Serum TPS (cytokeratin-18) is elevated in patients with non-malignant liver diseases, particularly in those with prominent cytolysis. Further studies are needed to evaluate the use of TPS as a marker of liver disease.
Background: Second-line treatment of KRAS-mutated metastatic colorectal cancer (mCRC) confers a dismal patient (pt) outcome with response rates of 4% to FOLFIRI (5-fluorouracil (5FU), leucovorin, irinotecan) + bevacizumab (bev) and median progression-free survival (PFS) of 5.5 months. PLK1 is a serine/threonine kinase, master regulator of mitosis. PLK1 inhibition has synthetic lethality with KRAS-mutated CRC tumor cells. Onvansertib is an oral and highly-selective PLK1 inhibitor with demonstrated efficacy as a single agent and synergistically with irinotecan in CRC preclinical models.Methods: This single-arm phase Ib/II study (NCT03829410) assesses the safety and preliminary efficacy of onvansertib in combination with FOLFIRI + bev in second line KRAS-mutated mCRC. Pts are treated with onvansertib (days 1-5) + FOLFIRI-bev (day 1) in a 14-day cycle. In the phase Ib, a standard 3 + 3 dose-escalation design is used to determine the maximum tolerated dose or recommended phase II dose. Secondary objectives are preliminary efficacy determined by radiographic scans every 8 weeks and reduction in KRAS mutant allelic burden evaluated by liquid biopsy.
Fournier's gangrene is a form of necrotizing fasciitis of the perineal region that frequently affects immunocompromised patients. In most cases the point of entry of the infecting microorganisms goes undetected. A case of necrotizing fasciitis was diagnosed in a 77-year-old male with diabetes mellitus following an injection of botulinum toxin in the anal sphincter to treat an anal fissure.
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