Microbiota configuration determines nutritional immune optimization.

Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we propose that DR-induced optimization of immunological memory requires a complex cascade of events involving memory T cells, the intestinal microbiota, and myeloid cells. Our findings suggest that DR enhances the ability of memory T cells to recruit and activate myeloid cells in the context of a secondary infection. Concomitantly, DR promotes the expansion of commensal Bifidobacteria within the large intestine, which produce the short-chain fatty acid acetate. Acetate conditioning of the myeloid compartment during DR enhances the capacity of these cells to kill pathogens. Enhanced host protection during DR is compromised when Bifidobacteria expansion is prevented, indicating that microbiota configuration and function play an important role in determining immune responsiveness to this dietary intervention. Altogether, our study supports the idea that DR induces both memory T cells and the gut microbiota to produce distinct factors that converge on myeloid cells to promote optimal pathogen control. These findings suggest that nutritional cues can promote adaptation and co-operation between multiple immune cells and the gut microbiota, which synergize to optimize immunity and protect the collective metaorganism.

Testicular self-examination for early detection of testicular cancer.

Testicular cancer (TCa) commonly presents as a painless scrotal mass. It has been suggested that testicular self-examination (TSE) can help in early detection and thus potentially improve treatment outcomes and prognosis. While TSE is more well established in guideline recommendations for patients with a known history of TCa, its role in healthy young men is less established and controversial. In this paper, we review contemporary data to provide an updated recommendation.

Immunity to the microbiota promotes sensory neuron regeneration.

Tissue immunity and responses to injury depend on the coordinated action and communication among physiological systems. Here, we show that, upon injury, adaptive responses to the microbiota directly promote sensory neuron regeneration. At homeostasis, tissue-resident commensal-specific T cells colocalize with sensory nerve fibers within the dermis, express a transcriptional program associated with neuronal interaction and repair, and promote axon growth and local nerve regeneration following injury. Mechanistically, our data reveal that the cytokine interleukin-17A (IL-17A) released by commensal-specific Th17 cells upon injury directly signals to sensory neurons via IL-17 receptor A, the transcription of which is specifically upregulated in injured neurons. Collectively, our work reveals that in the context of tissue damage, preemptive immunity to the microbiota can rapidly bridge biological systems by directly promoting neuronal repair, while also identifying IL-17A as a major determinant of this fundamental process.

Two Weeks Too Long: Optimal Duration for Ureteral Prestenting and Its Physiologic Effects on the Ureter in a Yorkshire-Landrace Pig Model.

INTRODUCTION: Prestenting of the ureter is commonly performed to allow for passive dilation and better access to the urinary system during subsequent procedures. There is no level 1 evidence on the duration of prestenting and EAU guidelines suggest a 1-2 weeks duration. MATERIALS AND METHODS: Our primary aim is to investigate the optimal duration required for prestenting in a porcine model. Our secondary aim is to compare the ureteral wall compliance between the stented and the unstented ureters. METHODS: Three female pigs between 40 and 50 kg were used. We modified a human protocol for performing intravenous pyelograms in our study to obtain ureteral measurements on days 0, 5, 7, and 14. Unilateral stenting on days 0, 5, and 7 was performed. On day 14, bilateral nephroureterectomy was performed, and ureteral compliance was measured in the stent and unstented ureter. RESULTS: There were significant ureteral dilation between days 0 and 5 for all three pigs (p1 = 0.001, p2 ≤ 0.001 and p3 = 0.01). The rate of dilation appears to plateau after day 5 (p1 = 0.416, p2 = 0.344, and p3 = 0.774). Ureteral compliance in the stented ureter is better than in a nonstent ureter (p1 = 1.44 vs 0.13, p2 = 0.8 vs 0.04, p3 = 0.62 vs 0.2). An unexpected observation was the ureteral dilation and increased tortuosity in the unstented ureter in two of the three pigs (p1 = 0.152, p2 = 0.007). CONCLUSION: Our results suggest that optimal prestenting may be achieved in 5 days in a porcine model. It can potentially form the basis to start randomized human trials.

Müllerianosis: A Case Report.

