Ten-Year Oncologic Outcomes Following Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: Radical cystectomy is the gold standard for nonmetastatic muscle invasive bladder cancer and for refractory nonmuscle invasive disease. Compared to open radical cystectomy, robot-assisted radical cystectomy has been shown to provide comparable early oncologic outcomes and improved perioperative outcomes. However, there is a paucity of data on long-term oncologic outcomes and concerns about a higher incidence of local recurrence after robot-assisted radical cystectomy. We report 10-year oncologic outcomes following robot-assisted radical cystectomy using a multinational database. MATERIALS AND METHODS: We retrospectively reviewed the prospective International Robotic Cystectomy Consortium database. Consecutive patients who underwent robot-assisted radical cystectomy 10 years ago or earlier were included in analysis. Data were reviewed for demographics, and perioperative, pathological and oncologic outcomes. Kaplan-Meier curves were used to depict recurrence-free, disease specific and overall survival. Multivariate stepwise Cox regression models were applied to identify variables associated with recurrence-free, disease specific and overall survival. RESULTS: We identified 446 patients with a median age of 67 years (IQR 59-76). Of the patients 10% received neoadjuvant chemotherapy, 51% experienced any complication, 23% had high grade complications and 4% died within 3 months of robot-assisted radical cystectomy. Disease was pT3 or greater in 43% of patients and pN+ in 24% while a positive soft tissue surgical margin was observed in 7%. At a median followup of 5 years (IQR 2-10, maximum 14) local and distant recurrence had developed in 15% and 29% of patients, respectively. Ten-year recurrence-free, disease specific and overall survival rates were 59%, 65% and 35%, respectively. Patients with pT3 or greater and pN+ disease showed worse recurrence-free, disease specific and overall survival. CONCLUSIONS: Long-term oncologic outcomes, and recurrence rates and patterns after robot-assisted radical cystectomy seem comparable to those in open series. Advanced disease stage and positive surgical margins remain the main determinants of survival after radical cystectomy.

Iodine status and associations with feeding practices and psychomotor milestone development in six-month-old South African infants.

Iodine is important for normal growth and psychomotor development. While infants below 6 months of age receive iodine from breast milk or fortified infant formula, the introduction of complementary foods poses a serious risk for deteriorating iodine status. This cross-sectional analysis assessed the iodine status of six-month-old South African infants and explored its associations with feeding practices and psychomotor milestone development. Iodine concentrations were measured in infant (n = 386) and maternal (n = 371) urine (urinary iodine concentration [UIC]), and in breast milk (n = 257 [breast milk iodine concentrations]). Feeding practices and psychomotor milestone development were assessed in all infants. The median (25th-75th percentile) UIC in infants was 345 (213-596) µg/L and was significantly lower in stunted (302 [195-504] µg/L) than non-stunted (366 [225-641] µg/L) infants. Only 6.7% of infants were deficient. Maternal UIC (128 [81-216] µg/L; rs  = 0.218, p < 0.001) and breast milk iodine concentrations (170 [110-270] µg/kg; rs  = 0.447, p < 0.0001) were associated with infant UIC. Most infants (72%) were breastfed and tended to have higher UIC than non-breastfed infants (p = 0.074). Almost all infants (95%) consumed semi-solid or solid foods, with commercial infant cereals (60%) and jarred infant foods (20%) being the most common solid foods first introduced. Infants who reported to consume commercial infant cereals ≥4 days weekly had significantly higher UIC (372 [225-637] µg/L) than those reported to consume commercial infant cereals seldom or never (308 [200-517] µg/L; p = 0.023). No associations between infant UIC and psychomotor developmental scores were observed. Our results suggest that iodine intake in the studied six-month-old infants was adequate. Iodine in breast milk and commercial infant cereals potentially contributed to this adequate intake.

Effect of African leafy vegetables on the micronutrient status of mildly deficient farm-school children in South Africa: a randomized controlled study.

