Radical treatment for blastomycosis following unsuccessful liposomal amphotericin.

Pulmonary blastomycosis is a respiratory disease that is caused by the fungus Blastomyces spp, which is acquired through inhalation of the fungal spores. Blastomycosis is relatively uncommon, with yearly incidence rate of 1-2 cases per 100 000 people. Blastomycosis is a disease that is endemic to the midwest and southern regions of the USA, most commonly affecting immunocompromised patients. About 50% of patients are asymptomatic, but for those who progress to acute respiratory distress syndrome (ARDS) mortality can be as high as 80%. Patients with severe blastomycosis are initially treated with intravenous amphotericin B, followed by long-term itraconazole maintenance therapy. In this Grand Round, we present the case of an immunocompetent 35-year-old man diagnosed with chronic pulmonary blastomycosis who had a poor response to 10 days of intravenous liposomal amphotericin B (L-AmB). He was endotracheally intubated and eventually cannulated for extracorporeal membrane oxygenation (ECMO), due to worsening respiratory function. L-AmB was replaced with a continuous infusion of intravenous amphotericin B deoxycholate (AmB-d). He improved significantly and was decannulated from ECMO on day 9 of AmBd continuous infusion and extubated on day 12 Although L-AmB is considered first-line treatment for blastomycosis, mortality remains high for patients with ARDS associated with blastomycosis. This case highlights the importance of considering AmB-d continuous infusions for patients with severe blastomycosis who might have poor clinical responses to L-AmB.

Prospective evaluation of fluciclovine (18F) PET-CT and MRI in detection of recurrent prostate cancer in non-prostatectomy patients.

PURPOSE: To investigate the disease detection rate, diagnostic performance and interobserver agreement of fluciclovine (18F) PET-CT and multiparametric magnetic resonance imaging (mpMR) in recurrent prostate cancer. METHODS: Twenty-four patients with biochemical failure after non-prostatectomy definitive therapy, 16/24 of whom had undergone brachytherapy, underwent fluciclovine PET-CT and mpMR with interpretation by expert readers blinded to patient history, PSA and other imaging results. Reference standard was established via a multidisciplinary truth panel utilizing histology and clinical follow-up (22.9 ±â€¯10.5 months) and emphasizing biochemical control. The truth panel was blinded to investigative imaging results. Diagnostic performance and interobserver agreement (kappa) for the prostate and extraprostatic regions were calculated for each of 2 readers for PET-CT (P1 and P2) and 2 different readers for mpMR (M1 and M2). RESULTS: On a whole body basis, the detection rate for fluciclovine PET-CT was 94.7% (both readers), while it ranged from 31.6-36.8% for mpMR. Kappa for fluciclovine PET-CT was 0.90 in the prostate and 1.0 in the extraprostatic regions. For mpMR, kappa was 0.25 and 0.74, respectively. In the prostate, 22/24 patients met the reference standard with 13 malignant and 9 benign results. Sensitivity, specificity and positive predictive value (PPV) were 100.0%, 11.1% and 61.9%, respectively for both PET readers. For mpMR readers, values ranged from 15.4-38.5% for sensitivity, 55.6-77.8% for specificity and 50.0-55.6% for PPV. For extraprostatic disease determination, 18/24 patients met the reference standard. Sensitivity, specificity and PPV were 87.5%, 90.0% and 87.5%, respectively, for fluciclovine PET-CT, while for mpMR, sensitivity ranged from 50 to 75%, specificity 70-80% and PPV 57-75%. CONCLUSION: The disease detection rate for fluciclovine PET-CT in non-prostatectomy patients with biochemical failure was 94.7% versus 31.6-36.8% for mpMR. For extraprostatic disease detection, fluciclovine PET-CT had overall better diagnostic performance than mpMR. For the treated prostate, fluciclovine PET-CT had high sensitivity though low specificity for disease detection, while mpMR had higher specificity, though low sensitivity. Interobserver agreement was also higher with fluciclovine PET-CT compared with mpMR.

Diagnostic Utility of PD-L1 Expression in Lung Adenocarcinoma: Immunohistochemistry and RNA In Situ Hybridization.

BACKGROUND: Programmed death receptor and programmed death ligand (PD-L1) are immunoregulatory proteins. Nonsmall cell lung cancer bypasses the immune system through the induction of protumorigenic immunosuppressive changes. The better understanding of immunology and antitumor immune responses has brought the promising development of novel immunotherapy agents like programmed death receptor checkpoint inhibitors. The aim of this study was to investigate the expression of PD-L1 in lung adenocarcinoma (ADC), comparing 2 different technologies: immunohistochemistry (IHC) by 2 methods versus RNA in situ hybridization (RISH). METHODOLOGY: In total, 20 cases of ADC of the lung and 4 samples of metastatic colon ADC were selected. Evaluation of PD-L1 expression was performed by IHC and RISH. RISH was performed using RNAscope. Both methods were scored in tumor cells and quantified using combined intensity and proportion scores. RESULTS: Eight of 20 (40%) lung ADC and 2 of 4 (50%) colon ADC were positive for PD-L1 with Cell Signaling IHC, and 65% lung ADC were positive by Dako IHC (13/20). All 4 cases of colon ADC were negative. When evaluated by RISH, 12 lung ADC (60%) and 1 colon ADC (25%) were PD-L1 positive. CONCLUSIONS: RNAscope probes provide sensitive and specific detection of PD-L1 in lung ADC. Both IHC methods (Cell Signaling and Dako) show PD-L1 expression, with the Dako method more sensitive (40% vs. 65%). This study illustrates the utility of RISH and Cell Signaling IHC as complementary diagnostic tests, and Food and Drug Administration approved Dako IHC as a companion diagnostic test.