (atherogenic index of plasma [AIP], triglyceride-to-HDL cholesterol ratio). Variable selection was performed separately for CD and UC using least absolute shrinkage and selection operator (LASSO) regression and sparse partial least squares discriminant analysis (sPLS-DA). Independently associated predictors were then entered into multivariable logistic regression models, and their discriminative performance was evaluated using ROC analysis with bootstrap-derived 95% confidence intervals. Results: LASSO analysis identified a broadly similar systemic profile associated with histologic activity in CD and UC, dominated by the CONUT score, SIRI, AIP, LMR and red blood cell parameters, whereas demographic features and most routine biochemical markers were shrunk towards zero. Cross-validated AUCs for the LASSO models were 0.93 in CD and 0.87 in UC. sPLS-DA confirmed this pattern: CONUT, SIRI and AIP consistently showed the highest variable importance in projection scores and loadings on the first latent component. In multivariable regression, the CONUT score, SIRI and AIP remained independent predictors of histologic activity in CD, while hematocrit, CONUT score, SIRI and AIP were independently associated with histologic activity in UC. In ROC analysis, AUCs for CONUT, SIRI and AIP were 0.81, 0.89 and 0.87 in UC, and 0.72, 0.82 and 0.83 in CD, respectively. Conclusions: Histologic activity in IBD is characterized by a coupled systemic profile in which immuno-nutritional compromise (captured by CONUT) forms the core signal, supplemented by systemic inflammation (SIRI) and atherogenic dyslipidemia (AIP). These readily available blood-based indices may help to approximate histologic disease activity in clinical practice. However, considering that comorbid diseases may affect these indices, the strict exclusion criteria applied in this study may limit the generalizability of the findings among patients with IBD. Consequently, further validation in larger prospective cohorts is warranted. Full article

Background and Clinical Significance: Mixed-phenotype acute leukemia (MPAL) is a rare hematologic malignancy characterized by the co-expression of myeloid and lymphoid markers and is associated with poor prognosis. Myeloid sarcoma (MS), particularly in the mediastinum, is an uncommon extramedullary manifestation and is rarely reported in association with MPAL. Case Presentation: We report a rare case of mediastinal MS with biphenotypic features and pericardial extension occurring concurrently with MPAL, highlighting diagnostic challenges, therapeutic strategies, and long-term outcomes. We describe the clinical course, diagnostic workup, treatment, and follow-up of a 21-year-old woman who presented with cardiac tamponade secondary to a mediastinal mass. Histopathology and immunophenotyping established the diagnosis of mediastinal MS associated with MPAL (B/myeloid, NOS). Management included surgical cytoreduction, intensive induction chemotherapy, and consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor. Fertility preservation with oocyte retrieval, in vitro fertilization (IVF), and embryo cryopreservation was performed prior to conditioning. A focused literature review of MPAL cases with extramedullary involvement was conducted. The patient achieved complete remission following induction therapy and underwent allo-HSCT. Despite the historically poor prognosis of mediastinal MS and MPAL, she remains in sustained complete remission 13 years after diagnosis. A literature review identified only eight reported cases of MPAL with extramedullary disease, with mediastinal involvement described in a single case and allo-HSCT performed in only two patients. Conclusions: This case illustrates a rare presentation of MPAL with mediastinal myeloid sarcoma and cardiac tamponade, demonstrating that aggressive multimodal therapy including allo-HSCT may achieve durable remission even in high-risk presentations. Early multidisciplinary management and consideration of fertility preservation are essential in young patients. Full article

Multicentric reticulohistiocytosis (MRH) is a rare systemic histiocytic disorder of uncertain etiology characterized by papulonodular cutaneous lesions and potentially destructive polyarthritis, with variable multisystem involvement. Owing to its low prevalence, evidence for optimal management remains limited, and treatment responses are heterogeneous. Emerging reports suggest that Janus kinase (JAK) inhibition may provide benefit in refractory disease. We report a 60-year-old woman with MRH presenting with papulonodular skin lesions, symmetric polyarthritis, constitutional symptoms, and interstitial lung disease (nonspecific interstitial pneumonia pattern) in the context of co-existing primary biliary cholangitis and no evidence of malignancy. Prior therapies (glucocorticoids, methotrexate, leflunomide) achieved suboptimal control. Upadacitinib, a selective JAK1 inhibitor, induced rapid and complete remission of cutaneous and articular disease with improvement of pulmonary involvement. Secondary weight gain and incident diabetes were managed with tirzepatide. This case adds to the limited literature supporting JAK inhibition as a targeted option for refractory MRH, including multisystem disease with pulmonary involvement. Systematic evaluation of efficacy, durability, and safety is warranted. Full article

