Osteomyelitis of the rib cage by Aspergillus flavus

BackgroundAspergillus osteomyelitis of the ribs is relatively uncommon. It is a debilitating and severe form of invasive aspergillosis.Case reportA 61year-old female presented with spontaneous chest pain on the right side of the rib cage and a palpable soft-tissue mass. FDG-PET/CT scan identified activity in the infected site. The lesion was punctured, and purulent material was sent to the laboratory. Aspergillus complex Flavi was isolated. An antifungal treatment with voriconazole was started. The lesion healed, and no recurrence was observed at 8-month follow-up. Molecular identification of the isolate was based on PCR amplification and sequencing of β-tubulin gene. Aspergillus flavus was identified.ConclusionsOur case highlights the relevance of microbiological studies in patients with osteomyelitis and the involvement of soft tissue. The FDG-PET/CT scan was found to be a useful tool for revealing the extent of the disease and evaluating the response to the antifungal therapy.     

Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma,follicular lymphoma,or Richter's transformation

We analyzed potential biomarkers of response to ibrutinib plus nivolumab in biopsies from patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Richter''s transformation (RT) from the LYM1002 phase I/IIa study, using programmed death ligand 1 (PD-L1) immunohistochemistry, whole exome sequencing (WES), and gene expression profiling (GEP). In DLBCL, PD-L1 elevation was more frequent in responders versus nonresponders (5/8 [62.5%] vs. 3/16 [18.8%]; p = 0.065; complete response 37.5% vs. 0%; p = 0.028). Overall response rates for patients with WES and GEP data, respectively, were: DLBCL (38.5% and 29.6%); FL (46.2% and 43.5%); RT (76.5% and 81.3%). In DLBCL, WES analyses demonstrated that mutations in RNF213 (40.0% vs. 6.2%; p = 0.055), KLHL14 (30.0% vs. 0%; p = 0.046), and LRP1B (30.0% vs. 6.2%; p = 0.264) were more frequent in responders. No responders had mutations in EBF1, ADAMTS20, AKAP9, TP53, MYD88, or TNFRSF14, while the frequency of these mutations in nonresponders ranged from 12.5% to 18.8%. In FL and RT, genes with different mutation frequencies in responders versus nonresponders were: BCL2 (75.0% vs. 28.6%; p = 0.047) and ROS1 (0% vs. 50.0%; p = 0.044), respectively. Per GEP, the most upregulated genes in responders were LEF1 and BTLA (overall), and CRTAM (germinal center B-cell–like DLBCL). Enriched pathways were related to immune activation in responders and resistance-associated proliferation/replication in nonresponders. This preliminary work may help to generate hypotheses regarding genetically defined subsets of DLBCL, FL, and RT patients most likely to benefit from ibrutinib plus nivolumab.     

Transcriptional programming drives Ibrutinib-resistance evolution in mantle cell lymphoma

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