Roles of PD-L1 in human adipose-derived mesenchymal stem cells under inflammatory microenvironment.

Mesenchymal stem cells (MSCs) display unique homing and immunosuppression features which make them promising candidates for cell therapy in inflammatory disorders. It is known that C-X-C chemokine receptor type 4 (CXCR4, also known as CD184) is a critical receptor implicated in MSCs migration, and the protein programmed death ligand-1 (PD-L1) is involved in MSC's immunosuppression. However, it remains unclear how the molecular mechanisms regulate PD-L1 expression for migration and immunosuppression of MSCs under the inflammatory microenvironment. In this article, we used the human adipose-derived mesenchymal stem cells (hADMSCs) treated with lipopolysaccharide (LPS) as an in vitro inflammatory model to explore the roles of PD-L1 on the migration and immunosuppression of MSC. Our results demonstrate that in hADMSCs, LPS significantly increased PD-L1 expression, which mediated the migration of the LPS-treated hADMSCs via CXCR4. In addition, we found that the increased PD-L1 expression in the LPS-treated hADMSCs inhibited B cell proliferation and immunoglobulin G secretion through nuclear factor-κB. Our study suggests that the PD-L1 plays critical roles in the homing and immunosuppression of MSCs which are a promising cell therapy to treat inflammatory diseases.

Two-year neurodevelopmental outcomes of preterm infants who received red blood cell transfusion.

BACKGROUND: Studies aimed at reducing neonatal anaemia or transfusing higher blood volumes did not find improvement in neurodevelopmental function at two years of age. This study investigated the relationship between the receipt, timing, and number of red blood cell (RBC) transfusions and neurodevelopmental outcomes among preterm infants. MATERIALS AND METHODS: This is a retrospective review of preterm infants (gestational age <34 weeks) with a full neurodevelopmental assessment at 18-36 months corrected age from October 2008 to September 2020. Bayley Scales of Infant and Toddler Development, third edition and the Modified Checklist for Autism in Toddlers were collected. Multivariable regressions were used to evaluate neurodevelopmental outcomes. RESULTS: 654 preterm infants were evaluated with a mean follow-up of 25 months. 295 infants (45%) received a total of 1,322 blood transfusions. After adjustment for gestational age, baseline morbidity, and socioeconomic status, receipt of RBC transfusion was associated with decreased two-year cognitive and motor function, but not language (p=0.047, 0.025, and 0.879, respectively). There was no significant difference in outcomes between receipt of transfusion in the first week of life compared to after. Number of transfusions was associated with decreased cognitive, language, and motor function (all p<0.001), and increased likelihood to develop severe neurodevelopmental impairment (adjusted-odds ratio, 1.09; 95% confidence interval, 1.03-1.15; p=0.004). DISCUSSION: Our study demonstrates an association between RBC transfusion and lower cognitive and motor outcomes at two-years after adjustment for prematurity and illness at birth. Increasing number of transfusions worsened neurodevelopmental outcomes.

Long-term neurodevelopmental outcomes among preterm infants born to mothers with diabetes mellitus.

BACKGROUND: The long-term effects of maternal diabetes on preterm infant neurodevelopment are unknown. This study aims to determine if there was an increased likelihood of neurodevelopmental impairment in preterm infants born to mothers with diabetes. MATERIALS AND METHODS: A retrospective cohort study was conducted on preterm infants with neurodevelopmental evaluations at 18-36 months corrected age using the Bayley Scales of Infant and Toddler Development Third edition. RESULTS: 680 former preterm infants were evaluated. There was no difference in cognitive, language, and motor scores. Infants born to diabetic mothers with AMA were significantly different in cognitive (adjusted-ß (a-ß),-7.24 [95%CI, -11.719 to -2.769]; P = 0.002) and language domains (a-ß,-7.783 [95%CI, -13.603 to -1.963]; (P = 0.009). DISCUSSION: There was no significant difference in neurodevelopmental outcomes of preterm infants exposed to maternal diabetes. Preterm infants born to mothers with diabetes and AMA demonstrated lower cognitive and language scores at 2 years corrected age.

Robot-Assisted Partial Nephrectomy for Totally Endophytic Renal Tumors: Step by Step Standardized Surgical Technique and Long-Term Outcomes with a Median 59-Month Follow-Up.

