Tissue plasminogen activator with prolonged dwell time effectively evacuates pleural effusions.

OBJECTIVES: Fibrinolytic therapy can be effective for management of complex pleural effusions. Tissue plasminogen activator (tPA, 10 mg) and deoxyribonuclease (DNAse) every 12 h with a dwell time of one hour is a common strategy based on published data. We used a simpler protocol of tPA (4 mg) without DNAse but with a longer dwell time of 12 h, repeated daily. We reviewed our results. METHODS: Charts were reviewed and demographics, clinical data and treatment information were abstracted. Outcomes were assessed based on radiographic findings and need for surgery. RESULTS: Two hundred and fifteen effusions in 207 patients (8 bilateral) were identified. 85% were either infectious or malignant. Two hundred and forty nine chest tubes were used: 84% were 10 Fr or 12 Fr and 7% were PleurX®. Five hundred and thirty one doses of tPA were given. The median number of doses per effusion was 2 (range 1-10), and 84% of effusions were treated with three or fewer doses. There were no significant bleeding complications. Median time to chest tube removal was 6 days (range 1 to 98, IQR 4 to 10). Drainage was considered complete for 78% of effusions, while 6% required decortication. CONCLUSIONS: Low dose tPA daily with a 12 h dwell time may be as effective as the standard regimen of tPA and DNAse twice daily with one hour dwell. For most patients only three doses were required, and small pigtail catheters were sufficient. This regimen uses less medication and is logistically much easier than the current standard.

The Associations between Racial Disparities, Health Insurance, and the Use of Amputation as Treatment for Malignant Primary Bone Neoplasms in the US: A Retrospective Analysis from 1998 to 2016.

Primary bone neoplasms (PBNs) represent less than 1% of diagnosed cancers each year. Significant treatment disparities exist between racial and ethnic groups. We investigated patients with PBNs to determine an association between race/ethnicity and procedure-type selection. A non-concurrent cohort study was conducted using the SEER database. Patients diagnosed with PBNs between 1998 and 2016 were included (n = 5091). Patients were classified into three racial groups (Black, White and Asian Pacific Islanders) and were assessed by procedure-type received. The outcome was amputation. Race was not associated with increased amputation incidence. Hispanic patients had a 40% increased likelihood of amputation (OR 1.4; 95% CI 1.2-1.6). Insurance status was an independent predictor of procedure selection. Uninsured patients were 70% more likely to receive amputation than insured patients (OR 1.7; 95% CI 1.1-2.8). We recommend provider awareness of patients less likely to seek regular healthcare in the context of PBNs.

Nucleoporin-93 reveals a common feature of aggressive breast cancers: robust nucleocytoplasmic transport of transcription factors.

By establishing multi-omics pipelines, we uncover overexpression and gene copy-number alterations of nucleoporin-93 (NUP93), a nuclear pore component, in aggressive human mammary tumors. NUP93 overexpression enhances transendothelial migration and matrix invasion in vitro, along with tumor growth and metastasis in animal models. These findings are supported by analyses of two sets of naturally occurring mutations: rare oncogenic mutations and inactivating familial nephrotic syndrome mutations. Mechanistically, NUP93 binds with importins, boosts nuclear transport of importins' cargoes, such as ß-catenin, and activates MYC. Likewise, NUP93 overexpression enhances the ultimate nuclear transport step shared by additional signaling pathways, including TGF-ß/SMAD and EGF/ERK. The emerging addiction to nuclear transport exposes vulnerabilities of NUP93-overexpressing tumors. Congruently, myristoylated peptides corresponding to the nuclear translocation signals of SMAD and ERK can inhibit tumor growth and metastasis. Our study sheds light on an emerging hallmark of advanced tumors, which derive benefit from robust nucleocytoplasmic transport.