PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial.

Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains lethal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated durable remissions in hematological malignancies. We report results from a phase 1, first-in-human study of prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC. The starting dose level (DL) was 100 million (M) CAR T cells without lymphodepletion (LD), followed by incorporation of LD. The primary end points were safety and dose-limiting toxicities (DLTs). No DLTs were observed at DL1, with a DLT of grade 3 cystitis encountered at DL2, resulting in addition of a new cohort using a reduced LD regimen + 100 M CAR T cells (DL3). No DLTs were observed in DL3. Cytokine release syndrome of grade 1 or 2 occurred in 5 of 14 treated patients. Prostate-specific antigen declines (>30%) occurred in 4 of 14 patients, as well as radiographic improvements. Dynamic changes indicating activation of peripheral blood endogenous and CAR T cell subsets, TCR repertoire diversity and changes in the tumor immune microenvironment were observed in a subset of patients. Limited persistence of CAR T cells was observed beyond 28 days post-infusion. These results support future clinical studies to optimize dosing and combination strategies to improve durable therapeutic outcomes. ClinicalTrials.gov identifier NCT03873805 .

Surgical and functional outcomes of Retzius-sparing robotic-assisted radical prostatectomy versus conventional robotic-assisted radical prostatectomy in patients with biopsy-confirmed prostate cancer. Are outcomes worth it? Systematic review and meta-analysis.

BACKGROUND: Radical prostatectomy is the standard of care for prostate cancer. Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) is being widely adopted due to positive functional outcomes compared to conventional robotic-assisted radical prostatectomy (c-RARP). Concerns regarding potency, oncological outcomes, and learning curve are still a matter of debate. METHODS: Following Preferred Instrument for Systematic Reviews and Meta-Analysis guidelines and PROSPERO registration CRD42023398724, a systematic review was performed in February 2023 on RS-RARP compared to conventional c-RARP. Outcomes of interest were continence recovery, potency, positive surgical margins (PSM), biochemical recurrence (BCR), estimated blood loss (EBL), length of stay (LOS), operation time and complications. Data were analyzed using R version 4.2.2. RESULTS: A total of 17 studies were included, totaling 2751 patients, out of which 1221 underwent RS-RARP and 1530 underwent c-RARP. Continence was analyzed using two definitions: zero pad and one safety pad. Cumulative analysis showed with both definitions statistical difference in terms of continence recovery at 1 month (0 pad odds ratio [OR] = 4.57; 95% confidence interval [CI] = [1.32-15.77]; Safety pad OR = 13.19; 95% CI = [8.92-19.49]), as well as at 3 months (0 pad OR, 2.93; 95% CI = [1.57-5.46]; Safety pad OR = 5.31; 95% CI = [1.33-21.13]). Continence recovery at 12 months was higher in the one safety pad group after RS-RARP (OR = 4.37; 95% CI = [1.97-9.73]). The meta-analysis revealed that overall PSM rates without pathologic stage classification were not different following RS-RARP (OR = 1.13; 95% CI = [0.96-1.33]. Analysis according to the tumor stage revealed PSM rates in pT2 and pT3 tumors are not different following RS-RARP compared to c-RARP (OR = 1.46; 95% CI = [0.84-2.55]) and (OR = 1.41; 95% CI = [0.93-2.13]), respectively. No difference in potency at 12 months (OR = 0.98; 95% CI = [0.69-1.41], BCR at 12 months (OR = 0.99; 95% CI = [0.46-2.16]), EBL (standardized mean difference [SMD] = -0.01; 95% CI = [-0.31 to 0.29]), LOS (SMD = -0.01; 95% CI = [-0.48 to 0.45]), operation time (SMD = -0.14; 95% CI = [-0.41 to 0.12]) or complications (OR = 0.9; 95% CI = [0.62-1.29]) were observed. CONCLUSIONS: Our analysis suggests that RS-RARP is safe and feasible. Faster continence recovery rate is seen after RS-RARP. Potency outcomes appear to be similar. PSM rates are not different following RS-RARP regardless of pathologic stage. Further quality studies are needed to confirm these findings.

Living donor robotic-assisted kidney transplant compared to traditional living donor open kidney transplant. Where do we stand now? A systematic review and meta-analysis.

