A meta-analysis for the role of aminoglycosides and tigecyclines in combined regimens against colistin- and carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

We aimed to describe the effect of aminoglycosides and tigecycline to reduce the mortality in colistin- and carbapenem-resistant Klebsiella pneumoniae (ColR-CR-Kp) infections. We included the studies with defined outcomes after active or non-active antibiotic treatment of ColR-CR-Kp infections. The active treatment was defined as adequate antibiotic use for at least 3 days (72 h) after the diagnosis of ColR-CR-Kp infection by culture. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the checklist of PRISMA 2020 was applied. Crude and adjusted odds ratios (OR) with 95% confidence interval (CI) were calculated and pooled in the random effects model. Adding aminoglycosides to the existing treatment regimen reduced overall mortality significantly (OR 0.34, 95% CI 0.20-0.58). Overall mortality was 34% in patients treated with aminoglycoside-combined regimens and was 60% in patients treated with non-aminoglycoside regimens. Treatment with tigecycline is not found to reduce mortality (OR: 0.76, 95% CI: 0.47-1.23). Our results suggest that aminoglycoside addition to the existing regimen of colistin- and carbapenem-resistant Klebsiella pneumoniae infections reduces mortality significantly.

Fluorescence-guided extended pelvic lymphadenectomy during robotic radical prostatectomy.

We evaluated and described the impact of prostatic indocyanine green (ICG) injection on extended pelvic lymph node (LN) dissection (ePLND) in robotic-assisted radical prostatectomy (RARP). Between January 2019 and December 2021, we included consecutive 50 PCa patients who underwent ePLND during RARP with (n = 25) or without (n = 25) prostatic ICG injection. ICG injection was performed during abdominal port placement and robot docking. Pelvic LNs reflecting green color were initially excised and then the template was completed. The outcomes of two groups were compared. Overall, nine (36%) and five (20%) of the patients had metastatic LN involvement in the ICG and non-ICG groups, respectively. Of the 509 dissected LNs in the ICG group, 122 (23.9%) were fluorescence active. 20 LNs (3.9%) were metastatic in this group, 9 (45%) of which were ICG+. 408 LNs were resected on the non-ICG group with 8(1.9%) being metastatic. Eight (88.9%) of nine pN+ patients were florescent positive in the ICG group. Out of six patients with pN+ disease, Ga68 PSMA-PET/CT detected positive LNs preoperatively. In addition to preoperative Ga68 PSMA-PET/CT investigation, ICG-guided ePLND might increase identification and removal of metastatic LNs duirng RARP. Improvements in staging and oncologic outcomes may also be seen in intermediate- and high-risk patients.

Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma.

PURPOSE: Extracellular matrix (ECM) component hyaluronan (HA) facilitates malignant phenotypes of glioblastoma (GBM), however, whether HA impacts response to GBM immunotherapies is not known. Herein, we investigated whether degradation of HA enhances oncolytic virus immunotherapy for GBM. EXPERIMENTAL DESIGN: Presence of HA was examined in patient and murine GBM. Hyaluronidase-expressing oncolytic adenovirus, ICOVIR17, and its parental virus, ICOVIR15, without transgene, were tested to determine if they increased animal survival and modulated the immune tumor microenvironment (TME) in orthotopic GBM. HA regulation of NF-κB signaling was examined in virus-infected murine macrophages. We combined ICOVIR17 with PD-1 checkpoint blockade and assessed efficacy and determined mechanistic contributions of tumor-infiltrating myeloid and T cells. RESULTS: Treatment of murine orthotopic GBM with ICOVIR17 increased tumor-infiltrating CD8+ T cells and macrophages, and upregulated PD-L1 on GBM cells and macrophages, leading to prolonged animal survival, compared with control virus ICOVIR15. High molecular weight HA inhibits adenovirus-induced NF-κB signaling in macrophages in vitro, linking HA degradation to macrophage activation. Combining ICOVIR17 with anti-PD-1 antibody further extended the survival of GBM-bearing mice, achieving long-term remission in some animals. Mechanistically, CD4+ T cells, CD8+ T cells, and macrophages all contributed to the combination therapy that induced tumor-associated proinflammatory macrophages and tumor-specific T-cell cytotoxicity locally and systemically. CONCLUSIONS: Our studies are the first to show that immune modulatory ICOVIR17 has a dual role of mediating degradation of HA within GBM ECM and subsequently modifying the immune landscape of the TME, and offers a mechanistic combination immunotherapy with PD-L1/PD-1 blockade that remodels innate and adaptive immune cells.