Background: Müllerianosis is a rare condition with ∼40 reported cases to date. It presents clinically as hematuria, dysuria, and pelvic pain. It most commonly affects the urinary bladder and affects women of fertile age. Case Presentation: This is a case of a 43-year-old Chinese woman, with a medical history of thyroid cancer post-thyroidectomy. She had no history of gynecologic nor pelvic procedures done. Conclusion: Even though müllerianosis has a benign course, it is important to note that it may also have an atypical presentation such as acute renal colic. Also, malignancy will need to be ruled out as some cases have been associated with malignancy. In this case, the initial CT scan showed adjacent urinary bladder wall thickening near the uterus. This prompted further imaging with MRI to exclude uterine involvement. Fortunately, histology confirmed it to be müllerianosis.

Type IV Pilus Alignment Subcomplex Proteins PilN and PilO Form Homo- and Heterodimers in Vivo.

Pseudomonas aeruginosa is a leading cause of hospital-acquired infections and is resistant to many antibiotics. Type IV pili (T4P) are among the key virulence factors used by P. aeruginosa for host cell attachment, biofilm formation, and twitching motility, making this system a promising target for novel therapeutics. Point mutations in the conserved PilMNOP alignment subcomplex were previously shown to have distinct effects on assembly and disassembly of T4P, suggesting that it may function in a dynamic manner. We introduced mutations encoding Cys substitutions into pilN and/or pilO on the chromosome to maintain normal stoichiometry and expression levels and captured covalent PilNO heterodimers, as well as PilN and PilO homodimers, in vivo Most covalent PilN or PilO homodimers had minimal functional impact in P. aeruginosa, suggesting that homodimers are a physiologically relevant state. However, certain covalent homo- or heterodimers eliminated twitching motility, suggesting that specific PilNO configurations are essential for T4P function. These data were verified using soluble N-terminal truncated fragments of PilN and PilO Cys mutants, which purified as a mixture of homo- and heterodimers at volumes consistent with a tetramer. Deletion of genes encoding alignment subcomplex components, PilM or PilP, but not other T4P components, including the motor ATPases PilB or PilT, blocked in vivo formation of disulfide-bonded PilNO heterodimers, suggesting that both PilM and PilP influence the heterodimer interface. Combined, our data suggest that T4P function depends on rearrangements at PilN and PilO interfaces.

Does body mass index have an impact on the rate and location of positive surgical margins following robot assisted radical prostatectomy?

OBJECTIVE: Obesity has been shown to be associated with more aggressive prostate cancer. We sought to determine whether body mass index (BMI) has an impact on the rate and location of positive surgical margins (PSM) in robot-assisted laparoscopic radical prostatectomy (RLRP). METHODS: Records of patients undergoing RLRP between the years 2003 and 2009 were retrospectively reviewed. We collected data regarding clinicopathologic data (i.e., age, BMI, PSA levels, Gleason score, pathologic stage, surgical margins status, and location). BMI was categorized as <25, 25-30, and >30 Kg/m(2). The rates of overall apical, peripheral, and prostate base (PB) PSM were compared across BMI groups. RESULTS: Overall, 577 records were analyzed. Median age, PSA levels, and BMI were 60.1, 5.3, and 28.2, respectively. Percentage of Gleason score 4, 5, 6, 7, 8, 9 in the entire series was 0.2, 2.1, 40.7, 53, 2.3, and 1.7, respectively. Four hundred eighty-four (81.8%) cases were pathologically organ-confined. The overall incidence of PSM was 23.1% (n = 133) of those 10.2% apical, 3.6% PB and 14.2% peripheral. There were no statistically significant differences found in the rate of PSM by location between BMI groups; however, in the obese group there was a tendency toward slightly higher involvement of the PB with tumor in all stages and greater involvement of all anatomic areas in the T3 pathologic stage. CONCLUSIONS: Although obesity has been associated with more aggressive prostate cancer, BMI does not appear to have statistically significant influence on the rate and location of PSM in RLRP. Larger studies are required to confirm these findings.

Optimization of treatment strategy used during shockwave lithotripsy to maximize stone fragmentation efficiency.

