Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic.

BACKGROUND: Renal colic is acute pain caused by urinary stones. The prevalence of urinary stones is between 10% and 15% in the United States, making renal colic one of the common reasons for urgent urological care. The pain is usually severe and the first step in the management is adequate analgesia. Many different classes of medications have been used in this regard including non-steroidal anti-inflammatory drugs and narcotics. OBJECTIVES: The aim of this review was to assess benefits and harms of different NSAIDs and non-opioids in the treatment of adult patients with acute renal colic and if possible to determine which medication (or class of medications) are more appropriate for this purpose. Clinically relevant outcomes such as efficacy of pain relief, time to pain relief, recurrence of pain, need for rescue medication and side effects were explored. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register (to 27 November 2014) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: Only randomised or quasi randomised studies were included. Other inclusion criteria included adult patients with a clinical diagnosis of renal colic due to urolithiasis, at least one treatment arm included a non-narcotic analgesic compared to placebo or another non-narcotic drug, and reporting of pain outcome or medication adverse effect. Patient-rated pain by a validated tool, time to relief, need for rescue medication and pain recurrence constituted the outcomes of interest. Any adverse effects (minor or major) reported in the studies were included. DATA COLLECTION AND ANALYSIS: Abstracts were reviewed by at least two authors independently. Papers meeting the inclusion criteria were fully reviewed and relevant data were recorded in a standardized Cochrane Renal Group data collection form. For dichotomous outcomes relative risks and 95% confidence intervals were calculated. For continuous outcomes the weighted mean difference was estimated. Both fixed and random models were used for meta-analysis. We assessed the analgesic effects using four different outcome variables: patient-reported pain relief using a visual analogue scale (VAS); proportion of patients with at least 50% reduction in pain; need for rescue medication; and pain recurrence. Heterogeneity was assessed using the I² test. MAIN RESULTS: A total of 50 studies (5734 participants) were included in this review and 37 studies (4483 participants) contributed to our meta-analyses. Selection bias was low in 34% of the studies or unclear in 66%; performance bias was low in 74%, high in 14% and unclear in 12%; attrition bias was low in 82% and high in 18%; selective reporting bias low in 92% of the studies; and other biases (industry funding) was high in 4%, unclear in 18% and low in 78%.Patient-reported pain (VAS) results varied widely with high heterogeneity observed. For those comparisons which could be pooled we observed the following: NSAIDs significantly reduced pain compared to antispasmodics (5 studies, 303 participants: MD -12.97, 95% CI -21.80 to - 4.14; I² = 74%) and combination therapy of NSAIDs plus antispasmodics was significantly more effective in pain control than NSAID alone (2 studies, 310 participants: MD -1.99, 95% CI -2.58 to -1.40; I² = 0%).NSAIDs were significantly more effective than placebo in reducing pain by 50% within the first hour (3 studies, 197 participants: RR 2.28, 95% CI 1.47 to 3.51; I² = 15%). Indomethacin was found to be less effective than other NSAIDs (4 studies, 412 participants: RR 1.27, 95% CI 1.01 to 1.60; I² = 55%). NSAIDs were significantly more effective than hyoscine in pain reduction (5 comparisons, 196 participants: RR 2.44, 95% CI 1.61 to 3.70; I² = 28%). The combination of NSAIDs and antispasmodics was not superior to NSAIDs only (9 comparisons, 906 participants: RR 1.00, 95% CI 0.89 to 1.13; I² = 59%). The results were mixed when NSAIDs were compared to other non-opioid medications.When the need for rescue medication was evaluated, Patients receiving NSAIDs were significantly less likely to require rescue medicine than those receiving placebo (4 comparisons, 180 participants: RR 0.35, 95% CI 0.20 to 0.60; I² = 24%) and NSAIDs were more effective than antispasmodics (4 studies, 299 participants: RR 0.34, 95% CI 0.14 to 0.84; I² = 65%). Combination of NSAIDs and antispasmodics was not superior to NSAIDs (7 comparisons, 589 participants: RR 0.99, 95% CI 0.62 to 1.57; I² = 10%). Indomethacin was less effective than other NSAIDs (4 studies, 517 participants: RR 1.36, 95% CI 0.96 to 1.94; I² = 14%) except for lysine acetyl salicylate (RR 0.15, 95% CI 0.04 to 0.65).Pain recurrence was reported by only three studies which could not be pooled: a higher proportion of patients treated with 75 mg diclofenac (IM) showed pain recurrence in the first 24 hours of follow-up compared to those treated with 40 mg piroxicam (IM) (60 participants: RR 0.05, 95% CI 0.00 to 0.81); no significant difference in pain recurrence at 72 hours was observed between piroxicam plus phloroglucinol and piroxicam plus placebo groups (253 participants: RR 2.52, 95% CI 0.15 to12.75); and there was no significant difference in pain recurrence within 72 hours of discharge between IM piroxicam and IV paracetamol (82 participants: RR 1.00, 95% CI 0.65 to 1.54).Side effects were presented inconsistently, but no major events were reported. AUTHORS' CONCLUSIONS: Although due to variability in studies (inclusion criteria, outcome variables and interventions) and the evidence is not of highest quality, we still believe that NSAIDs are an effective treatment for renal colic when compared to placebo or antispasmodics. The addition of antispasmodics to NSAIDS does not result in better pain control. Data on other types of non-opioid, non-NSAID medication was scarce.Major adverse effects are not reported in the literature for the use of NSAIDs for treatment of renal colic.

Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration.

Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34(+) hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34(+) grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

Utilization of computer enhanced visual learning (CEVL) method improves endoscopic diagnosis of posterior urethral valves (PUV).

