CD8 T cell response and its released cytokine IFN-γ are necessary for lung alveolar epithelial repair during bacterial pneumonia.

Introduction: Alveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-γ, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown. Methods: We used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by Streptococcus pneumoniae. To determine whether CD8 T cells and their released cytokine IFN-γ are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-γ monoclonal antibody (mAb) treatment in vivo. We assessed the effects of CD8 T cells and cytokine IFN-γ on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system in vitro. Results: We detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by Streptococcus pneumoniae. Depletion of CD8 T cells or neutralization of cytokine IFN-γ using anti-CD8 or anti-IFN-γ monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-γ with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-γ signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system. Discussion: Our data demonstrate that CD8 T-cell response and cytokine IFN-γ are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia.

Symptomatic Improvement of Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: A Comparative Systematic Review and Meta-Analysis of 4 Different Minimally Invasive Therapies.

PURPOSE: To review and compare the outcomes of prostatic artery embolization (PAE) with 3 other minimally invasive surgical treatments for benign prostatic hyperplasia, including photoselective vaporization (PVP), prostatic urethral lift (PUL), and water vapor thermal therapy (WV). METHODS: A literature review was used to identify 35 publications, which included 2,653 patients (studies, patients): PVP (13, 949), PUL (9, 577), WV (3, 330), and PAE (10, 728). The international prostate symptom score (IPSS) and the international index of erectile function (IIEF-5) and quality of life (QOL) scores were recorded at baseline, 6 months, and 12 months. Meta-analyses, pooling the standardized mean difference between scores recorded before and after treatment, were conducted for each modality and time point to assess the magnitude of a therapy's effect to yield pooled effect sizes. A negative score indicates IPSS and QOL improvement. A positive score indicates IIEF-5 improvement. RESULTS: At 6 and 12 months, the IPSS and QOL were most improved after PVP, followed by that after PAE, PUL, and, lastly, WV (measured only at 12 months). Between 6 and 12 months, the IPSS and QOL improved with PAE and worsened with PVP and PUL. Only PAE demonstrated statistical improvement in the IIEF-5, which improved from 6 to 12 months. CONCLUSIONS: PVP and PAE resulted in the largest improvements in the IPSS and QOL. Only PAE resulted in improvement of the IIEF-5.

Comparative Effectiveness and Tolerability of Transperineal MRI-Targeted Prostate Biopsy under Local versus Sedation.

OBJECTIVES: To assess the prostate cancer diagnostic yield, complications, and costs of transperineal prostate biopsies when performed with local anesthesia versus sedation. METHODS: Data were prospectively collected for men undergoing transperineal MRI-targeted biopsy at the outpatient clinic and tertiary hospital of a single center between October 2017 to February 2020. These data included demographic, procedural, and pathologic variables and complications. Time-driven activity-based costing was performed to compare procedural costs. RESULTS: 126 men were included. Age, BMI and PSA were similar for local (n = 45) vs sedation (n = 81), all P>0.05. Detection of clinically significant prostate cancer (CSPC) on combined systematic and targeted biopsy was similar for local vs sedation (24% vs 36%; P = 0.2). Local had lower detection on targeted biopsies alone (8.9% vs 25%; P = 0.03). However, fewer targeted cores were obtained per region of interest with local vs sedation (median 3 vs 4 cores; P<0.01). For local vs sedation, the complication rate was 2.6% and 6.1% (P = 0.6). The median visual analog pain score for local vs sedation was 3/10 vs 0/10 (P<0.01). The mean procedure time for local vs sedation was 22.5 vs 17.5 minutes (48.3 minutes when including anesthesia time). Time-driven activity-based costs for local vs sedation were $961.64 vs $2208.16 (P<0.01). CONCLUSION: Transperineal biopsy with local anesthesia is safe with comparable outcomes to sedation. While the number of cores taken differed, there was no statistical difference in the detection of clinically significant cancer.

VEGF inhibition in urothelial cancer: the past, present and future.

PURPOSE: To describe the role of anti-angiogenic agents that have been used as a treatment approach for locally advanced or metastatic urothelial cancers and to propose future directions. METHODS: PubMed/MEDLINE was searched for articles related to VEGF inhibition and locally advanced or metastatic urothelial cancer. RESULTS: Angiogenesis is a fundamental process for urothelial cancer initiation and progression. First-line therapy for locally advanced or metastatic urothelial cancer includes cisplatin-based chemotherapy combinations; subsequent systemic therapy includes taxanes, nanoparticle albumin-bound (nab) paclitaxel, or pemetrexed. More recently, several anti-PD-L1 and anti-PD-1 antibodies have shown promising activity in the first-line and post-platinum setting; however, immunotherapy remains ineffective in most patients. FGFR inhibitor erdafitinib was recently approved in the third-line setting. Studies on bevacizumab, pazopanib and ramucirumab have shown improved response rates when added to chemotherapy in selected patients, but have not led to overall survival (OS) benefit in randomized controlled studies. CONCLUSION: Anti-angiogenic agents have shown promise in recent studies treating locally advanced or metastatic urothelial cancer. However, further work is needed to elucidate ideal treatment combinations in selected patient populations to maximize benefit, with the ultimate goal of being added to the FDA-approved treatment armamentarium for this disease.

