Anatomical location and number of injection sites of intravesical OnabotulinumtoxinA for females with refractory idiopathic overactive bladder: A scoping review.

AIMS: The negative impact on quality of life and the economic-related burden to the patient and the health care system associated with idiopathic overactive bladder (iOAB) is well-documented. Intradetrusor OnabotulinumtoxinA (BTN/A) injections are a well-used treatment modality for the management of overactive detrusor refractory to medical management, with well-documented efficacy and safety profiles. There is currently no best practice guideline for the administration of BTN/A for this procedure and historically the trigone of the bladder has been excluded from the injection paradigm given the risk of vesicoureteral reflux (VUR). METHODS: A scoping review methodology was employed to assess available literature to evaluate current techniques used. There is emerging literature that the inclusion of the trigone may increase the efficacy of the procedure, while maintaining a similar adverse effect profile. Similar results could also be obtained by decreasing the number of injection sites. A scoping review was completed with systematic methodology using the Preferred Systematic Reviews and Meta Analyses extension for Scoping Review checklist. The search strategy looked to evaluate BTN/A and number of injection sites and the inclusion of the trigone in female patients with iOAB. Studies with male or neurogenic bladder only were excluded. Mixed studies were included. A specialist research librarian was engaged, with supervision from a functional urologist using a combination of MeSH and natural language terms. Two investigators independently reviewed the titles and abstracts. RESULTS: Twelve articles were included and were published between 2005 and 2021. There was no evidence of VUR in any of the results. All but one study reported similar if not improved efficacy of trigone-inclusion. Lower number of injection sites had similar efficacy profiles to higher numbers of intradetrusor injections. CONCLUSIONS: Further high-quality randomized control trials of trigone inclusion and reduction of injection sites are required. It is hoped that with further exploration of intraoperative methods for BTN/A injections, the development of universally accepted guidelines may optimize management and experiences for patients with iOAB.

Macrocystic ductal adenocarcinoma, a good outcome for a rare cancer in an elderly comorbid patient.

Ductal adenocarcinoma is an aggressive prostate cancer often presenting late due to low serum PSA. A variant presentation of ductal adenocarcinoma occurs with formation of large cystic structures in the prostate, often associated with lower urinary tract symptoms. We present a case illustrating investigation and successful management of a macrocytic ductal carcinoma in a 90 year old patient.

Are we underestimating urinary retention following intravesical onabotulinumtoxinA in women with overactive bladder and a history of prior pelvic surgery?

AIMS: This study's purpose is to review the rates of urinary retention requiring intermittent catheterization (IC) post intravesical OnabotulinumtoxinA (BTN/A) injection for idiopathic overactive bladder from a single practicing specialist urological surgeon. METHODS: We performed a retrospective review of a single Australian urologist to identify the rate of intermittent catheterization in our clinical setting. Logistic regression was used to assess associations between requirement of IC and risk factors for urinary retention. RESULTS: Ninety-four patients were included after inclusion and exclusion criteria were applied and the average age was 69.7 years (SD 17.2) and all participants were female. Thirty-six percent (n = 34) of patients required IC. Of patients requiring IC, 32% had a prior urethral sling, 35% had prior vaginal prolapse surgery, and 29% had a preoperative urinary tract infection (UTI). There was strong evidence of univariate associations between IC and prior sling (odds ratio [OR]: 5.26, 95% confidence interval [CI]: 1.64-16.55, p = 0.005), preoperative UTI (OR: 4.25, 95% CI: 1.31-13.08, p = 0.016) and prior vaginal prolapse surgery (OR: 4.91, 95% CI: 1.64-14.72, p = 0.005). Evidence that prior sling patients were more likely to require IC remained strong in a multivariable model (OR: 7.35, 95% CI: 1.59-34.11, p = 0.011). CONCLUSION: Prior urethral sling surgery, prior vaginal prolapse surgery, and positive preoperative UTI, despite treatment, were found to be associated with a higher rate of initiation of intermittent catheterization. The rate of IC initiation of 36% was higher than reported in prior clinical trials.

Clinical Utility of a Single-Use Flexible Cystoscope Compared with a Standard Reusable Device: A Randomized Noninferiority Study.

