SUMMARY BackgroundSevere and severe/complicated Clostridium difficile infection (CDI) can result in ICU admission, sepsis, toxic megacolon and death. In this setting, colectomy is the standard of care but it is associated with a 50% mortality.
The overall CDI cure rates were high, with a large percentage of patients experiencing clinical improvement of their IBD after FMT. A minority of patients developed an IBD flare. No severe adverse events directly attributable to FMT were found in this largest reported series of recurrent or refractory CDI patients with concurrent IBD.
Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.
Modification of /3-lactam nuclei has been limited only by the stability of the nucleus and the imagination of the medicinal chemist. In our exploration of the enhanced stability provided by the 1-carbacephalosporin over the cephalosporin nucleus,' we focused on 3-substituents which exploited this stability difference. Access to l-carbacephem-3-enol triflate ( la)233 prompted methods of development for conversion to the 3-vinyl (21, 3-(substituted)-alkyl(2), and 3-ester (4) analogues. Numerous reports, especially from Stille's group, have demonstrated the utility of the palladium-catalyzed coupling of vinyl halides and triflates with organo~tannanes.~ Unfortunately, there 'This paper is dedicated to the memory of the late Professor J. K. Stille.
Methotrexate is an efficacious immunosuppressant for induction and maintenance of remission in Crohn's disease. The goal of this pilot study was to determine whether total or individual methotrexate glutamate levels (MTXGlu ) in red blood cells correlate with disease activity and adverse events in Crohn's disease. A cross-sectional study was undertaken with 12 patients on a stable dose of 25 mg weekly methotrexate (oral or subcutaneous). Clinical disease activity was assessed by the Harvey-Bradshaw Index (HBI), and biologic disease activity was measured by inflammatory markers. Concentrations of individual MTXGlu levels were measured in red blood cells (RBCs) using high-performance liquid chromatography-mass spectrometry. No association was observed between RBC individual (MTXGlu ) or total methotrexate glutamate concentrations and clinical disease activity (HBI score) or inflammatory markers or adverse events. Although Crohn's disease patients in remission appeared to generally have higher RBC total longer-chain methotrexate polyglutamate (MTXGlu ) concentrations compared with those with active disease, a definitive association between RBC MTXGlu levels and clinical disease activity could not be established. Larger longitudinal studies in patients with diverse disease activity are needed to establish the value of MTXGlu levels as indicators of treatment efficacy and clinical outcome.
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