BACKGROUND: Treatment of totally endophytic renal tumors is a technically demanding surgery. While few studies show promising perioperative and short-term outcomes of robot-assisted partial nephrectomy (RAPN), its long-term outcomes remain undetermined. MATERIALS AND METHODS: A retrospective analysis of 89 patients with totally endophytic renal tumors undergoing either RAPN (n = 52) or open partial nephrectomy (OPN; n = 37) in a tertiary-care institution between 2005 and 2015 was performed. Primary endpoint was to describe our transperitoneal RAPN surgical technique, while secondary endpoint was to compare the 5-year chronic kidney disease (CKD)-free survival, cancer-specific survival (CSS), and metastasis-free survival (MFS) rates between RAPN and OPN. RESULTS: The median follow-up was 59 and 53 months for RAPN and OPN, respectively. Apart from increased prevalence of high complex tumors among RAPN cases (RAPN, 38.5% versus OPN, 16.2%; P = .037), and lower median eGFR (RAPN, 86 versus OPN 96 mL/minute/1.73 m2; P = .032), the remaining demographic characteristics were similar between the groups. At latest follow-up, the rates of local recurrence (P = .577), distant metastasis (P = .854), and cancer death (P = .187), and CKD upstaging ≥stage 3 (P = .728) did not differ between groups. The 5-year CKD upstaging-free survival was 96.2% versus 94.6% (log-rank, P = .746), MFS was 95.8% versus 97.1% (P = .876), and CSS was 100% versus 93.8% (log-rank, P = .102) when stratified by RAPN and OPN, respectively. CONCLUSION: RAPN is a safe and feasible option for treatment of totally endophytic renal tumors. Despite the increased prevalence of high tumor complexity and lower baseline renal function in the RAPN group, it achieved equivalent long-term oncologic control and functional outcome compared to OPN.

Estimated glomerular filtration rate's time to nadir after robot-assisted partial nephrectomy: Predictors and clinical significance on renal functional recovery.

OBJECTIVES: To investigate the impact of postoperative time to nadir of estimated glomerular filtration rate on renal functional changes after robot-assisted partial nephrectomy. METHODS: From 2006 to 2015, 287 patients with renal mass who underwent robot-assisted partial nephrectomy in a referral center were analyzed. The cohort was evaluated based on their time to develop nadir: group 1 (no nadir), group 2 (<48 h) and group 3 (≥48 h). The outcome measures were to evaluate the renal function recovery between groups, risk factors for development of nadir ≥48 h, as well as predictors of chronic kidney disease upstaging. RESULTS: The mean estimated glomerular filtration rate percentage change was the worst in group 3 compared with groups 1 and 2, with 13.8%, -0.67% and 8%, respectively (P < 0.001). Chronic kidney disease upstaging was more common in group 3 compared with the other groups (P < 0.001). Age, tumor size, PADUA score and warm ischemia time were predictors of developing ≥48 h estimated glomerular filtration rate nadir (odds ratio 1.04, P = 0.002; odds ratio 1.43, P < 0.001; odds ratio 1.24, P = 0.018; odds ratio 1.05, P < 0.001), respectively. The 5-year probability of freedom from chronic kidney disease upstaging was lower in group 3 (75.6%) compared with the other groups - 88.1% and 100% (P = 0.003). Time to nadir ≥48 h was a predictor of chronic kidney disease upstaging (odds ratio 3.02, P = 0.022). CONCLUSIONS: A continuous decline in estimated glomerular filtration rate (≥48 h) after partial nephrectomy is associated with increased risk of poor functional recovery overtime. Age, tumor size, PADUA score and warm ischemia time are independent predictors of developing ≥48 h time to nadir of estimated glomerular filtration rate. This higher risk subgroup should be targeted for stricter follow up to allow early detection of future risk of renal functional decline.

Off-Clamp Robot-Assisted Partial Nephrectomy: How Far Shall We Proceed?

BACKGROUND: Off-clamp robot-assisted partial nephrectomy (RAPN) is associated with increased intraoperative blood loss compared with on-clamp technique. Our aim was to demonstrate our surgical technique and to determine which tumors are ideally suited for this technique. METHODS: Sixty-two patients who underwent off-clamp RAPN for renal tumor between 2006 and 2016 were retrospectively analyzed. Increased estimated blood loss (EBL) volume was defined as more than 75 percentile. receiver operating characteristic (ROC) analysis was used to determine exact cut-off tumor size and the preoperative aspects and dimensions used for an anatomical (PADUA) score that are associated with increased EBL. Risk factors for increased EBL >400 mL and chronic kidney disease (CKD) upstaging were evaluated using logistic regression analysis. RESULTS: The median follow-up period was 20 months (interquartile range [IQR]: 12-84). Patient's mean age, mean tumor size, and mean body mass index were 53.5 ± 12.2 years, 2.6 ± 1.5 cm, and 25 ± 4.1 kg/m2, respectively. Median EBL volume was 200 mL (IQR: 100-400). ROC analysis showed that tumor size of 3.2 cm (area under the curve [AUC] = 0.82, P < .001) and PADUA score of 9 (AUC = 0.79, P = .001) were cut-off values for increased EBL >400 mL. Patients with tumor size >3.2 cm had longer operative time (116 versus 163 minutes, P = .002), more EBL (150 versus 575 mL, P < .001), and higher blood transfusion rate (0% versus 18.8%, P = .015), with increased tendency of conversion to radical nephrectomy (0% versus 12.5%, P = .063) compared with tumor size ≤3.2 cm. Overall CKD upstaging was present in 22 patients (35.4%). Multivariable logistic regression analysis showed that EBL >400 mL was the only predictor of CKD upstaging (odds ratio: 6.704, P = .009). CONCLUSIONS: Our study showed that the risk of intraoperative bleeding and transfusion rate during off-clamp RAPN is increased if tumor size >3.2 cm and/or PADUA complexity score ≥9. Moreover, EBL >400 mL was a risk factor of CKD upstaging, despite zero ischemia. Further larger prospective studies are warranted to validate our results.