Objective: A noninferiority assessment of single-use digital flexible cystoscopy (FC) compared with standard reusable FC for bladder cancer surveillance, and investigation of lower urinary tract symptoms. Patients and Methods: Patients requiring FC who met inclusion criteria were randomly assigned to have their procedure performed using a single-use cystoscope (Ambu® aScope™ 4 Cysto System) or a standard reusable cystoscope (Olympus CYF-VH flexible video cystoscope). Primary outcomes were noninferiority of the single-use cystoscope, in terms of effective procedure completion rate, image quality, light quality, and maneuverability. Secondary objectives compared safety, operative, and perioperative time. The noninferiority margin was set at -10%. Results: One hundred one patients completed the study (n = 50 trial, n = 51 control). All primary outcomes demonstrated noninferiority of the single-use cystoscope, compared with standard reusable FC. Effective completion rate, image quality, light quality, and maneuverability between single-use and reusable cystoscopes were 100% and 98% (confidence interval [CI]: -0.059 to 0.019); 96% and 100% (CI: -0.014 to 0.092); 98% and 100% (CI: -0.018 to 0.058); and 98% and 100% (CI: -0.018 to 0.058). There was no difference in operation time (p = 0.415) or total theater use time (p = 0.441) between groups. Adverse event rates were 4.08% and 4.16% in the trial group and control groups, respectively. Conclusion: The single-use Ambu flexible cystoscope is noninferior to standard FC in terms of procedure completion and light quality, image quality, and maneuverability. Single-use flexible cystoscopes are an effective and safe alternative to reusable flexible cystoscopes and may act as a suitable alternative or adjunct in the urologist's armamentarium.

Intraoperative indocyanine green fluorescence navigation in a robot-assisted partial nephrectomy for a large renal cell carcinoma in a horseshoe kidney.

A man in his 60s was referred to the urology department with an incidental finding of large 75 mm mass within a horseshoe kidney. CT imaging highlighted the well-known aberrant arterial anatomy seen in horseshoe kidney which often causes significant surgical challenges.After careful preoperative planning, the mass was resected successfully during a robot-assisted partial nephrectomy. Intraoperatively, indocyanine green fluorescence navigation helped to confirm arteries supplying area of resection were appropriately clamped, allowing for safe resection of the mass. Histology revealed a chromophobe renal cell carcinoma with clear margins. The patient was discharged on day 4 postoperatively and continues to be cancer free on routine surveillance imaging.

Case report: Recurrent urethral polyps, an atypical presentation of ductal prostate adenocarcinoma.

Prostate ductal adenocarcinoma is a rare subtype of prostate adenocarcinoma which can show aggressive features and have poor response to conventional treatment. Early diagnosis aids in shared patient decision making. We report an atypical presentation of this rare condition where a recurrent urethral polyp which showed pagetoid spread was diagnosed as ductal adenocarcinoma of the prostate, with emphasis on review of prior available histology.

Optimizing surgical training in the time of COVID-19-Victorian regional teaching hospital experience.

BACKGROUND: Reductions in elective surgery due to the COVID-19 pandemic led to a paralleled reduction in patient based surgical training opportunities. METHODS: To quantify the impact of COVID-19 on surgical training, we completed a retrospective audit of the Urology Department activity during Victorian pandemic waves in 2020 at our large regional teaching hospital. Corresponding weeks in the year prior were used as the control. Interviews with department members illustrated the adaptive approach to surgical training used at our institution. RESULTS: A State of Disaster Surgical Triage Team was assembled and surgical operations were split between one public and two private hospitals. A pandemic triaging protocol was established and 335 Category-2 patients were re-triaged. The first wave saw a 13.8% reduction in clinic reviews, with the second wave having an overall increase of 8.8% with 56% being telehealth. The second wave saw an 11.0% reduction in overall operating, with reduced emergency operating in both the first and second wave of 17.4% and 45.5%, respectively. Reductions impacted surgical technical skill training, resulting in surgical education provided through technology platforms including webinars, podcasts and pre-recorded operative videos. The unique challenges trainees were faced with due to the pandemic encouraged development of non-technical RACS competencies. CONCLUSION: The COVID-19 pandemic presented significant challenges for service delivery and training. Reduced direct patient contact and procedures, but opportunities to develop the non-technical skills required to respond to the pandemic. The use of variable educational opportunities and tools ensured our trainees continued to progress through their training.

Case report: Challenging adult case of erosive coronal sulcus hair thread tourniquet.

Hair thread tourniquet syndrome has been well described in the literature, with one of the rare presentations including resultant tourniquet of the penis. We describe an unusual case in an adult resulting in erosion of the urethra as well as the reconstructive and social challenges faced in an attempt to preserve the glans. SECTION HEADING: Trauma and Reconstruction.