BACKGROUND AND PURPOSE: Previous studies have demonstrated that treatment strategy plays a critical role in ensuring maximum stone fragmentation during shockwave lithotripsy (SWL). We aimed to develop an optimal treatment strategy in SWL to produce maximum stone fragmentation. MATERIALS AND METHODS: Four treatment strategies were evaluated using an in-vitro experimental setup that mimics stone fragmentation in the renal pelvis. Spherical stone phantoms were exposed to 2100 shocks using the Siemens Modularis (electromagnetic) lithotripter. The treatment strategies included increasing output voltage with 100 shocks at 12.3 kV, 400 shocks at 14.8 kV, and 1600 shocks at 15.8 kV, and decreasing output voltage with 1600 shocks at 15.8 kV, 400 shocks at 14.8 kV, and 100 shocks at 12.3 kV. Both increasing and decreasing voltages models were run at a pulse repetition frequency (PRF) of 1 and 2 Hz. Fragmentation efficiency was determined using a sequential sieving method to isolate fragments less than 2 mm. A fiberoptic probe hydrophone was used to characterize the pressure waveforms at different output voltage and frequency settings. In addition, a high-speed camera was used to assess cavitation activity in the lithotripter field that was produced by different treatment strategies. RESULTS: The increasing output voltage strategy at 1 Hz PRF produced the best stone fragmentation efficiency. This result was significantly better than the decreasing voltage strategy at 1 Hz PFR (85.8% vs 80.8%, P=0.017) and over the same strategy at 2 Hz PRF (85.8% vs 79.59%, P=0.0078). CONCLUSIONS: A pretreatment dose of 100 low-voltage output shockwaves (SWs) at 60 SWs/min before increasing to a higher voltage output produces the best overall stone fragmentation in vitro. These findings could lead to increased fragmentation efficiency in vivo and higher success rates clinically.

Pathologic evaluation of hemostatic agents in percutaneous nephrolithotomy tracts in a porcine model.

BACKGROUND AND PURPOSE: Hemostatic agents have been suggested as an adjunct for tubeless percutaneous nephrolithotomy (PCNL). We pathologically evaluated the percutaneous tracts injected with the fibrin sealant (FS) Evicel and hemostatic gelatin matrix (HGM) Surgiflo at various time intervals to determine their absorption and tract closure rates. We also evaluated whether these agents reduced urine leak rates in a porcine model. MATERIALS AND METHODS: Percutaneous access was obtained in 19 kidneys in 10 domestic swine. The tracts were dilated to 30F using a balloon dilating catheter. Ten kidneys served as controls. Surgiflo was injected into the tract of four kidneys, and Evicel was injected into the tract of five kidneys. Intravenous urography (IVU) was performed on postoperative days (POD) 1 and 10 to 14. IVU was performed on two pigs at POD 30. The pigs were sacrificed and kidneys were harvested for pathologic evaluation. RESULTS: Two (20%) control kidneys had a urine leak on IVU on POD 1. None of the kidneys treated with HGM or FS had a urine leak on POD 1. None of the kidneys had a leak on POD 10 to 14 or POD 30. On pathologic inspection, the tracts of all the control kidneys and HGM kidneys had closed completely at POD 14. Two kidneys treated with FS had fistula at POD 6 and POD 14. At POD 30, the tracts in the control kidneys and kidney treated with HGM had completely healed. Fibrin sealant remained in the tract at POD 30. CONCLUSION: Fibrin sealant should be used with caution because it can persist in the tract for up to 30 days and may inhibit wound healing. Hemostatic gelatin matrix is the preferable agent because the tract closed by POD 10 to 14, similar to the findings in the control animals. The use of hemostatic agents in a nephroscopy tract may reduce the risk of early urine leak after tubeless PCNL.

Surgical steps that elongate operative time in robot-assisted radical prostatectomy among the obese population.

