Centre Hospitalier Universitaire de Liège

Vedolizumab has become the preferred first-line advanced therapy in ulcerative colitis (UC). However, the optimal second-line treatment following vedolizumab failure remains unclear. We aimed to evaluate the effectiveness and safety of second-line therapies after first-line vedolizumab. We conducted a multicenter retrospective study including UC patients from 31 centers who received infliximab (IFX), subcutaneous (SC) anti-TNFs, or ustekinumab after vedolizumab failure. The primary endpoint was steroid-free clinical remission (SFCR) at week 14. Predictors of remission were identified using multivariate logistic regression. Among 196 patients, 99 received IFX, 27 anti-TNF SC, and 70 ustekinumab. At week 14, SFCR was achieved in 78 patients (39.8%): 38 (38.4%) with IFX, 8 (29.6%) with anti-TNF SC, and 32 (45.7%) with ustekinumab, with no significant difference between groups (p=0.32). Median treatment persistence ranged from 8 to 9.2months. Baseline corticosteroid use was associated with lower odds of SFCR (OR=0.37, 95% CI [0.18-0.73]). Adverse events occurred in 15.8% of patients, including 12.2% serious events. Overall adverse events were less frequent with ustekinumab than with IFX (10.0% vs. 24.2%, p=0.02), while serious events were comparable (5.7% vs. 16.1%, p=0.08). Discontinuation due to adverse events was more frequent with IFX (12.1%) and anti-TNF SC (14.8%) than with ustekinumab (2.9%, p=0.045 and 0.049). In UC patients failing vedolizumab, second-line IFX, anti-TNF SC, and ustekinumab showed similar effectiveness and persistence. Infliximab remains a robust option for rapid control in high inflammatory burden, whereas ustekinumab may be preferred for its superior safety profile in high-risk patients.

Serum total alkaline phosphatase (ALP) is a robust predictor of all-cause mortality in both the general population and in patients with chronic kidney disease (CKD). Individual ALP isozymes and isoforms exert specific physiological functions and may therefore inform separately on different disease processes and risks related to these. Serum ALP consists predominantly of bone and liver isoforms, with a smaller contribution from the intestinal isoenzyme. We aimed to characterize the impact of CKD on serum ALP fractions and to identify clinical and biochemical correlates. Serum ALP liver, bone and intestinal fractions were analysed by electrophoresis in 523 individuals across stages of CKD (stage G1-2: n=90; G3: n=100; G4-5: n=139; G5D: n=194) and in 21 kidney-healthy controls. Associations with demographics and parameters of mineral metabolism and inflammation were examined. In haemodialysis patients, we further explored the association between ALP isozymes and all-cause mortality. Total ALP levels increased significantly across stages of CKD, with liver, bone and intestinal fractions all contributing. In patients with CKD G5D, circulating levels of all three fractions were more than two-fold higher than in controls. Bone ALP associated with PTH while liver ALP associated with C-reactive protein, both independent of demographics and kidney function. Higher liver ALP levels associated with increased mortality risk, independent of traditional risk factors and inflammation. In patients with CKD, elevations in liver, bone and intestinal ALP fractions reflect distinct biological pathways and may differentially inform on risk related to different disease processes. While bone ALP reflects bone metabolism, liver ALP is linked with inflammation. The elevation in CKD and the independent association of liver ALP fraction with mortality in patients treated with haemodialysis calls for additional clinical and mechanistic studies.

Cancer Predisposition Syndromes (CPS) are heritable genetic conditions associated with an increased risk of developing various cancers throughout life. While early identification and tumour surveillance can improve outcomes, CPS are often underdiagnosed in clinical practice. To evaluate clinicians' perspectives and identify barriers to CPS identification and care across Europe, we conducted the SCOPE study: a three-part cross-sectional survey of paediatric haematology/oncology professionals, followed by a modified Delphi consensus process with members of the SIOP Europe Host Genome Working Group. A total of 185 paediatric oncologists from 22 countries participated in the survey. More than 40% of participants reported low or uncertain confidence across different CPS-related tasks, particularly in counselling families (64.3%) and interpreting germline genetic findings (57.3%). Access to clinical geneticists and dedicated CPS clinics were predictors of higher confidence for some domains, while individual experience and institutional patient volume had limited influence. Regular use of universal CPS screening tools was low (42.3%), with most clinicians relying on personal judgement rather than structured criteria. The most cited barriers were lack of screening guidelines (57%) and difficulties in interpreting results (35.1%). Regular training and workshops, availability of genetic counsellors or educators for patient support, and patient-friendly education material were most cited as areas of improvement. The Delphi process led to three recommendations: (1) improve clinician training and communication strategies, (2) integrate CPS screening into standard treatment plans, and (3) develop accessible, patient-centred educational materials. These recommendations highlight opportunities to enhance CPS care through structured support, interdisciplinary collaboration, and systematic screening approaches.

