Aspergillus pleural empyema is a rare but often fatal infection complicating thoracic surgery. Three men and one woman aged 23-47 years were diagnosed with Aspergillus pleural empyema after lung resection. Underlying diseases were lung cancer (n = 2), Hodgkin's disease (n = 1) and thoracic trauma (n = 1). The treatment protocol consisted of systemic anti-fungal treatment with caspofungin and voriconazole, intrapleural application of amphotericin B and surgical debridement with secondary closure of the leaking bronchial stump. Two patients with chronic Aspergillus pleural empyema had been pretreated with itraconazole and/or amphotericin B. Two patients were treated with a thoracostoma. Two patients had undergone pneumonectomy for previously diagnosed pulmonary aspergillosis. Caspofungin was given for 13-60 days, Voriconazole for up to 100 days. Surgical debridement was performed in all cases and in two cases the created thoracostoma was closed during a second surgical procedure. Aspergillus PCR using blood samples, bronchoalveolar lavage or aspiration fluid was used for monitoring. All four patients had complete clinical and microbiological remission. Our case series shows promising results and underscores the importance of a combined therapeutic approach for Aspergillus pleural empyema consisting of anti-fungal treatment and surgery. Voriconazole and caspofungin seem to be a suitable combination for this infection.

Functional tumor-specific cytotoxic T cells elicited by therapeutic cancer vaccination in combination with oncolytic viruses offer opportunities to address resistance to checkpoint blockade therapy. Two cancer vaccines, the self-adjuvanting protein vaccine KISIMA, and the recombinant oncolytic vesicular stomatitis virus pseudotyped with LCMV-GP expressing tumor-associated antigens, termed VSV-GP-TAA, both show promise as a single agent. Here we find that, when given in a heterologous prime-boost regimen with an optimized schedule and route of administration, combining KISIMA and VSV-GP-TAA vaccinations induces better cancer immunity than individually. Using several mouse tumor models with varying degrees of susceptibility for viral replication, we find that priming with KISIMA-TAA followed by VSV-GP-TAA boost causes profound changes in the tumor microenvironment, and induces a large pool of poly-functional and persistent antigen-specific cytotoxic T cells in the periphery. Combining this heterologous vaccination with checkpoint blockade further improves therapeutic efficacy with long-term survival in the spectrum. Overall, heterologous vaccination with KISIMA and VSV-GP-TAA could sensitize non-inflamed tumors to checkpoint blockade therapy.

The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment.

Group Milleri streptococci (GMS), a heterogeneous group of streptococci, are associated with purulent infections. This study was a retrospective analysis of all consecutive thoracic infections of GMS between 2001 and 2004. Of 246 surgical GMS infections, thoracic infections accounted for 4.5 per cent, including 10 pleural infections (eight empyemas and two infected pleural effusions) and one mediastinal infection. The etiology of pleural infection was parapneumonic (7), second to esophageal perforation (1), liver transplantation (1), and liver resection (1). Polymicrobial infections were present in 64 per cent. All patients underwent removal of the infected masses, including drainage (3), thoracoscopic decortication (5), thoracotomy with debridement (2), and incision with drainage (1). The case fatality rate was 9 per cent (there was one patient with congestive heart disease unfit to undergo surgical empyema evacuation) and the recurrence rate was 27.3 per cent (three patients). Combined antibiotic/surgical treatment was successful in all other cases. GMS isolates were susceptible to clindamycin and all β-lactam antibiotics except ceftazidime, but were resistant to aminoglycosides. If found intrathoracically, GMS frequently progress to severe empyema. Therefore, timely removal of pleural collection by percutaneous drainage or surgical intervention seems indicated. If surgery is required, thoracoscopic decortication may be the preferred approach.