INTRODUCTION: The association between increased body mass index (BMI) and prolonged operative time (OT) in robot-assisted laparoscopic radical prostatectomy (RLRP) has been suggested before. It is unclear, however, which RLRP step contributes to this finding. We aimed to assess the association between BMI and duration of RLRP steps. PATIENTS AND METHODS: Records of patients who underwent RLRP between 2003 and 2009 were reviewed retrospectively. Demographics (including BMI) and OT were recorded. We reviewed total OT (incision to closure) and separate duration of sequential steps of RLRP: In room to incision (preparation), incision to robot docking (port-placement), docking to endopelvic fascia dissection end (retroperitoneal space development), dorsal vein complex (DVC) control, DVC-control end to prostate detachment (prostate dissection), vesicourethral anastomosis (anastomosis), and undocking time (undocking). We divided this cohort into BMI groups (<25, 25.0 to 29.9, 30.0 to 34.9, and ≥35) and compared their characteristics and OT. RESULTS: A total of 555 patients were analyzed. OT was significantly different across BMI groups with medians of 159, 181, 178, and 191 minutes for BMI <25, 25 to 29.9, 30 to 34.9, and ≥35 kg/m2, respectively (P = 0.002). For BMI <25, preparation and prostate dissection were significantly shorter. There was a correlation between higher BMI and longer time of prostate dissection with nerve-sparing technique (P = 0.016), but not with a non-nerve-sparing approach (P = 0.658). Higher BMI was associated with longer times of DVC-control and vesicourethral anastomosis (P = 0.048 and P = 0.035, respectively). CONCLUSIONS: Higher BMI is significantly associated with prolonged total OT for RLRP with specific steps (preparation, nerve-sparing dissection, DVC-control, anastomosis) responsible for this result. These data need to be considered when planning RLRP in the obese population.

Reduced radiation exposure with the use of an air retrograde pyelogram during fluoroscopic access for percutaneous nephrolithotomy.

INTRODUCTION: Fluoroscopy with retrograde pyelogram is commonly used to obtain access for percutaneous nephrolithotomy (PNL). Our practice uses room air for retrograde identification of calyceal anatomy. Herein we explore whether an air pyelogram was associated with a decrease in radiation exposure compared with standard retrograde pyelogram. METHODS: We retrospectively reviewed all PNL procedures performed at our institution over the past 2 years. Of the 260 PNL procedures performed during the study period, 96 had information on radiation dosage required for analysis. The effective dose (ED) was calculated using accepted conversion tables. Multivariable linear regression was used to determine the association between ED and the use of air pyelogram controlling for factors thought to affect radiation exposure. RESULTS: Of the 96 PNL procedures included in the study, 60 (63%) were performed with an air retrograde pyelogram (AP) and 36 (37%) used contrast retrograde pyelogram (CP). Both groups were matched in terms of age, body mass index, stone burden, and number of access tracts. Multivariable linear regression showed significantly lower radiation exposure in the AP group than in the CP group (p = 0.001). There was no difference in fluoroscopy time between the two groups. Using an AP lowered the mean adjusted ED nearly twofold, from 7.67 (CI = 5.99-9.81) to 4.45 (CI = 3.68-5.38) mSv. CONCLUSIONS: An air retrograde pyelogram is associated with decreased radiation exposure during PNL when compared with a contrast retrograde pyelogram.

Predictors of prolonged operative time during robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To determine risk factors for prolonged operative time (OT) during robot-assisted laparoscopic radical prostatectomy (RALP). Being able to predict prolonged OT is of pivotal importance both to the physician for patient counseling and to the hospital management. PATIENTS AND METHODS: Retrospective review of patient records undergoing RALP between 2003 and 2009 at a tertiary academic center with a structured teaching program. The following variables were recorded: age, race, body-mass index (BMI), previous abdominal surgery (yes/no), nerve-sparing technique (yes/no), lymph nodes dissection (yes/no), pathological stage (organ-confined versus non), cumulative surgical experience with RALP (expressed as number of years since introduction of RALP at our center), prostate weight and OT calculated skin-to-skin by the anesthesiologists. Prolonged OT was defined as the upper quintile (20%) according to the distribution. Multivariate regression model was generated to assess potential predictors of prolonged OT. RESULTS: A total of 523 records were retrieved. Caucasians accounted for 77.8% of the cohort. Median age was 60.3 years (interquartile range, IQR, 55.0-64.6 years), median BMI 28.1 (25.8-30.7 kg/m²), prostate weight 46.0 g (37.0-57.8 g). Eighty-six (16.4%) patients had previous abdominal surgery, lymph nodes dissection was performed in 341 (65.2%) and nerve-sparing technique was done in 310 (59.3%) cases. Median OT was 175 min (IQR 146-220 min). Prolonged OT was set at > 230 min, thereby 105 (20.1%) records were classified as such. On multivariate analysis, cumulative surgical experience with RALP (P < 0.001), nerve sparing (P = 0.023) and prostate weight (P < 0.001) were independent predictors of prolonged OT. CONCLUSIONS: Larger prostates are associated with longer OT and this effect is maintained independently of cumulative robotic experience that represents another independent factor in determining OT.