Prostate-specific antigen 10-20 ng/mL: A predictor of degree of upgrading to ≥8 among patients with biopsy Gleason score 6.

PURPOSE: This study aimed to identify the predictors of upgrading and degree of upgrading among patients who have initial Gleason score (GS) 6 treated with robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: A retrospective review of the data of 359 men with an initial biopsy GS 6, localized prostate cancer who underwent RARP between July 2005 to June 2010 was performed. They were grouped into group 1 (nonupgrade) and group 2 (upgraded) based on their prostatectomy specimen GS. Logistic regression analysis of studied cases identified significant predictors of upgrading and the degree of upgrading after RARP. RESULTS: The mean age and prostate-specific antigen (PSA) was 63±7.5 years, 8.9±8.77 ng/mL, respectively. Median follow-up was 59 months (interquartile range, 47-70 months). On multivariable analysis, age, PSA, PSA density and ≥2 cores positive were predictors of upgrading with (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06; p=0.003; OR, 1.006; 95% CI, 1.01-1.11; p=0.018; OR, 0.65; 95% CI, 0.43-0.98, p=0.04), respectively. On subanalysis, only PSA level of 10-20 ng/mL is associated with upgrading into GS ≥8. They also had lower biochemical recurrence free survival, cancer specific survival, and overall survival (p≤0.001, p=0.003, and p=0.01, respectively). CONCLUSIONS: Gleason score 6 patients with PSA (10-20 ng/mL) have an increased risk of upgrading to pathologic GS (≥8), subsequently poorer oncological outcome thus require a stricter follow-up. These patients should be carefully counseled in making an optimal treatment decision.

Perioperative and short-term outcomes of Retzius-sparing robot-assisted laparoscopic radical prostatectomy stratified by gland size.

OBJECTIVE: To investigate the effect of preoperative prostate volume (PV) on the perioperative, continence and early oncological outcomes among patients treated with Retzius-sparing robot-assisted laparoscopic radical prostatectomy (RS-RALP). PATIENTS AND METHODS: This is a retrospective analysis of 294 patients with organ-confined prostate cancer treated with RS-RALP in a high-volume centre from November 2012 to February 2015. Patients were divided into three groups based on their transrectal ultrasonography estimated PV as follows: group 1, <40 mL (231 patients); group 2, 40-60 mL (47); group 3, >60 mL (16). Perioperative, oncological, and continence outcomes were compared between the three groups. RESULTS: The median [interquartile range (IQR)] PV for each group was; 26.1 (22-31) mL, 45.9 (41-50) mL, and 70 (68-85) mL. Blood loss was higher in group 3 compared to groups 2 and 1; at a median (IQR) of 475 (312-575) mL, 200 (150-400) mL, and 250 (150-400) mL, respectively (P = 0.001). The intraoperative transfusion rate was higher in group 3 patients (P = 0.004), while the complication rate did not differ (P = 0.05). The console time was slightly higher but was not statistically significant in group 3 compared to groups 2 and 1; at a mean (sd) of 100 (35) min, 92 (34.4) min, and 93 (24.8) min, respectively (P = 0.70). Biochemical recurrence and the continence rate did not differ between the three groups (P = 0.89 and P = 0.25, respectively). CONCLUSION: RS-RALP is oncologically and functionally equivalent for all prostate sizes but technically demanding for larger prostates. We therefore recommend that surgeons initiate their RS-RALP technique with smaller prostates.

Robot-assisted partial nephrectomy confers excellent long-term outcomes for the treatment of complex cystic renal tumors: Median follow up of 58 months.

OBJECTIVES: To analyze long-term outcomes of robot-assisted partial nephrectomy for treatment of complex cystic renal tumors. METHODS: We retrospectively analyzed the data of patients who underwent robot-assisted partial nephrectomy for cystic (n = 32) and solid (n = 263) renal masses at Severance Hospital, Seoul, Korea. The primary outcome was assessment of perioperative safety for cystic tumor. Secondary outcomes were evaluation of long-term oncological and functional results. RESULTS: Patients' clinical and demographic characteristics were similar among both groups. The median follow up of cystic and solid masses were 58 and 46 months, respectively. Cystic masses were more likely to have low Fuhrman grade 1 and 2 (P = 0.03), and shorter operative time (P = 0.04) compared with solid masses. There was no statistically significant difference regarding warm ischemia time, estimated blood loss, trifecta achievement, length of hospital stay, complication rates and renal function preservation (P > 0.05) between groups. In the solid group, 12 patients (4.1%) recurred, and six patients (2%) died from metastatic renal cell carcinoma, whereas the patients in the cystic group did not have any local or distance recurrence, and the survival rates were 100%. The 5-year cancer-free survival (P = 0.77), cancer-specific survival (P = 0.65) and overall survival (P = 0.83) rates were similar between the groups. CONCLUSION: Robot-assisted partial nephrectomy appears to be safe and feasible treatment for complex cystic renal masses. It confers excellent long-term oncological outcomes. Robot-assisted partial nephrectomy should be the treatment of choice for complex cysts whenever feasible.