BACKGROUND: Renal transplant is the standard of care for patients with end-stage renal disease (ESRD). Robotic-assisted kidney transplant (RAKT) has emerged as a safe minimally invasive approach with a lower complication rate than open kidney transplant (OKT). Concerns regarding ischemia times and graft function are still a matter of debate. METHODS: Following PRISMA guidelines and PROSPERO registration CRD42023413774, a systematic review was performed in March 2023 on RAKT compared to OKT. Primary outcomes of interest were surgical times, ischemia times, blood loss, complication rates, and graft function. Data were analyzed using R version 4.2.2. RESULTS: A total of nine studies comparing living donor RAKT to living donor OKT were included, totaling 1477 patients, out of which 508 underwent RAKT and 969 OKT. RAKT cases were highly selected as depicted in the manuscript. Cumulative analysis showed significantly longer total ischemic time (MD = 16.51; 95% CI = [9.86-23.16]) and rewarming ischemia time (MD = 11.24; 95% CI = [-0.46-22.01]) in RAKT group. No differences were found in total procedure time and time to complete anastomoses. Blood loss and transfusion rate were lower in RAKT group (MD = -53.68; 95% CI = [-89.78; -17.58]) and (RR = 0.29; 95% CI = [0.14; 0.57]), respectively. The meta-analysis revealed a lower rate of surgical site infection (SSI) (RR = 0.31; 95% CI = [0.19-0.52]) and symptomatic lymphocele (RR = 0.16; 95% CI = [0.06-0.43]) in RAKT. No difference in ileus rate was found. Pain scores were significantly lower in the RAKT group (MD = -1.14; 95% CI = [-1.59 - -0.69]; p ≤0.01). No difference in length of stay and hospital readmission were evidenced. Delayed graft function (DGF) and acute rejection rates were not different between interventions groups (RR =1.23; 95% CI = [0.40-3.74]) and (RR =0.96; 95% CI = [0.55-1.70]), respectively. No difference between groups in early graft outcomes are evident. CONCLUSIONS: Our analysis suggests that RAKT is a minimally invasive, safe, and feasible procedure. It is associated with a lower complication rate and similar intraoperative, perioperative, and postoperative outcomes. Further quality studies are needed to confirm these findings.

Animal models of kidney iron overload and ferroptosis: a review of the literature.

In recent years, it has been identified that excess iron contributes to the development of various pathologies and their complications. Kidney diseases do not escape the toxic effects of iron, and ferroptosis is identified as a pathophysiological mechanism that could be a therapeutic target to avoid damage or progression of kidney disease. Ferroptosis is cell death associated with iron-dependent oxidative stress. To study the effects of iron overload (IOL) in the kidney, numerous animal models have been developed. The methodological differences between these models should reflect the IOL-generating mechanisms associated with human IOL diseases. A careful choice of animal model should be considered for translational purposes.

Nutraceuticals: A Promising Therapeutic Approach in Ophthalmology.

Oxidative stress represents one of the main factors driving the pathophysiology of multiple ophthalmic conditions including presbyopia, cataracts, dry eye disease (DED), glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). Currently, different studies have demonstrated the role of orally administered nutraceuticals in these diseases. For instance, they have demonstrated to improve lens accommodation in presbyopia, reduce protein aggregation in cataracts, ameliorate tear film stability, break up time, and tear production in dry eye, and participate in the avoidance of retinal neuronal damage and a decrease in intraocular pressure in glaucoma, contribute to the delayed progression of AMD, or in the prevention or treatment of neuronal death in diabetic retinopathy. In this review, we summarized the nutraceuticals which have presented a positive impact in ocular disorders, emphasizing the clinical assays. The characteristics of the different types of nutraceuticals are specified along with the nutraceutical concentration used to achieve a therapeutic outcome in ocular diseases.

Empirical Antibiotic Prescribing in Adult COVID-19 Inpatients over Two Years in Mexico.

Background and Objectives: Empirical antibiotic prescribing in patients with coronavirus disease 2019 (COVID-19) has been common even though bacterial coinfections are infrequent. The overuse of antibacterial agents may accelerate the antibiotic resistance crisis. We aimed to evaluate factors predicting empirical antibiotic prescribing to adult COVID-19 inpatients over 2 years (March 2020-February 2021) in Mexico. Materials and Methods: A cross-sectional analysis of a nationwide cohort study was conducted. Hospitalized adults due to laboratory-confirmed COVID-19 were included (n = 214,171). Odds ratios (OR) and 95% confidence intervals (CI), computed by using logistic regression models, were used to evaluate factors predicting empirical antibiotic prescribing. Results: The overall frequency of antibiotic usage was 25.3%. In multiple analysis, the highest risk of antibiotic prescription was documented among patients with pneumonia at hospital admission (OR = 2.20, 95% CI 2.16-2.25). Male patients, those with chronic comorbidities (namely obesity and chronic kidney disease) and longer interval days from symptoms onset to healthcare seeking, were also more likely to receive these drugs. We also documented that, per each elapsed week during the study period, the odds of receiving antibiotic therapy decreased by about 2% (OR = 0.98, 95% CI 0.97-0.99). Conclusion: Our study identified COVID-19 populations at increased risk of receiving empirical antibiotic therapy during the first two years of the pandemic.