Factors affecting patient radiation exposure during percutaneous nephrolithotomy.

PURPOSE: We identified patient and stone characteristics that may contribute to increased radiation exposure during percutaneous nephrolithotomy and offer technique modifications to limit the radiation dose. MATERIAL AND METHODS: We reviewed the records of 96 patients who underwent percutaneous nephrolithotomy in the last 2 years. The effective radiation dose was calculated using accepted conversion tables. We performed multivariate linear regression to determine the association of the effective radiation dose with specific patient, stone and procedural characteristics. RESULTS: Mean±SD patient age was 51.5±13.4 years and 62.5% of the patients were female. Median body mass index was 32.0±9.7 kg/m2 (range 16.2 to 59.6) and the median stone burden was 4 cm2. Increased body mass index (p<0.001), higher stone burden (p=0.013), stone nonbranched configuration (p=0.002) and a greater number of percutaneous access tracts (p=0.040) were significantly associated with an increased effective radiation dose. Specifically obese patients with a body mass index of 30 to 39.9 kg/m2 had a more than 2-fold increase in the mean adjusted effective radiation dose and morbidly obese patients with a body mass index of 40 kg/m2 or greater had a greater than 3-fold increase vs that in normal weight patients with a body mass index of less than 25 kg/m2 (6.49 and 9.13 mSv, respectively, vs 2.66, p<0.001). Other stone specific parameters, including site and composition, percutaneous access site and estimated blood loss were not associated with the effective radiation dose. CONCLUSIONS: Patients with higher body mass index, greater stone burden, nonbranched stones and multiple nephrostomy access tracts are at risk for increased radiation exposure during percutaneous nephrolithotomy. Urologists must seek alternative strategies to minimize radiation exposure, such as tighter collimation to the region of interest, judicious use of magnification and the acquisition of as few images as possible during stone removal.

Endopyelotomy in the age of laparoscopic and robotic-assisted pyeloplasty.

Ureteropelvic junction obstructixon (UPJO) management has undergone significant changes in the past few years. The aim of this review is to establish the role of endopyelotomy in the age of laparoscopic and robot-assisted laparoscopic pyeloplasty (RALP). Open pyeloplasty (OP) has been the gold standard of care for UPJO for the past six decades. Due to lower long-term efficacy, endopyelotomy has failed to replace OP. However, laparoscopic pyeloplasty (LP) has been able to reproduce the high success rates of OP, while also achieving minimal morbidity. Unfortunately, the steep learning curve and technical difficulties have hindered its use. Recently, robot-assisted systems have enabled LP to overcome its disadvantages, and this may render endopyelotomy obsolete. Although LP and RALP are emerging as the gold standard of treatment for UPJO, endopyelotomy could carve out a niche area as a salvage procedure. Endopyelotomy will continue to have a role in the management of UPJO, albeit a smaller one.

The impact of societal changes on patterns of urolithiasis.

PURPOSE OF REVIEW: The purpose of the present review is to track changes in prevalence and composition of stone disease as a result of lifestyle changes over the past century. RECENT FINDINGS: Increasing rates of obesity, diabetes mellitus and metabolic syndrome have resulted in increasing rates of nephrolithiasis among women, decreasing the male-to-female ratio from 1.3: 1 to 1.7: 1. Urine composition results have revealed a decrease in urinary pH (<5.5) and an increase in urinary uric acid supersaturation. This has resulted in increased rates of uric acid stones. Modern bariatric surgeries have further increased the risk of calcium oxalate stone formation. Offending agents, intentionally or unintentionally added to food or drug products, have also led to the appearance of previously unrecognized stone types, that is, melamine and indinavir calculi. SUMMARY: Societal changes have had a tremendous impact on stone prevalence and composition. Prompt healthier lifestyle education as well as tighter quality control in the Food and Drug Industry is paramount to reducing nephrolithiasis rates and its complications.