Risk factors for infection and acute urinary retention following transperineal prostate biopsy.

PURPOSE: To calculate the frequency of infection and acute urinary retention (AUR) following transperineal (TP) prostate biopsy at a single high-volume academic institution and determine risk factors for developing these post-biopsy conditions. METHODS: Men undergoing TP prostate biopsy from 2012 to 2022 at our institution were retrospectively identified and chart reviewed. TP biopsies were performed with TR ultrasound (TRUS) guidance with anesthesia using a brachytherapy grid template. TRUS volumes were recorded during the procedure, and magnetic resonance imaging (MRI) volumes were calculated using the ellipsoid formula. When available, MRI volume was used for all analysis, and when absent, TRUS volume was used. AUR was defined as requiring urinary catheter placement within 72 h post-biopsy for inability to urinate. Univariable analysis was performed and variables with p < 0.1 and/or established clinical relevance were included in a backward binary logistic regression to produce an optimized model that fit the data without collinearity between variables. RESULTS: A total of 767 TP biopsies were completed in the study window. The frequency of infection was 1.83% (N = 14/767). The total frequency of AUR was 5.48% (N = 42/767). On multivariable regression, patients who went into AUR were five times as likely to develop infection (p = 0.020). Patients with infection post-TP biopsy were four times as likely to develop AUR (p = 0.047) and with prostates > 61.21 cc were three times as likely (p = 0.019). CONCLUSION: According to our model, AUR is the greatest risk factor for infection post-TP biopsy. With regard to AUR risks, infection post-biopsy and prostate size > 61.21 cc are the greatest risk factors.

Extracorporeal Membrane Oxygenation During Surgical Stabilization of Rib Fractures in Successful Management of Severe Blunt Chest Trauma.

Early surgical stabilization of rib fracture (SSRF) improves outcomes in patients with flail physiology and severely displaced fractures. We present two cases of patients with severe chest injury and large flail segment who underwent SSRF while on veno-venous extracorporeal membrane oxygenation (VV-ECMO). The patients developed respiratory failure within 24 hours of admission requiring VV-ECMO. The extent of their chest wall injury limited pulmonary mechanics prohibiting transition off VV-ECMO. Therefore, SSRF was performed on hospital days 2 and 3 and while on VV-ECMO support. Stabilizing the chest wall allowed for improved ventilation and successful decannulation from VV-ECMO on postoperative days 3 and 4. Ultimately, both achieved a functional recovery and were discharged home. These cases demonstrate a unique thoracic damage control strategy wherein SSRF is performed while on VV-ECMO. Improving chest stability and pulmonary mechanics with SSRF allowed for safe transition off VV-ECMO and achieved a favorable long-term outcome.

Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma.

Astatine-211-parthanatine ([211At]PTT) is an alpha-emitting radiopharmaceutical therapeutic that targets poly(adenosine-diphosphate-ribose) polymerase 1 (PARP1) in cancer cells. High-risk neuroblastomas exhibit among the highest PARP1 expression across solid tumors. In this study, we evaluated the efficacy of [211At]PTT using 11 patient-derived xenograft (PDX) mouse models of high-risk neuroblastoma, and assessed hematological and marrow toxicity in a CB57/BL6 healthy mouse model. We observed broad efficacy in PDX models treated with [211At]PTT at the maximum tolerated dose (MTD 36 MBq/kg/fraction x4) administered as a fractionated regimen. For the MTD, complete tumor response was observed in 81.8% (18 of 22) of tumors and the median event free survival was 72 days with 30% (6/20) of mice showing no measurable tumor >95 days. Reversible hematological and marrow toxicity was observed 72 hours post-treatment at the MTD, however full recovery was evident by 4 weeks post-therapy. These data support clinical development of [211At]PTT for high-risk neuroblastoma.

PARP Targeted Alpha-Particle Therapy Enhances Response to PD-1 Immune-Checkpoint Blockade in a Syngeneic Mouse Model of Glioblastoma.

We have previously demonstrated potent antitumor effects of PARP targeted alpha-therapy with astatine-211-MM4 ([211At]MM4) in neuroblastoma preclinical models, although differential sensitivity suggests it is unlikely to be curative as a single-agent in all tumor types. Alpha-particle induced DNA damage can elicit an immune response that results in T-cell activation against tumor cells; however, tumor cells can evade immune surveillance through expression of programmed death ligand 1 (PD-L1). Therefore, we investigated the effects of α particle therapy in combination with immune-checkpoint blockade using astatine-211-MM4 and anti-programmed death receptor 1 (anti-PD-1) immunotherapy in a syngeneic mouse model of glioblastoma. We characterized the sensitivity of four human glioblastoma cell lines to [211At]MM4 in vitro. To evaluate [211At]MM4 treatment effects on hematological tissues, complete blood counts were performed after a single dose at 12, 24, or 36 MBq/kg. In vivo efficacy was evaluated in a syngeneic mouse model of glioblastoma using GL26 glioblastoma cells in CB57BL/6J mice treated with either 36 MBq/kg [211At]MM4, anti-PD-1 antibody, or a combination of the two. Following a single dose of [211At]MM4, lymphocytes are significantly decreased compared to control at both 72 h and 1 week following treatment followed by recovery of counts by 2 weeks. However, neutrophils showed an increase with all dose levels of [211At]MM4 exhibiting higher levels than control. The average best tumor responses for combination, anti-PD-1, and [211At]MM4 were 100%, 83.6%, and 58.2% decrease in tumor volume, respectively. Average progression free intervals for combination, anti-PD-1, [211At]MM4, and control groups was 65, 36.4, 23.2, and 3 days, respectively. The percentages of disease-free mice at the end of the study for combination and anti-PD-1 were 100% and 60%, while [211At]MM4 and control groups were both 0%. In summary, combination therapy was more effective than either single agent in all response categories analyzed, highlighting the potential for PARP targeted alpha-therapy to enhance PD-1 immune-checkpoint blockade.