Risk Factors for Infection after Prostate Biopsy in the United States.

METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2001 to 2015 and recorded 30-day infection rates and emergency department, hospital and, intensive care unit (ICU) admissions. We performed adjusted analyses to analyze the effect of age, demographic data, surgeon volume, rectal swab use, and biopsy year on infections. RESULTS: We found that the overall rate of postbiopsy infections increased from 2001 (5.9%) to 2007 (7.2%) but remained stable through 2015. Despite this, postbiopsy emergency room visits rose from 0.2% to 0.5% (95% confidence interval [CI] 0.2%-0.4%, P < .01), hospitalizations rose from 0.5% to 1.3% (95% CI 0.5%-1.0%, P < .01), and ICU admissions increased from 0.1% to 0.3% (95% CI 0.1%-0.3%, P < .01). Patients of surgeons who performed 25 biopsies per year had lower odds of postbiopsy infection (odds ratio 0.65; 95% CI 0.61-0.69) and a lower risk of hospitalization (odds ratio 0.50; 95% CI 0.43-0.59) as compared to patients of surgeons who performed one biopsy per year. Rectal swab use increased over the study period but remained low (1.8% in 2015). CONCLUSION: While the overall rate of postbiopsy infections has stabilized since 2007, admissions to the emergency room, hospital, and ICU continue to rise. Increased surgeon volume was associated with a decreased risk of infection.

To treat or not to treat: Patient exclusion in immune oncology clinical trials due to preexisting autoimmune disease.

Newly developed immune checkpoint inhibitors (ICIs) demonstrate impressive clinical activity. However, they can also cause life-threatening side effects. The efficacy and toxicity associated with ICIs both derive from unregulated, enhanced immune activation. Health care providers have been hesitant to prescribe these medications to patients who have preexisting autoimmune disease (AD) because of concerns that this may exacerbate their underlying immune condition. These patients have also been excluded from ongoing ICI clinical trials. However, new data suggest that the potential benefits of ICI treatment may outweigh the potential risks for this patient group as long as physicians also provide sufficient monitoring for AD exacerbations or other side effects. Therefore, it may be appropriate to include patients with advanced malignancies and preexisting AD in ICI clinical trials when no other effective cancer treatment options exist. Overall, physicians should avoid excluding patients from ICI therapy unnecessarily when the potential benefits outweigh the potential risks.

IDEAL Stage 2a experience with in-office, transperineal MRI/ultrasound software fusion targeted prostate biopsy.

OBJECTIVE: Although the feasibility of transperineal biopsy under local anesthesia has been demonstrated, little is known regarding the application of MRI/ultrasound software fusion targeted biopsy for transperineal biopsy under local anesthesia. The objective of our study is to describe our initial experience with in-office transperineal MRI/ultrasound software fusion targeted biopsy (Idea, Development, Exploration, Assessment, Long-term Follow-up [IDEAL] Stage 2a). METHODS: Between October 2017 and July 2019, 33 men underwent in-office transperineal MRI-targeted biopsy using the Artemis (Eigen, Grass Valley, CA, USA) fixed-robotic arm system. The indication for biopsy was elevated prostate specific antigen (PSA) (n=14), prior negative biopsy (n=10), active surveillance (n=6), and surveillance after partial gland cryoablation (n=3). We prospectively captured patient demographic and clinical characteristics, biopsy outcomes, and complications. Complications were classified according to Common Terminology Criteria for Adverse Events (CTCAE) V.5.0. RESULTS: The median patient age was 67 years (IQR 61-71) and the median serum PSA level was 7.0 ng/mL (IQR 5.1-11.4). The median duration of in-office MRI-targeted transperineal biopsy was 26 min (IQR 23-28). Overall, transperineal MRI-targeted biopsy detected prostate cancer in 18 (54.6%) men, with 8 (24.2%) being clinically significant (Gleason Score ≥3+4, Grade Group ≥2). Clinically significant prostate cancer was detected in four (28.6%) biopsy naïve men, two (20.0%) men with a prior negative, one (16.7%) man on active surveillance and one (33.3%) man following partial gland ablation. Three (9.1%) men experienced complications: two hematuria and one urinary retention. CONCLUSION: Our findings demonstrate the feasibility of the fixed-robotic arm fusion platform for in-office transperineal MRI-targeted biopsy and a low rate of adverse events. However, larger prostate size precludes MRI/ultrasound software fusion and pubic arch interference hindered the transperineal MRI-targeted approach in 9.1% of men. Pubic arch interference was overcome by a free-hand approach with software fusion guidance.