Amygdala selectively modulates defensive responses evoked from the superior colliculus in non-human primates.

Brain circuitry underlying defensive behaviors includes forebrain modulatory sites, e.g. the amygdala and hypothalamus, and midbrain effector regions, such as the deep/intermediate layers of the superior colliculus (DLSC). When disinhibited, this network biases behavior towards reflexive defense reactions. While well characterized in rodent models, little is known about this system in the primate brain. Employing focal pharmacological manipulations, we have previously shown that activation of the DLSC triggers reflexive defensive responses, including cowering, escape behaviors and defensive vocalizations. Here, we show that activation of the DLSC also disrupts normal dyadic social interactions between familiar pairs of monkeys. When the basolateral complex of the amygdala (BLA) was inhibited concurrent with DLSC activation, cowering behavior was attenuated, whereas escape behaviors and defensive vocalizations were not. Moreover, inhibition of the BLA, previously shown to produce a profound increase in dyadic social interactions, was unable to normalize the decrease in social behavior resulting from DLSC activation. Together these data provide an understanding of forebrain-midbrain interactions in a species and circuit with translational relevance for the psychiatry of anxiety and post-traumatic stress disorders.

Defense-like behaviors evoked by pharmacological disinhibition of the superior colliculus in the primate.

Stimulation of the intermediate and deep layers of superior colliculus (DLSC) in rodents evokes both orienting/pursuit (approach) and avoidance/flight (defense) responses (Dean et al., 1989). These two classes of response are subserved by distinct output projections associated with lateral (approach) and medial (defense) DLSC (Comoli et al., 2012). In non-human primates, DLSC has been examined only with respect to orienting/approach behaviors, especially eye movements, and defense-like behaviors have not been reported. Here we examined the profile of behavioral responses evoked by activation of DLSC by unilateral intracerebral infusions of the GABA(A) receptor antagonist, bicuculline methiodide (BIC), in nine freely moving macaques. Across animals, the most consistently evoked behavior was cowering (all animals), followed by increased vocalization and escape-like behaviors (seven animals), and attack of objects (three animals). The effects of BIC were dose-dependent within the range 2.5-14 nmol (threshold dose of 4.6 nmol). The behaviors and their latencies to onset did not vary across different infusion sites within DLSC. Cowering and escape-like behaviors resembled the defense-like responses reported after DLSC stimulation in rats, but in the macaques these responses were evoked from both medial and lateral sites within DLSC. Our findings are unexpected in the context of an earlier theoretical perspective (Dean et al., 1989) that emphasized a preferential role of the primate DLSC for approach rather than defensive responses. Our data provide the first evidence for induction of defense-like behaviors by activation of DLSC in monkeys, suggesting that the role of DLSC in responding to threats is conserved across species.

Topography of dyskinesias and torticollis evoked by inhibition of substantia nigra pars reticulata.

GABAergic neurons of the substantia nigra pars reticulata (SNpr) and globus pallidus pars interna (GPi) constitute the output pathways of the basal ganglia. In monkeys, choreiform limb dyskinesias have been described after inhibition of the GPi, but not the SNpr. Given the anatomical and functional similarities between these structures, we hypothesized that choreiform dyskinesias could be evoked by inhibition of an appropriate region within the SNpr. The GABAA receptor agonist, muscimol, was infused into various sites within the SNpr and the adjacent STN of freely moving macaques. The effect of the GABAA antagonist, bicuculline (BIC), was also examined. Muscimol (MUS) in SNpr evoked the following: (1) choreiform dyskinesias of the contralateral arm and/or leg from central and lateral sites; (2) contralaterally directed torticollis from central and posterior sites; and (3) contraversive quadrupedal rotation from anterior and lateral sites. MUS infusions into the adjacent SN pars compacta or STN were without effect, ruling out a contribution of drug spread to adjacent structures. BIC in SNpr induced ipsiversive postures without choreiform dyskinesia or torticollis, whereas in the STN, it evoked ballistic movements. This is the first report of choreiform dyskinesia evoked by inhibition of the SNpr. This highly site-specific effect was obtained from a restricted region within the SNpr distinct from that responsible for inducing torticollis. These results suggest that overactivity of different SNpr outputs mediates choreiform dyskinesia and torticollis. These abnormalities are symptoms of dystonia, Huntington's disease, and iatrogenic dyskinesias, suggesting that these conditions may result, in part, from a loss of function in SNpr efferent projections.