Background: Severe asthma remains associated with substantial morbidity despite optimized inhaled therapy. Biologic agents targeting type 2 inflammation improve clinical outcomes; however, real-world evidence regarding the durability of these effects beyond the first treatment year remains limited. The present study extends the follow-up of a previously reported real-world cohort in which 12-month outcomes of biologic therapy were evaluated. Methods: We conducted a retrospective observational longitudinal study of adults with severe asthma treated with omalizumab, benralizumab, or dupilumab at a tertiary center in Târgu-Mureș, Romania, between 2020 and 2025, extending follow-up of a previously published real-world cohort. The same patient cohort was followed for an additional period, with longitudinal data collected up to 24 months after biologic therapy initiation. Clinical, functional, and biomarker outcomes were assessed at baseline, 12 months, and 24 months, including Asthma Control Test (ACT) score, forced expiratory volume in one second (FEV₁% predicted), annual exacerbation rate, blood eosinophil count, and fractional exhaled nitric oxide (FeNO). Remission was defined as clinical (ACT ≥ 20, no severe exacerbations, and no maintenance oral corticosteroids), biological (FeNO < 20 ppb and blood eosinophils < 150/µL), and complete (both clinical and biological). Longitudinal changes were analyzed using the Friedman test with post hoc Wilcoxon signed-rank tests. Results: Forty-eight patients were included at baseline, and 41 had available data at 24 months. ACT scores improved from 12 (IQR 11–14) at baseline to 23 (21–25) at 12 months and remained stable at 22 (20–25) at 24 months (p < 0.001). Predicted FEV₁% increased from 50 (39–59) to 78 (68–88) at 12 months and 79 (66–96) at 24 months (p < 0.001). Blood eosinophil counts were markedly suppressed, and FeNO levels continued to decrease over time. Exacerbations declined from 2 (2–3) per year at baseline to 0 and 0.5 (0–1) at 12 and 24 months, respectively (p < 0.001). At 24 months, clinical, biological, and complete remission were observed in 61.0%, 78.0%, and 41.5% of patients with available paired data, respectively. Conclusions: Biologic therapy was associated with sustained clinical and functional improvement over 24 months, accompanied by sustained improvement in type 2 airway inflammation and increasing proportions of patients meeting remission criteria in real-world practice. Full article

For decades, induction treatment of acute myeloid leukemia consisted of intensive chemotherapy for induction. High relapse rates and severe toxicity resulted in a five-year overall survival of ~30%. In patients ineligible for intensive treatment, hypomethylating agents (HMA) could be administered but generally failed to induce durable remissions. These limitations have driven the development of targeted drugs and less toxic therapeutic regimens. In the past decade, fourteen new agents have gained FDA and/or EMA approval, including small-molecule inhibitors targeting FLT3, IDH1, IDH2, BCL-2, menin, and the hedgehog pathway, as well as a CD33-directed antibody-drug conjugate. The combination of targeted drugs with intensive chemotherapy or HMA has resulted in improved remission rates and prolonged survival in certain patient subpopulations. However, many promising combinations are currently being evaluated in randomized trials and are not yet available in clinical routine. A combination that has become standard of care is HMA plus venetoclax for patients unfit for intensive chemotherapy, achieving high remission rates with relatively manageable toxicity. Moreover, targeted drugs directed against FLT3 and IDH1 have been approved in combination with intensive chemotherapy and HMA, respectively. Clinical decision-making requires rapid molecular diagnostic testing, assessment of a patient’s fitness for intensive chemotherapy, and management of toxicities and drug interactions. This narrative review, illustrated with patient vignettes, summarizes currently available therapies, guides through the latest trials on frontline combinations in AML, and provides a preview of how the therapeutic landscape may evolve in the near future. Full article

Background: Acute myeloid leukemia (AML) with CBFB::MYH11 fusion and myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are genetically defined and typically mutually exclusive entities. Case Presentation: We report a unique case of de novo AML harboring two clonal, transcriptionally active class-defining fusions: CBFB::MYH11 and GOLGA4::PDGFRB. A 61-year-old woman presented with leukocytosis with neutrophilia, eosinophilia, and monocytosis; circulating blasts; and a markedly hypercellular marrow. Cytogenetic analysis revealed inv(16)(p13.1q22) and t(3;5)(p21;q32) in all 20 metaphases, and RNA sequencing confirmed expression of both CBFB::MYH11 and GOLGA4::PDGFRB fusions. In addition, an oncogenic WT1 frameshift variant was identified. Hematopathologic findings were largely consistent with AML with CBFB::MYH11 fusion but exhibited features reminiscent of PDGFRB-rearranged MLN-TK. The patient achieved complete remission following the standard 7 + 3 induction chemotherapy regimen for AML with gemtuzumab ozogamicin. Conclusions: This case illustrates the diagnostic challenges posed by concomitant class-defining alterations in hematologic neoplasms and underscores the importance of integrated genomic assessment. Full article

