P-004 Anti-TNF (Infliximab) Plus mTOR Inhibitor (sirolimus) for Induction of Remission in Severe Steroid—Refractory Ulcerative Colitis
Bibliographic record
Abstract
Ulcerative colitis (UC) is an inflammatory and autoimmune disease, characterized by increased cell proliferation, activation of T cells, production of proinflammatory cytokines and leukocyte infiltration. Some compounds have shown antiproliferative therapeutic effect in UC murine models. Sirolimus inhibits mTOR (mammalian target of rapamycin) which is a serine / threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. Inhibition of mTOR has shown a significant decrease in the Disease Activity Index (UC-DAI), leukocyte infiltration and damage of the crypts in the colonic mucosa. However, there is no evidence of cooperative effect to induce remission when added sirolimus to an anti-TNF (chimeric anti-tumor necrosis factor-α antibody with a potent anti-inflammatory effect) in patients with severe steroid-refractory UC. A 30 year old man, with a 12 year history of severe UC (Truelove & Witts severity index) with an average of 10 watery stools a day accompanied by blood. Initially hemoglobin (Hb) was 10 g/dL and erythrocyte sedimentation rate (ESR) 32 mm/hr. Colonoscopy showed complete left sided involvement, marked erythema, friability, erosions, ulcerations and spontaneous bleeding (Mayo Clinic index score 12 points, Montreal Classification S3 E2). The patient has been treated with mesalazine and prednisone achieving short partial remissions (as the best response reached), during the first 8 years of evolution of the disease he has suffered frequent periods of exacerbation and a toxic megacolon event. The past 6 months have dramatically increased the severity and the number of evacuations (20 liquid-stools a day and sometimes only blood-stools), abdominal pain but with no satisfactory response to steroids. He had also severe iron-deficiency anemia (Hb 4.5 g/dL, Mean Corpuscular Volume 71 fl and ESR 40 mm/hr) requiring erythrocyte transfusions and intravenous iron. Infliximab 5 mg/kg was initiated once a week showing partial improvement of symptoms, therefore after 2 weeks, Sirolimus 2 mg/day was added, showing extraordinary improvement of symptoms, with reduction in the number of stools (1-2 daily) no bleeding or pain, Hb 14 g/dL and ESR 18 mm/hr, fulfilling clinical criteria for complete remission. He completed a total of 8 cycles of Anti TNF and continued sirolimus as maintenance, keeping an excellent evolution. Case report described above. Case report described above. Comprehensive treatment of patients with severe UC, including intravenous iron, supportive measures and this case shows that the addition of a mTOR inhibitor to anti-TNF could be a suitable combination for the induction of a complete remission in UC. It will require to be tested in a large group of patients with severe steroid-refractory disease.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".