Sheng Yuan Kan

NUT carcinoma is challenging to diagnose and may mimic a germ cell tumor (GCT) due to raised serum alpha-fetoprotein (AFP). A 15-year-old patient presented with back pain and cough. Investigation revealed a mediastinal mass and multiple bone metastases. Serum AFP was highly elevated, consistent with a metastatic malignant nonseminomatous GCT. Aggressive chemotherapy was initiated with initial response, unfortunately not sustained. Diagnostic biopsy showed undifferentiated tumor cells with weak GCT immunophenotype but was ultimately non-diagnostic. Serum miR-371a-3p levels, highly sensitive/specific for malignant GCTs, were negative casting diagnostic suspicion. Routine use of agnostic molecular investigations, including whole genome sequencing, identified a chromosome 15:19 translocation, with BRD4::NUTM1 gene fusion on RNA sequencing, confirming NUT carcinoma. Subsequent NUTM1 immunohistochemistry was positive. A high index of clinical suspicion is required for non-pathologically/molecularly confirmed diagnoses. Serum miR-371a-3p quantification ruled out malignant GCT and routine agnostic molecular studies identified the correct diagnosis; a low threshold for NUTM1 immunohistochemistry is thus recommended.

Nanofibers of the poorly water-soluble antibiotic ciprofloxacin (CIP) were fabricated in the form of an amorphous solid dispersion by using poly(vinyl pyrrolidone) as a polymer matrix, by the low-cost electrospinning method. The solubility of the nanofibers as well as their in vitro diffusion were remarkably higher than those of the CIP powder or the physical mixture of the two components. The fiber size and morphology were optimized, and it was found that the addition of the CIP to the electrospinning solution decreased the nanofiber diameter, leading to an increased specific surface area. Structural characterization confirmed the interactions between the drug and the polymer and the amorphous state of CIP inside the nanofibers. Since the solubility of CIP is pH-dependent, the in vitro solubility and dissolution studies were executed at different pH levels. The nanofiber sample with the finest morphology demonstrated a significant increase in solubility both in water and pH 7.4 buffer. Single medium and two-stage biorelevant dissolution studies were performed, and the release mechanism was described by mathematical models. Besides, in vitro diffusion from pH 6.8 to pH 7.4 notably increased when compared with the pure drug and physical mixture. Ciprofloxacin-loaded poly(vinyl pyrrolidone) (PVP) nanofibers can be considered as fast-dissolving formulations with improved physicochemical properties.