This article examines a decisive yet relatively understudied stage in the canonization process of Francis Borgia, third superior general of the Society of Jesus, by focusing on the remission phase carried out between 1649 and 1655. Although Borgia had been beatified in 1624, the path toward his canonization extended over several decades, shaped by a combination of institutional, political, and procedural factors that slowed its progress. The pontificate of Innocent X marked a turning point, creating favorable conditions for renewed momentum within the Roman Curia. Following authorization by the Congregation of Rites, the remission phase formally commenced in 1649, leading to a series of witness examinations conducted in key Iberian centers—Toledo, Madrid, and Valencia—beginning in 1650. By analyzing the selection of witnesses in each location and the substance of their testimonies, the article sheds light on the strategies employed to consolidate Borgia’s reputation for sanctity and to address juridical expectations in Rome. Particular attention is given to the coordination between local ecclesiastical authorities and the central institutions of the Holy See. The study argues that the efficiency and coherence of this phase, culminating in the issuance of the remission briefs in 1655, played a crucial role in advancing the cause toward its successful conclusion in 1670. Full article

Recent evidence suggests that type I interferon (IFN) activity has prognostic relevance in systemic lupus erythematosus (SLE). This study investigated whether combining IFN activity with elevated peripheral blood plasmablast (PB) levels—another key feature of lupus pathophysiology—improves risk stratification for poor clinical outcomes. Clinical data were prospectively collected at a single lupus center. Flow cytometry was performed on freshly isolated peripheral blood mononuclear cells to investigate Sialic acid-binding Immunoglobulin-like Lectin 1 (SIGLEC-1) as a surrogate marker of IFN activity, alongside CD19⁺CD20⁻CD27^highHLA-DR⁺ PB frequencies. A total of 1276 samples from 121 patients were analyzed. At baseline, 48.8% of patients exhibited high IFN activity, including 27.3% with concurrent elevation in IFN and PB activity and 21.5% with isolated IFN activity. Patients with simultaneous IFN and PB activity showed higher anti-dsDNA antibody levels, were less frequently in DORIS remission (24.2% vs. 50.0%) and required higher daily prednisolone dosages (6.3 vs. 2.0 mg) than those with isolated IFN activity. During a median follow-up of 4.5 years (range 0.8–6.6), these patients experienced more flares (132 vs. 54, OR 1.42), required longer to achieve remission (median 399 vs. 140 days), and had a higher median time-adjusted prednisolone dose (5.6 vs. 3.0 mg). Concurrent elevation in IFN and PB activity identifies SLE patients with a poorer prognosis compared to isolated IFN activity. These findings suggest that combined IFN and PB assessment may improve prognostic stratification and support personalized treatment strategies in SLE. Full article

Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits—features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G>A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg/dL; creatinine clearance 122 mL/min) with stable sub-nephrotic proteinuria (0.52 g/day; 16 mg/m² per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring. Full article

Diet is a major modifiable determinant of gastrointestinal (GI) health, influencing disease risk and progression through coordinated effects on the gut microbiome, immune regulation, epithelial barrier integrity, oxidative balance, and epigenetic mechanisms. This narrative review synthesizes epidemiological, mechanistic, and clinical evidence from the past decade to examine bidirectional relationships between dietary patterns and seven common GI disorders: celiac disease, irritable bowel syndrome (IBS), Crohn’s disease, ulcerative colitis, Helicobacter pylori-associated gastritis, peptic ulcer disease, and lactose intolerance. Western dietary patterns, characterized by high intake of ultra-processed foods and saturated fats and low fiber consumption, are consistently associated with microbial dysbiosis, impaired barrier function, and enhanced inflammatory signaling. In contrast, Mediterranean and plant-forward dietary patterns show protective associations across multiple GI conditions. Mechanistically, diet influences GI pathophysiology largely through microbiome-derived metabolites, particularly short-chain fatty acids, which regulate epithelial homeostasis, immune tolerance, and inflammatory pathways. Condition-specific dietary strategies remain clinically important. Gluten exclusion is essential in celiac disease, low- fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) approaches provide evidence-based symptom control in IBS, and exclusive enteral nutrition or targeted exclusion diets support remission induction in Crohn’s disease. Selected probiotics and emerging postbiotics may provide adjunctive benefits in specific contexts. Despite growing evidence, dietary research remains limited by methodological heterogeneity and interindividual variability. Precision nutrition approaches integrating microbiome profiling and artificial intelligence represent a promising translational direction. Overall, dietary patterns—rather than isolated nutrients—form the foundation of GI dietary therapy. Full article