INTRODUCTION: Training in urology relies largely on the traditional methods of clinical immersion and the use of reference texts. Computer enhanced visual learning (CEVL) is an on-line learning tool that may effectively supplement these methods. We evaluate the role of CEVL in establishing the endoscopic diagnosis of posterior urethral valves (PUV). MATERIAL AND METHODS: This study compares test scores of PUV diagnosis made by pediatric urologists and fellows in pediatric urology training programs while watching pediatric cystourethroscopy videos before and after viewing the CEVL learning module. The CEVL module used illustrations and video clips to highlight criteria important in diagnosing PUV. Data was analyzed for improvement in test scores (Chi square). RESULTS: There were 112 study subjects enrolled. An improvement in the post-test scores was observed (p < 0.001). When independently analyzing cases with PUV, an improvement in diagnosis was also observed (p < 0.005). While a trend toward improvement was observed in correctly diagnosing normal urethras, this was not statistically significant. CONCLUSION: Overall, there was an improvement observed after viewing the CEVL module. This was most notable in cases where PUV was present. The CEVL module is an effective supplement for enhancing the endoscopic diagnosis of PUV.

A nonhuman primate model for urinary bladder regeneration using autologous sources of bone marrow-derived mesenchymal stem cells.

Animal models that have been used to examine the regenerative capacity of cell-seeded scaffolds in a urinary bladder augmentation model have ultimately translated poorly in the clinical setting. This may be due to a number of factors including cell types used for regeneration and anatomical/physiological differences between lower primate species and their human counterparts. We postulated that mesenchymal stem cells (MSCs) could provide a cell source for partial bladder regeneration in a newly described nonhuman primate bladder (baboon) augmentation model. Cell-sorted CD105(+) /CD73(+) /CD34(-) /CD45(-) baboon MSCs transduced with green fluorescent protein (GFP) were seeded onto small intestinal submucosa (SIS) scaffolds. Baboons underwent an approximate 40%-50% cystectomy followed by augmentation cystoplasty with the aforementioned scaffolds or controls and finally enveloped with omentum. Bladders from sham, unseeded SIS, and MSC/SIS scaffolds were subjected to trichrome, H&E, and immunofluorescent staining 10 weeks postaugmentation. Immunofluorescence staining for muscle markers combined with an anti-GFP antibody revealed that >90% of the cells were GFP(+) /muscle marker(+) and >70% were GFP(+) /Ki-67(+) demonstrating grafted cells were present and actively proliferating within the grafted region. Trichrome staining of MSC/SIS-augmented bladders exhibited typical bladder architecture and quantitative morphometry analyses revealed an approximate 32% and 52% muscle to collagen ratio in unseeded versus seeded animals, respectively. H&E staining revealed a lack of infiltration of inflammatory cells in grafted animals and in corresponding kidneys and ureters. Simple cystometry indicated recovery between 28% and 40% of native bladder capacity. Data demonstrate MSC/SIS composites support regeneration of bladder tissue and validate this new bladder augmentation model.

Holmium:yttrium-aluminum-garnet lithotripsy proximal fiber failures from laser and fiber mismatch.

OBJECTIVES: To document proximal fiber failures at the subminiature version A connector during holmium:yttrium-aluminum-garnet lithotripsy when fibers and lasers are mismatched. METHODS: Optical fibers supplied by Trimedyne were coupled to holmium:yttrium-aluminum-garnet lasers from Lumenis (VersaPulse 100 W), New Star (NS1500 12 W), and Dornier (Medilas H20) for an in vitro experiment. We reviewed the operating room laser log for our Lumenis VersaPulse 100 W laser for an in vivo experiment. The lasers were maintained with the rods aligned. The use of a different brand, small caliber (diameter less than 300 microm) and larger fibers and the number of proximal fiber failures were recorded. RESULTS: The in vitro experiment was stopped prematurely because the fiber failed on the New Star laser with an audible explosion sound and smoke emanating from the connector end. The fiber could not be extracted from the laser. The fiber at its connector end had melted and fused to the laser terminal. In vivo, 4% of all cases using the sub-300-microm fibers had connector end failures versus 0% of 365-microm fibers, and 0% of 550-microm fibers (P <0.001). Of 188 consecutive cases using the sub-300-microm fibers, 4 (13%) of 30 cases had connector end failures using the Trimedyne fiber versus 3 (2%) of 155 cases using the Lumenis fiber (P <0.01). CONCLUSIONS: The mismatch of small-caliber fibers with lasers runs the risk of fiber failure, energy reflected back at the laser, and laser damage. Urologists should familiarize themselves with the specifications of their holmium:yttrium-aluminum-garnet lasers and fibers to avoid expensive laser repairs.

Lasers in clinical urology: state of the art and new horizons.

We present an overview of current and emerging lasers for Urology. We begin with an overview of the Holmium:YAG laser. The Ho:YAG laser is the gold standard lithotripsy modality for endoscopic lithotripsy, and compares favorably to standard electrocautery transurethral resection of the prostate for benign prostatic hyperplasia (BPH). Available laser technologies currently being studied include the frequency doubled double-pulse Nd:Yag (FREDDY) and high-powered potassium-titanyl-phosphate (KTP) lasers. The FREDDY laser presents an affordable and safe option for intracorporeal lithotripsy, but it does not fragment all stone compositions, and does not have soft tissue applications. The high power KTP laser shows promise in the ablative treatment of BPH. Initial experiments with the Erbium:YAG laser show it has improved efficiency of lithotripsy and more precise ablative and incisional properties compared to Ho:YAG, but the lack of adequate optical fibers limits its use in Urology. Thulium:YAG fiber lasers have also demonstrated tissue ablative and incision properties comparable to Ho:YAG. Lastly, compact size, portability, and low maintenance schedules of fiber lasers may allow them to shape the way lasers are used by urologists in the future.