OBJECTIVE: A randomized controlled trial was conducted to assess the effect of African leafy vegetable (ALV) consumption on Fe, Zn and vitamin A status in children. DESIGN: Children were randomly allocated to receive either a 300 g cooked ALV dish and school meal starch (n 86) or the normal school meal (n 81) five times per week for three months. ALV in the dish consisted mainly of Amaranthus cruentus (at least 80 %) and the remainder of Cleome gynandra, Cucurbita maxima or Vigna unguiculata. Nutrient content and consumer acceptance of the ALV dish were also determined. SETTING: North West Province, South Africa. SUBJECTS: Grade R to grade 4 children (6-12 years old) of two farm schools. RESULTS: The ALV dish contributed 11·6-15·8 mg Fe and 1·4-3·7 mg Zn. At baseline, prevalence of deficiencies in the intervention group was 16·0 %, 16·3 %, 7·0 % and 75·6 %, respectively, for anaemia (Hb<11·5 g/dl), Fe (serum ferritin<15 µg/l), vitamin A (serum retinol<20 µg/dl) and Zn (serum Zn<65 µg/dl); and in the control group 10·5 %, 18·5 %, 2·5 % and 75·3 %, respectively. No significant estimated intervention effect was found. CONCLUSIONS: This randomized controlled trial showed that ALV were unable to improve serum retinol, serum ferritin or Hb if there are only mild deficiencies present. Furthermore, despite the low Zn status in the study population, ALV consumption did not improve serum Zn concentrations either.

Impact of Perioperative Multidisciplinary Rehabilitation Pathway on Early Outcomes after Robot-assisted Radical Cystectomy: A Matched Analysis.

OBJECTIVE: To investigate the effect of incorporating physical rehabilitation, nutrition and psychosocial care as part of the "NEEW" (Nutrition, Exercise, patient Education and Wellness) on perioperative outcomes after robot-assisted radical cystectomy. METHODS: Patients were divided into 2 groups: pathway group (NEEW in addition to enhanced recovery after surgery), vs prepathway group, before NEEW initiation (enhanced recovery after surgery only). Propensity score matching was performed (ratio 1:2 ratio). Perioperative outcomes were analyzed and compared. Multivariate analyses were modeled to assess for association between NEEW pathway and postoperative outcomes. RESULTS: One hundred and niney-two were included in the study: 64 patients (33%) in the pathway group vs 128 patients (67%) in the prepathway group. Pathway group had shorter median inpatient stay (5 vs 6 days, P <.01), faster bowel recovery (3 vs 4 days, P <.01), and better pain scores, and demonstrated fewer 30-day high grade complications (5% vs 16%, P = .02). On multivariate analysis, the NEEW pathway was associated with shorter hospital stay (1.75 days shorter), faster bowel recovery (1 day faster), longer functional mobility time (4 minutes longer) and less pain scores (average 1 point less). CONCLUSION: Standardized perioperative pathway with weekly multidisciplinary team meeting was associated with improved short-term perioperative outcomes after robot-assisted radical cystectomy.

Detailed Analysis of Urinary Tract Infections After Robot-Assisted Radical Cystectomy.

Objective: To describe urinary tract infections (UTIs) after robot-assisted radical cystectomy (RARC) and investigate the variables associated with it. Materials and Methods: A retrospective review of 616 patients who underwent RARC between 2005 and 2019 was performed. Patients were divided into those who developed UTI and those who did not. Patients who developed UTI were further subdivided into three subgroups according to the onset, number, and severity. The Kaplan-Meier method was used to depict time to UTI. Multivariate analysis was used to investigate variables associated with UTI. Result: Two hundred forty (39%) patients were diagnosed with UTI after RARC; 48% occurred within 30 days, 17% within 30-90 days, and 35% at 90 days after RARC. Twenty-three percent of the patients presented with urosepsis. The median (interquartile ratio) time to develop UTI was 1 (0.3-7) month. On multivariate analysis, patients who received neobladders (odds ratio [OR] 2.80; 95% confidence interval [CI] 1.50-5.20; p < 0.01), prolonged hospital stay (OR 1.06; 95% CI 1.03-1.08; p < 0.01), adjuvant chemotherapy (OR 2.20; 95% CI 1.40-3.60; p < 0.01), poor renal function postoperatively (OR 2.30; 95% CI 1.30-3.80; p < 0.01), postoperative hydronephrosis (OR 2.50; 95% CI 1.40-4.50; p < 0.01), ureteroileal anastomotic stricture (OR 2.90; 95% CI 1.50-5.70; p < 0.01), and stented ureteroileal anastomosis (OR 9.35; 95% CI 1.23-71.19; p = 0.03) were associated with UTI after RARC. Conclusion: UTI is common after RARC mainly within the first month after RARC. Enterococcus faecalis was the most common causative organism.

Feasibility and continence outcomes of extended prostatic urethral preservation during robot-assisted radical prostatectomy.

