Catheter-directed thrombolysis guided by pulmonary artery pressure registration in pulmonary embolism: a case report.

Background: Duration and dosage of thrombolysis for ultrasound-assisted catheter-directed thrombolysis (UACDT) in patients with intermediate high-risk pulmonary embolism remain controversial and treatment protocols vary. Case summary: A 58-year-old female patient suffered from a right-sided urolithiasis. The clinical course was complicated by an intermediate high-risk pulmonary embolism [pulmonary embolism severity index (PESI) score 108 points and simplified PESI ≥1] with bilateral proximal thrombus and significant right heart dysfunction. The pulmonary embolism response team (PERT) made a decision towards UACDT. The standard duration of UACDT ranges between 6 and 15 h depending on clinical parameters. In this particular case, the clinical parameters such as heart rate (no tachycardia) or oxygen saturation (chronic obstructive pulmonary disease) might lead to premature termination of UACDT. Therefore, PERT decided to additionally monitor pulmonary artery pressure (PAP) continuously during the UACDT via a separate pigtail catheter in the pulmonary artery. Ultrasound-assisted catheter-directed thrombolysis was performed using 1 mg/h recombinant tissue plasminogen activator (rtPA) per catheter, while PAP was registered continuously. Heart rate and oxygen saturation remained unchanged during UACDT. However, after 6 h of UACDT, systolic PAP decreased slightly from 62 to 55 mmHg and therapy was prolonged to 15 h. Pulmonary artery pressure dropped to 46 mmHg after 15 h. The patient was discharged from hospital at Day 7, and echocardiography revealed no signs of right heart dysfunction. Discussion: Dosage of the thrombolysis agent and duration of UACDT are still a matter of debate. Besides clinical parameters and transthoracic echocardiography, invasive real-time PAP monitoring during UACDT could facilitate important information for therapy guidance in selected cases.

Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies.

BACKGROUND: Predicting metastasis in melanoma patients is important for disease management and could help to identify those who might benefit from adjuvant treatment. The aim of this study was to investigate whether the tumor microenvironment-derived protein S100A8/A9 qualifies as prognostic marker for melanoma patients, also in the setting of immunotherapy. METHODS: S100A8/A9 gene and protein expression were analyzed on melanocytic nevi, primary melanomas and metastases using a cDNA library and three independent tissue-microarrays (TMA). Serum levels of S100A8/A9 were measured using a specific ELISA in two independent cohorts of 354 stage III and stage IV melanoma patients as well as in two independent cohorts of patients treated with the PD-1 antibody pembrolizumab. RESULTS: cDNA analysis revealed an upregulation of S100A8 and S100A9 gene expression in melanoma metastases compared to primary melanomas. Significantly higher numbers of infiltrating S100A8/A9 positive cells were found in tissue samples of metastasizing primary melanomas compared to non-metastasizing melanomas (P < .0001) and in melanomas of short-term survivors compared to long-term survivors (P < .0001). Serum S100A8/A9 levels > 5.5 mg/l were associated with impaired overall survival in two independent cohorts (both P < .0001). Importantly, patients with serum elevated S100A8/A9 treated with pembrolizumab showed significantly impaired survival compared to patients with lower S100A8/A9 levels (cohort 1: P = .0051; cohort 2: P < .0001). CONCLUSIONS: The tumor microenvironment-associated protein S100A8/A9 serves as a novel prognostic marker for metastasis and survival of metastatic melanoma patients and predicts response to immunotherapy with pembrolizumab. These data underscore the significance of tumor microenvironment-derived factors as suitable biomarkers for melanoma.