Superior colliculus mediates cervical dystonia evoked by inhibition of the substantia nigra pars reticulata.

Cervical dystonia (CD; spasmodic torticollis) can be evoked by inhibition of substantia nigra pars reticulata (SNpr) in the nonhuman primate (Burbaud et al., 1998; Dybdal et al., 2012). Suppression of GABAergic neurons that project from SNpr results in the disinhibition of the targets to which these neurons project. It therefore should be possible to prevent CD by inhibition of the appropriate nigral target region(s). Here we tested the hypothesis that the deep and intermediate layers of the superior colliculus (DLSC), a key target of nigral projections, are required for the emergence of CD. To test this hypothesis, we pretreated the DLSC of four macaques with the GABA(A) agonist muscimol to determine whether this treatment would prevent CD evoked by muscimol infusions in SNpr. Our data supported this hypothesis: inhibition of DLSC attenuated CD evoked by muscimol in SNpr in all four animals. In two of the four subjects, quadrupedal rotations were evoked by muscimol application into SNpr sites that were distinct from those that induced dystonia. We found that inhibition of DLSC did not significantly alter quadrupedal rotations, suggesting that this response is dissociable from the SNpr-evoked CD. Our results are the first to demonstrate a role of DLSC in mediating the expression of CD. Furthermore, these data reveal a functional relationship between SNpr and DLSC in regulating posture and movement in the nonhuman primate, raising the possibility that the nigrotectal pathway has potential as a target for therapeutic interventions for CD.

Hydroxybutyrate near-patient testing to evaluate a new end-point for intravenous insulin therapy in the treatment of diabetic ketoacidosis in children.

BACKGROUND: The aim of this study was to assess the clinical application of a near-patient testing (NPT) device for capillary blood hydroxybutyrate (HOB) measurement in evaluating a new end-point for intravenous insulin therapy in the treatment of diabetic ketoacidosis (DKA) in children. METHODS: Children fulfilling the criteria for DKA were treated according to an integrated care pathway (ICP) with fluid replacement and insulin infusion. We measured capillary HOB hourly by NPT (Abbott Optium meter, analytical range 0-6.0 mmol/L), venous blood gases 4 hourly, and venous HOB 4 hourly by laboratory enzymatic method and tested all urine passed for ketones. Two possible ICP end-points were compared: A, pH > 7.3 followed by two successive NPT HOB measurements <1 mmol/L, and B, pH > 7.3 and urine ketone free (our current end-point). RESULTS: In 35 patient episodes, the ICP was completed (28 to negative ketonuria) without significant variation. Before treatment, median (range) laboratory HOB was 9.5 mmol/L (4.6-15.70 mmol/L), pH 7.18 (6.98-7.38), and standard bicarbonate 11.5 mmol/L (4.3-18.6 mmol/L). ICP end-point A was reached after 17 h (4-39 h), whereas end-point B was not reached until 28 h (14-64 h) after starting treatment. The median lag was 11 h (1-36 h). For 59 paired venous samples (excluding samples with laboratory HOB >6 mmol/L), the relation between NPT (y) and laboratory (x) HOB was y = 0.92x - 0.05, r(2)= 0.94, mean bias -0.25 mmol/L. CONCLUSIONS: (i) Serial measurement of NPT HOB allows evaluation of a new, simple, earlier end-point for intravenous insulin therapy. (ii) Agreement between NPT and laboratory HOB was clinically acceptable for HOB levels within the meter's analytical range.

Mutations in the extra sex combs and Enhancer of Polycomb genes increase homologous recombination in somatic cells of Drosophila melanogaster.

We found that heterozygous mutant alleles of E(Pc) and esc increased homologous recombination from an allelic template in somatic cells in a P-element-induced double-strand break repair assay. Flies heterozygous for mutant alleles of these genes showed increased genome stability and decreased levels of apoptosis in imaginal discs and a concomitant increase in survival following ionizing radiation. We propose that this was caused by a genomewide increase in homologous recombination in somatic cells. A double mutant of E(Pc) and esc had no additive effect, showing that these genes act in the same pathway. Finally, we found that a heterozygous deficiency for the histone deacetylase, Rpd3, masked the radiation-resistant phenotype of both esc and E(Pc) mutants. These findings provide evidence for a gene dosage-dependent interaction between the esc/E(z) complex and the Tip60 histone acetyltransferase complex. We propose that esc and E(Pc) mutants enhance homologous recombination by modulating the histone acetylation status of histone H4 at the double-strand break.