BACKGROUND: The prostatic urethra is conventionally resected during robot-assisted radical prostatectomy (RARP). We describe the technical feasibility and urinary continence outcomes of extended prostatic urethral preservation (EPUP) during RARP. METHODS: A single surgeon at a National Comprehensive Cancer Network institute performed 48 consecutive RARP operations using EPUP from March 2014 to March 2016, during which time 177 conventional non-EPUP RARP operations were performed by other surgeons. Prior to this period, the EPUP surgeon had performed 17 non-EPUP RARP operations over 15 months. Total intracorporeal urethral length (IUL) preserved during EPUP was measured intraoperatively. Associations of EPUP and IUL with continence recovery rates and/or times were tested in Fisher's exact and log rank univariate analyses and Cox logistic regression multivariable analyses. RESULTS: Median IUL preserved during EPUP was 4.0 cm (range 2.5-6.0 cm), and urethral dissections typically spanned the prostatic apex to mid-gland or base. Seven-week continence rates were significantly higher with versus without EPUP. EPUP patient rates of using 0 or 0-1 pads per day immediately after catheter removal were 19% and 35%, respectively. These rates increased significantly (53% and 76%, respectively), as did the IUL preserved (median 5.0 cm), among more recent EPUP patients (n = 17), which suggested a learning curve. In multivariable analyses including all patients, an EPUP approach was an independent predictor of faster continence recovery. In multivariable analyses of the EPUP subset, a longer IUL preserved was independently associated with faster continence recovery. No EPUP patient had a urethral fossa positive margin, and apical positive margins were similarly infrequent among EPUP and non-EPUP patients. CONCLUSIONS: EPUP is technically feasible during RARP and associated with faster continence recovery. Future investigation into the generalizability of these findings and the oncologic safety of EPUP is warranted.

The Effect of Complexity of the Surgical Field on Perioperative Outcomes of Robot-Assisted Radical Cystectomy.

OBJECTIVE: To report the outcomes of patients who underwent robot-assisted radical cystectomy (RARC) and have a history of previous pelvic surgery and/or radiation. METHODS: Retrospective review of our prospectively maintained database between 2005 and 2018. Patients were divided into 3 groups based on surgical complexity; Complexity grade 1 included patients who did not have any history of prior pelvic surgery or radiation (n = 323); Complexity grade 2 included those who had history of a single pelvic surgery or radiation (n = 186); and Complexity grade 3 included those who had history of 2 or more pelvic surgeries, or one or more pelvic surgery and radiation (n = 80). All groups were compared in terms of perioperative outcomes. Multivariate linear and logistic regression models were used to depict the predictors of operative time, ≥500 ml blood loss, 90-day complications, high grade complications, and readmissions. RESULTS: Complexity grades 2 and 3 exhibited higher 90-day complications compared to CG1 (CG3: 74%, CG1: 59%, CG2: 68%, P = .02), and high grade complications (CG3: 24%, CG1: 13%, CG2 18%, P = .03). On multivariate linear and logistic regression models, CG 3 was significantly associated with higher 90-day complications (OR 2.18, 95% CI 1.21-3.94, P <.01) but not significantly associated with higher rates of significant blood loss, longer operative time, 90-day high grade complications and readmissions. CONCLUSION: Patients with higher complexity of the surgical field exhibited more complications after robot-assisted radical cystectomy, but not readmissions.

Development and Cross-Validation of a Nomogram for Chronic Kidney Disease Following Robot-Assisted Radical Cystectomy.

Introduction: We sought to identify the factors associated with deterioration of renal functions after robot-assisted radical cystectomy, and to develop a nomogram to detect the probability of progression to chronic kidney disease (CKD). Materials and Methods: A retrospective review of our prospectively maintained database. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epidemiology Collaboration creatinine formula utilizing all follow-up creatinine values. CKD was defined as stage 3b (eGFR <45 mL/minute/1.73 m2) based on the National Kidney Foundation classification. Kaplan-Meier curves were used to depict CKD-free survival. A multivariate Cox regression model was used to determine predictors for CKD and to build the perioperative nomogram. Results: The data set comprised 442 patients with a median follow-up of 25 months (12-59). Thirty-seven percent developed CKD at a median of 9 months (4-18). CKD-free survival rates at 1, 3, and 5 years were 75%, 58%, and 50%, respectively. CKD was significantly associated with preoperative eGFR (hazards ratio [HR]: 0.96, 95% confidence interval [CI]: 0.95-0.97, p < 0.01), body mass index (HR: 1.03, 95% CI: 1.01-1.05, p = 0.03), Charlson Comorbidity Index ≥3 (HR: 2.20, 95% CI: 1.35-3.58, p < 0.01), diabetes (HR: 1.59, 95% CI: 1.09-2.31, p = 0.02), 90 days postoperative strictures (HR: 4.04, 95% CI: 1.76-9.30, p < 0.01), 90 days postoperative hydronephrosis (HR: 2.26, 95% CI: 1.34-3.79, p < 0.01), 90 days recurrent urinary tract infection (HR: 1.84, 95% CI: 1.08-3.14, p = 0.02), 90 days acute kidney injury (HR: 1.70, 95% CI: 1.19-2.43, p < 0.01), and node positive disease (HR: 1.94, 95% CI: 1.31-2.86, p < 0.01). A 5-year CKD-free survival nomogram was developed. Conclusion: We have developed and cross-validated a nomogram for detecting CKD-free survival. This nomogram may have a role in counseling and follow up of patients. This study was done after the approval of the IRB committee (I-79606).

