Neonates are highly susceptible to intracellular pathogens, leading to high morbidity and mortality rates. CD8
T lymphocytes are responsible for the elimination of infected cells. Understanding the ...response of these cells to normal and high stimulatory conditions is important to propose better treatments and vaccine formulations for neonates. We have previously shown that human neonatal CD8
T cells overexpress innate inflammatory genes and have a low expression of cytotoxic and cell signaling genes. To investigate the activation potential of these cells, we evaluated the transcriptome of human neonatal and adult naïve CD8
T cells after TCR/CD28 signals ± IL-12. We found that in neonatal cells, IL-12 signals contribute to the adult-like expression of genes associated with cell-signaling, T-cell cytokines, metabolism, and cell division. Additionally, IL-12 signals contributed to the downregulation of the neutrophil signature transcription factor CEBPE and other immaturity related genes. To validate the transcriptome results, we evaluated the expression of a series of genes by RT-qPCR and the promoter methylation status on independent samples. We found that in agreement with the transcriptome, IL-12 signals contributed to the chromatin closure of neutrophil-like genes and the opening of cytotoxicity genes, suggesting that IL-12 signals contribute to the epigenetic reprogramming of neonatal lymphocytes. Furthermore, high expression of some inflammatory genes was observed in naïve and stimulated neonatal cells, in agreement with the high inflammatory profile of neonates to infections. Altogether our results point to an important contribution of IL-12 signals to the reprogramming of the neonatal CD8
T cells.
The presence of positive surgical margins in patients with prostate cancer who underwent robotic-assisted radical prostatectomy is associated with mortality only in patients with adverse clinical and ...pathological characteristics. Particular attention must be paid in case of multifocal positive margins.
Positive surgical margins (PSMs) are frequent in patients undergoing radical prostatectomy (RP). The impact of PSMs on cancer-specific (CSM) and overall (OM) mortality has not yet been proved definitively.
To evaluate whether the presence and the features of PSMs were associated with CSM and OM in patients who underwent robotic-assisted RP.
A cohort of 8141 patients underwent robotic-assisted RP with >10 yr of follow-up.
Cox multivariable analyses assessed the impact of margin status (positive vs negative) and PSM features (negative vs <3 mm vs >3 mm vs multifocal) on the risk of CSM, OM, and biochemical recurrence (BCR) after adjusting for potential confounders. We repeated our analyses after stratifying patients according to clinical (Cancer of the Prostate Risk Assessment CAPRA categories) and pathological characteristics (adverse: pT 3–4 and/or grade group GG 4–5 and/or pN1 and/or prostate-specific antigen PSA persistence).
PSMs were found in 1348 patients (16%). Among these, 48 (3.6%) patients had multifocal PSMs. Overall, 1550 men experienced BCR and 898 men died, including 130 for prostate cancer. At Cox multivariable analyses, PSMs were associated with CSM in patients with adverse clinical (Intermediate risk: hazard ratio HR: 1.71, p = 0.048; high risk: HR: 2.20, p = 0.009) and pathological (HR: 1.79, p = 0.005) characteristics. Only multifocal PSMs were associated with CSM and OM in the whole population (HR for CSM: 4.68, p < 0.001; HR for OM: 1.82, p = 0.037) and in patients with adverse clinical (intermediate risk: HR for CSM: 7.26, p = 0.006; high risk: HR for CSM: 9.26, p < 0.001; HR for OM: 2.97, p = 0.006) and pathological (HR for CSM: 9.50, p < 0.001; HR for OM: 2.59, p = 0.001) characteristics. Potential limitations include a selection bias and a lack of information on the Gleason score at PSM location.
We did not find an association between unifocal PSMs and mortality. Conversely, our results underscore the importance of avoiding multifocal PSMs in patients with adverse clinical (intermediate- and high-risk CAPRA score) and pathological (GG ≥4, pT ≥3, pN1, or PSA persistence) characteristics, to enhance overall survival and reduce CSM.
In this study, we evaluated whether the presence and the characteristics of positive surgical margins were associated with mortality in patients who underwent robotic-assisted radical prostatectomy. We found that the presence of positive surgical margins, particularly multifocal margins, was associated with mortality only in patients with adverse clinical and pathological characteristics.
In the present study, we reported the outcomes of patients with prostate cancer who underwent robot-assisted radical prostatectomy between 10 and 20 yr ago, and we found a very low probability of ...dying for prostate cancer in patients with low- and intermediate-risk disease. In contrast, high-risk patients face a significantly higher risk of prostate cancer mortality.
Evidence on long-term oncological efficacy is available only for open radical prostatectomy but remains scarce for robot-assisted radical prostatectomy (RARP).
To validate the long-term survival rates after RARP and provide stratified outcomes based on contemporary prostate cancer (PCa) risk-stratification tools.
A retrospective analysis of the European Association of Urology (EAU) Robotic Urology Section Scientific Working Group international multicenter database for RARP was performed. Patients who underwent RARP at seven pioneer robotic urology programs in Europe and the USA between 2002 and 2012 were included.
The primary outcomes were PCa-specific mortality and all-cause mortality. The probability of cancer-specific survival (CSS) was estimated with the competing risks method, and the probability of overall survival (OS) was estimated with the Kaplan-Meier method.
A total of 9876 patients who underwent RARP between 2002 and 2012 were included. Within follow-up, 1071 deaths occurred and 159 were due to PCa. At 15 yr of follow-up, CSS and OS were 97.6% (97.2%, 98.0%) and 85.5% (84.6%, 86.4%), respectively. Stratified analyses based on EAU risk groups at diagnosis and pT stage showed favorable survival rates, with low-risk (n = 4601, 46.6%), intermediate-risk (n = 4056, 41.1%), and high-risk (n = 1219, 12.3%) patients demonstrating CSS rates of 99%, 98%, and 90% at 15 yr, respectively. Notably, patients with pT3a disease had similar survival outcomes to those with pT2 disease, with worse CSS in patients with pT3b PCa (98.9% vs 97.4% vs 86.5%). Multivariable analyses identified age, prostate-specific antigen, biopsy Gleason grade group, clinical T stage, and treatment year as independent predictors of worse oncological outcomes.
Our multicenter study with long-term follow-up confirms favorable survival outcomes after RARP for localized PCa. Patients with low- and intermediate-risk disease face a higher risk of mortality from causes other than PCa. On the contrary, high-risk patients have a significantly higher risk of PCa-specific mortality.
In the present study, we reported the outcomes of patients with prostate cancer (PCa) who underwent robot-assisted radical prostatectomy between 10 and 20 yr ago, and we found a very low probability of dying from PCa in patients with low- and intermediate-risk PCa.
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