Centre Hospitalier De Roubaix

While this strategy is frequently used for other biologics, real-world evidence on subcutaneous (SC) vedolizumab (VDZ) dose intensification in inflammatory bowel disease (IBD) is lacking. This study aimed to assess the effectiveness and safety of SC VDZ intensification.

We conducted a retrospective study in 25 centers including all patients with active ulcerative colitis (UC) or Crohn’s disease (CD) (defined by PRO2), and incomplete or loss of response to SC VDZ 108 mg every other week (EOW) when the drug was intensified. The primary outcome was steroid-free clinical response (SFCr) defined by at least 50% of PRO2 improvement, no treatment change, no surgery, and SC VDZ persistence at 3 months.

Of the 154 included patients (66% UC, 34% CD), prior anti-tumor necrosis factor (anti-TNF) exposure was reported in 85% of CD and 50% of UC patients. SC VDZ was intensified for an incomplete response in 73% of CD and 53% of UC patients, mostly at 108 mg weekly (95%). At 3 months, SFCr was achieved in 35% of CD and 43% of UC patients. In multivariate analysis, factors associated with response were secondary loss of response in CD, and prior anti-TNF exposure in UC. At 12 months, 51% of CD and 37% of UC patients maintained SC VDZ. Adverse events occurred in 10 patients including one severe pneumonia and one angioedema.

In this real-world study evaluating SC VDZ intensification, an SFCr was observed in at least one-third of IBD patients at 3 months, suggesting the benefit of this strategy in clinical practice.

Transcutaneous neurostimulation (TENS) is commonly used in the treatment of chronic radicular pain, but without any consensus on the type of current to be delivered. The aim of this study was to compare the conventional high-frequency, low-intensity current called c-TENS with a mixed current called m-TENS, combining c-TENS with a low-frequency, high-intensity current.

This was a single-blind, two-period crossover randomized trial. Included patients had chronic (≥3months), neuropathic (dn4≥4) radicular pain of at least moderate intensity (Visual Analogic Scale [VAS]≥40mm [0-100mm]). Patients were randomized to receive either c-TENS or m-TENS first, then the other, and both during one month. The primary outcome was the level of radicular pain, measured by VAS at the end of each of the two period.

Seventy-four patients were included (mean age: 51.9±13.5years, female proportion: 65.6%). The mean duration of radicular pain was 45.2±51months and the mean radicular intensity was 67±12.5/100mm. After one month of treatment, VAS decreased to 53.9±20.1mm under c-TENS and to 53.9±21.3 under m-TENS (NS). Thirteen patients (20.3%) had a VAS<40/100 with either c-TENS or m-TENS (NS). Tolerance was the same for the two modes. Twenty-nine patients (46%) designated c-TENS as the most effective mode, and 34 patients (54%) designated m-TENS.

This study shows no difference in terms of efficacy or tolerance between c-TENS and m-TENS. There is no justification for preferring one of these two modes over the other for the treatment of chronic neuropathic radicular pain.

Ciliopathies are rare genetic diseases marked by considerable phenotypic heterogeneity and overlap. Among the key mechanisms of cilium biology, its compartmentalization is achieved through gating complexes and active transport such as intraflagellar transport (IFT). Among the IFT components, IFT27 plays a role in BBSome-mediated transport of ciliary membrane proteins required for ciliary signaling. While this gene was first linked to Bardet-Biedl syndrome, we next expanded its phenotypic spectrum to a fetal lethal ciliopathy. Here, we identified a second fetal case with short ribs, polydactyly, hypodysplastic kidneys, imperforate anus, and situs inversus. Genome sequencing identified novel biallelic variants in IFT27. Functional analysis of tissues from both fetal cases revealed that all the identified variants lead to mRNA decay. Immunohistochemistry on fetal kidney sections showed that those variants are associated with altered ciliogenesis. Overall, we showed that complete loss of IFT27 function leads to a severe phenotypic spectrum overlapping with short ribs polydactyly and Pallister-Hall syndromes. In addition, our results argue for a role of IFT27 in ciliogenesis in humans.