Circulating microRNAs as biomarkers in traumatic brain injury.

Preclinical and clinical studies can be greatly improved through the inclusion of diagnostic, prognostic, predictive or pharmacodynamics biomarkers. Circulating microRNAs (miRNAs) represent highly stable targets that respond to physiological and pathological changes. MicroRNA biomarkers can be detected by highly sensitive and absolutely quantitative methods currently available in most clinical laboratories. Here we review preclinical and clinical studies that have examined circulating miRNAs as potential diagnostic and prognostic biomarkers. We also present data that suggests pharmacodynamics biomarkers can be identified that are associated with neuroprotection in general. Although circulating miRNA can serve as useful tools, it is clear their expression profiles are highly sensitive to changing conditions and are influenced by a broad range of parameters including age, sex, body mass index, injury severity, time of collection, as well as methods of processing, purification and detection. Thus, considerable effort will be required to standardize methods and experimental design conditions before circulating miRNAs can prove useful in a heterologous injury like TBI. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".

Thymosin beta 4 induces significant changes in the plasma miRNA profile following severe traumatic brain injury in the rat lateral fluid percussion injury model.

OBJECTIVES: Thymosin beta 4 (Tß4) has demonstrated neuroprotective potential in models of neurlogical injury. The neuroprotective potential of Tß4 has been associated with increased miR-200a and miR-200b within the brain following stroke. Here we tested the hypothesis that Tß4 treatment could also alter miRNA profiles within the plasma following severe traumatic brain injury (TBI). METHODS: We used the rat lateral fluid percusion injury model of severe TBI to test this hypothesis. Highly sensitive and quantitative droplet digital polymerase chain reaction (ddPCR) was used to measure the plasma concentrations of miR-200 family members. In addition, we conducted RNAseq analysis of plasma miRNA to further identify changes associated with TBI and treatment with Tß4. RESULTS: ddPCR demonstrated that miR-200a-3p andmiR-200b-3p were both significantly increased in plasma following treatment with Tß4 after severe TBI. RNAseq analysis suggested that miR-300-3p and miR-598-3p increased while miR-450-3p and miR-194-5p significantly decreased following TBI. In contrast, miR-194-5p significantly increased in Tß4 treated rats following TBI. In addition, we identified nine plasma miRNAs whose expression significantly changed following treatment with Tß4. CONCLUSIONS: Tß4 treatment significantly increased plasma levels of miR-200a-3p and miR-200b-3p, while RNAseq analysis identified miR-194-5p as a candidate miRNA that may be critical for neuroprotection.

Breast-Milk Iodine Concentrations, Iodine Status, and Thyroid Function of Breastfed Infants Aged 2-4 Months and Their Mothers Residing in a South African Township.

OBJECTIVE: Lactating women and their infants are susceptible to iodine deficiency and iodine excess. In South Africa, no data exist on the iodine status and thyroid function of these vulnerable groups. METHODS: In a cross-sectional study, urinary iodine concentrations (UIC), thyroid function, and breast-milk iodine concentrations (BMIC) were assessed in 100 lactating women from a South African township and their 2-4-month-old breastfed infants. Potential predictors of UIC, thyroid function, and BMIC, including household salt iodine concentrations (SIC) and maternal sodium excretion, were also investigated. RESULTS: The median (25th-75th percentile) UIC was 373 (202-627) µg/L in infants and 118 (67-179) µg/L in mothers. Median household SIC was 44 (27-63) ppm. Household SIC and maternal urinary sodium excretion predicted UIC of lactating mothers. Median BMIC was 179 (126-269) µg/L. Age of infants, SIC, and maternal UIC predicted BMIC. In turn, infant age and BMIC predicted UIC of infants. Forty-two percent of SIC values were within the South African recommended salt iodine fortification level at production of 35-65 ppm, whilst 21% of SIC were >65 ppm. Thyroid-stimulating hormone, total thyroxine, and thyroglobulin concentrations in the dried whole blood spot specimens from the infants were 1.3 (0.8-1.9) mU/L, 128±33 mmol/L, and 77.1 (56.3-105.7) µg/L, respectively, and did not correlate with infant UIC or BMIC. CONCLUSION: Our results suggest that the salt fortification program in South Africa provides adequate iodine to lactating women and indirectly to their infants via breast milk. However, monitoring of salt iodine content of the mandatory salt iodization program in South Africa is important to avoid over-iodization of salt.