BackgroundTo develop a 10-year risk score to predict lower-limb amputation (LLA) in individuals with type 1 diabetes, and to assess whether this score also predicts kidney failure, and cardiovascular disease (CVD).MethodsThe LLA risk score was derived from GENEDIAB and GENESIS, two prospective French and Belgian cohorts of 828 individuals with type 1 diabetes. External validation was assessed in SURGENE, an independent cohort of 247 individuals with type 1 diabetes. LLA was defined as a non-traumatic amputation above the metatarsophalangeal joint, kidney failure as the need for renal replacement therapy, transplantation, or an estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m2, CVD as the occurrence of myocardial infarction, heart failure, or stroke, and major adverse cardiac event (MACE) as a composite of myocardial infarction, stroke, heart failure, or all-cause death.ResultsDuring 12 years of follow-up, LLA, kidney failure, CVD and MACE occurred in 71 (9%), 84 (11%), 138 (17%) and 265 (32.0%) of participants, respectively. Sex, diabetes duration, prior LLA, eGFR, and albuminuria were identified as independent determinants of incident LLA and were used to construct the risk score. Compared to participants in the lowest score, those in the highest score had a significantly increased risks of LLA (multivariable-adjusted HR 6.02 [95% CI, 1.92–18.89]), kidney failure (8.97 [3.95–20.37]), CVD (2.50 [1.34–4.64]) and MACE (1.91 [1.24–2.96]). The score demonstrated good discriminative performance for LLA (C-index 0.82 [0.77–0.87]), kidney failure (0.86 [0.82–0.91]), CVD (0.73 [0.68–0.78]), and MACE (0.71 [0.68–0.75]). Similar predictive performance was observed in the validation cohort.ConclusionThis newly developed 10-year LLA risk score achieved excellent ability to identify individuals with type 1 diabetes at high risk for LLA, kidney failure, CVD, and MACE.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s12933-025-03056-1.

Type 2 diabetes mellitus (T2DM) is common in patients with chronic kidney disease (CKD). Both conditions associate with an increased fracture risk, with proposed etiology including impaired bone quantity and quality. This cross-sectional study examined the bone phenotype in patients with T2DM and kidney failure and explored the role of glycemic control on the bone phenotype. To do so laboratory parameters of mineral metabolism (including sclerostin) and bone turnover markers (BTM) (bone-specific alkaline phosphatase (BALP), trimeric pro-collagen type I N-terminal propeptide (intact PINP) and tartrate-resistant acid phosphatase isoform 5b (TRACP5b)) were assessed in 647 patients with kidney failure, of which 102 had T2DM (median hemoglobin A1c (HbA1c) of 6.2%), at time of kidney transplantation. Patients with type 1 DM were excluded. Bone mineral density (BMD, n = 555) by densitometry, and bone histomorphometry (n = 188) were available for subsets, and correlations between HbA1c and both BTM and BMD were examined. This study found that intact PINP was lower (68 vs. 82μg/L, p = .03) while sclerostin was higher (2.1 vs. 1.8ng/mL, p = .04) in T2DM versus non-T2DM in unadjusted analysis. BMD at the lumbar spine (Z-score - 0.066 vs. -0.760, p < .001) and femoral neck (Z-score - 0.680 vs. -0.965, p = .04) were higher in T2DM, and T2DM was in multivariable regression analysis identified as a significant determinant of lumbar spine BMD, independent of age, sex, and BMI. Bone histomorphometric parameters did not differ between groups. A correlation between HbA1c and BTM and BMD was present, but only in non-T2DM (BALP (ρ = -0.12, p = .007), intact PINP (ρ = 0.14, p = .002), TRACP5b (ρ = -0.13, p = .003), BMD at lumbar spine (ρ = 0.12, p = .008), femoral neck (ρ = 0.11, p = .02), and total hip (ρ = 0.17, p < .001)). In conclusion, patients with kidney failure and T2DM have preserved BMD compared to patients without diabetes. Our findings suggest a role for hyperglycemia as a determinant of the bone phenotype.