Leukocytoclastic Vasculitis in an Adolescent with New-Onset Crohn's Disease.

Extraintestinal manifestations frequently affect patients with inflammatory bowel disease. They can involve virtually any organ, with the musculoskeletal and integumentary systems being the most common. Leukocytoclastic vasculitis is a rare extraintestinal manifestation of inflammatory bowel disease, especially at disease onset. It has been reported to occur in association with Crohn's disease and trimethoprim/sulfamethoxazole (TMP-SMX) exposure independently. We report a case of a 14-year-old female who developed leukocytoclastic vasculitis after exposure to TMP-SMX and was ultimately diagnosed with Crohn's disease. The patient presented with purpura, oral ulcers, abdominal pain, and intermittent bloody stools. Colonoscopy showed colonic inflammation, and biopsies revealed severe chronic active colitis with crypt abscesses. A skin biopsy confirmed the diagnosis of leukocytoclastic vasculitis. Management consisted of high-dose steroids and infliximab, with resolutions of her symptoms. This case emphasizes that extraintestinal manifestations are multifactorial in nature, with the example of an existing genetic predisposition through Crohn's disease and a triggering factor such as TMP-SMX.

Infective intracardiac lesion in the setting of Mycobacterium franklinii bacteremia identified by cell-free DNA sequencing in a child with acute lymphoblastic leukemia: A potential new foe in intracardiac infections.

Mycobacterium franklinii (Mfra) is a recently identified member of the Mycobacterium chelonae-abscessus complex (MCAC), a rapidly growing, acid-fast bacilli that have the potential to cause invasive human infections. Identification of Mfra is crucial for selecting the appropriate antimicrobial therapy, as Mfra displays a unique susceptibility profile compared to other MCAC members. The literature on Mfra is limited, with a few studies focusing on respiratory and skin infections. To our knowledge, we describe the first reported case of cardiac involvement associated with Mfra bacteremia in a patient with acute lymphoblastic leukemia. The isolation of Mfra through a next-generation sequencing test allowed for prompt identification and subsequent implementation of tailored antimicrobial agents, ultimately resulting in positive clinical outcomes. This case also emphasizes the significance of next-generation testing in managing immunocompromised patients with persistent fever.

An artificial self-sufficient cytochrome P450 directly nitrates fluorinated tryptophan analogs with a different regio-selectivity.

Aromatic nitration is an immensely important industrial process to produce chemicals for a variety of applications, but it often suffers from multiple unsolved challenges. Enzymes as biocatalysts have been increasingly used for organic chemistry synthesis due to their high selectivity and environmental friendliness, but nitration has benefited minimally from the development of biocatalysis. In this work, we aimed to develop TxtE as practical biocatalysts for aromatic nitration. TxtE is a unique class I cytochrome P450 enzyme that nitrates the indole of l-tryptophan. To develop cost-efficient nitration processes, we fused TxtE with the reductase domains of CYP102A1 (P450BM3) and of P450RhF to create class III self-sufficient biocatalysts. The best engineered fusion protein was comparable with wild type TxtE in terms of nitration performance and other key biochemical properties. To demonstrate the application potential of the fusion enzyme, we nitrated 4-F-dl-tryptophan and 5-F-l-tryptophan in large scale enzymatic reactions. Tandem MS/MS and NMR analyses of isolated products revealed altered nitration sites. To our knowledge, these studies represent the first practice in developing biological nitration approaches and lay a solid basis to the use of TxtE-based biocatalysts for the production of valuable nitroaromatics.