Optimization of a New Mass Spectrometry Method for Measurement of Breast Milk Iodine Concentrations and an Assessment of the Effect of Analytic Method and Timing of Within-Feed Sample Collection on Breast Milk Iodine Concentrations.

BACKGROUND: Breast milk iodine concentration (BMIC) may be an indicator of iodine status during lactation, but there are few data comparing different analytical methods or timing of sampling. The aims of this study were: (i) to optimize a new inductively coupled plasma mass spectrometry (ICP-MS) method; and (ii) to evaluate the effect of analytical method and timing of within-feed sample collection on BMIC. METHODS: The colorimetric Sandell-Kolthoff method was evaluated with (a) or without (b) alkaline ashing, and ICP-MS was evaluated using a new (129)I isotope ratio approach including Tellurium (Te) for mass bias correction (c) or external standard curve (d). From iodine-sufficient lactating women (n = 97), three samples were collected within one breast-feeding session (fore-, mid-, and hind-feed samples) and BMIC was analyzed using (c) and (d). RESULTS: Iodine recovery from NIST SRM1549a whole milk powder for methods (a)-(d) was 67%, 24%, 105%, and 102%, respectively. Intra- and inter-assay coefficients of variation for ICP-MS comparing (c) and (d) were 1.3% versus 5.6% (p = 0.04) and 1.1% versus 2.4% (p = 0.33). The limit of detection (LOD) was lower for (c) (0.26 µg/kg) than it was for (d) (2.54 µg/kg; p = 0.02). Using (c), the median [95% confidence interval (CI) obtained by bootstrap] BMIC (µg/kg) in foremilk (179 [CI 161-206]) and in mid-feed milk (184 [CI 160-220]) were not significantly different (p = 0.017), but were higher than in hindmilk (175 [CI 153-216]; p < 0.001). In foremilk using (d), BMIC was 199 ([CI 182-257]; p < 0.001 vs. (c)). The variation in BMIC comparing (c) and (d) (13%) was greater than variation within feeding (5%; p < 0.001). CONCLUSIONS: Because of poor recoveries, (a) and (b) should not be used to measure BMIC. Compared with (d), (c) has the advantages of higher precision and a lower LOD. In iodine-sufficient women, BMIC shows low variation within a breast-feeding session, so timing of sampling is not a major determinant of BMIC.

Indigenous and traditional plants: South African parents' knowledge, perceptions and uses and their children's sensory acceptance.

BACKGROUND: The dietary shift from indigenous and traditional plants (ITPs) to cash crops and exotic plant food sources increases the risk of malnutrition and other nutrition-related non-communicable diseases, especially in poor rural communities. Farm communities in South Africa have been associated with poor nutritional status and extreme poverty. ITPs have been found to be affordable sources of several micronutrients. However, knowledge of and the use of these plants are declining, and little is known about the child's acceptance of dishes prepared with ITPs. This knowledge can be used to improve the general acceptance of ITPs. This study aimed to gain insight into parents' knowledge and perceptions and their use of ITPs in a farming community in the North West Province and to assess children's acceptance of and preference for dishes made with African leafy vegetables (ALVs) and Swiss chard. METHODS: Parents (n = 29) responsible for food preparation for children in grade 2 to 4 in two schools were purposively selected for four focus group discussions. A sensory evaluation assessed the children's (n = 98) acceptance of, preference for and intended consumption of dishes made with leafy vegetables. The dishes were made of Amaranthus spp., Cleome gynandra, Cucurbita maxima, Vigna unguiculata and Beta vulgaris. RESULTS: Parents mentioned 30 edible ITPs during the focus group discussions. Parents had knowledge of available ITPs and their use as food. Location, seasonal variation and rainfall affected the availability of and access to ITPs. Sun-dried ITPs were stored in sacks for later use. ITPs were perceived as healthy, affordable and delicious, hence acceptable to the parents. The children also evaluated the dishes made with ALVs as acceptable in terms of colour, smell and taste. Swiss chard was preferred, most likely because of the children's exposure to this vegetable. Children indicated that they would like to eat these leafy vegetables twice a week. CONCLUSION: These results look promising for the promotion of ITPs as a strategy to reduce malnutrition in rural farm communities and for potential inclusion of these micronutrient-rich ALVs in school feeding programmes to improve the nutritional status of children.