Management of the refractory nocturnal enuresis patient to desmopressin in a pediatric population: Desmopressin + oxybutynin vs. desmopressin + imipramine.

INTRODUCTION AND OBJECTIVE: Desmopressin is well accepted as first-line medical therapy for enuresis. If ineffective, combination therapy of desmopressin + oxybutynin or desmopressin + imipramine has been used. This study assessed the efficacy of adjunct therapy with either imipramine or oxybutynin in the management of enuresis patients who failed desmopressin treatment. STUDY DESIGN: A retrospective chart review of our database for patients with enuresis was performed. Patients who were prescribed desmopressin, oxybutynin, and imipramine over 14 years for enuresis were included. Two cohorts of patients were examined; group OXY was treated with desmopressin and oxybutynin, and group IMP received desmopressin and imipramine. Pretreatment measurement of Vancouver Symptom Scores (VSS) were used to compare groups using the VSS question "I wet my bed at night" where 4: every night, 3: 4-5 nights per week, 2: 1-2 nights per week, 1: 3-4 nights per month, and 0: never. International Children's Continence Society (ICCS) criteria for continence success was utilized to determine outcomes. RESULTS: 2521 patients prescribed one of the 3 medications were identified. Among them, 81 patients (mean age: 10.5 ± 2.8 years) received combination therapy. Of which, 55 were male and 26 female. Specifically, 58 were prescribed both desmopressin and imipramine (group IMP), 23 desmopressin and oxybutynin (group OXY), and 4 transitioned from OXY to IMP. Mean pretreatment VSS showed no difference between groups. Both groups experienced minimal drops in wet nights with desmopressin alone. A comparison revealed that group IMP reduced wet nights significantly more than group OXY (VSS wet night score 0.7 ± 1.2 vs. 2.3 ± 1.1 respectively, p < 0.0001). Non-intent-to-treat complete response rate was 68% vs 5% (OR = 42.5, p < 0.001) (IMP vs. OXY respectively). Intent-to-treat response rates were 58%. DISCUSSION: Although first-line desmopressin treatment for enuresis is effective, it does not work for all patients, and many parents and children desire nighttime dryness. Clinicians have combined desmopressin with oxybutynin or imipramine for improved results, but research comparing these modalities is scarce. Our study suggests that the desmopressin and imipramine combination is superior at reducing nights wet compared to desmopressin and oxybutynin, attributed to imipramine's probable central mechanism rather than its secondary anticholinergic properties. Limitations include a modest sample size, retrospective design, and subjective responses to the Vancouver questionnaire. CONCLUSION: A combination of desmopressin and imipramine was more effective in reducing wet nights and had a complete response rate that was 42.5 times greater than desmopressin and oxybutynin.

Size matters: Total testicular volume predicts sperm count in Tanner V varicocele patients.

INTRODUCTION: It is known the prevalence of varicoceles in adolescent men is 14-29% but there is debate surrounding implications on fertility. As obtaining a semen analysis (SA) may be challenging, there is need for objective tests as measures of fecundity. Our aim was to investigate the relationship between testicular volume differential (TVD), varicocele grade, and total testicular volume (TTV) on seminal parameters including total motile sperm count (TMSC). MATERIALS AND METHODS: We conducted a retrospective single-center chart review over 14 years of 486 Tanner V adolescent males. Three hundred and four met inclusion of palpable, non-operated left-sided varicocele who underwent at least one SA and ultrasound. Abnormal TMSC was defined by World Health Organization 2010 criteria for minimal reference ranges. Multivariate logistic regression, receiver operating characteristic analysis with Youden J-statistic and descriptive statistics were performed. RESULTS: Three hundred and four Tanner V adolescents with median age of 18.0 years (18.0-19.0), median TTV of 34.5 cc (28.9, 40.2) and median TMSC of 62.5 million/ejaculate (25.4, 123.4) were evaluated. TTV cutoff of 29.5 cc was found to predict TMSC of <9 million/ejaculate with negative predictive value of 96.2% and odds ratio of 6.08 ([2.13-17.42], p < 0.001). TVD greater than 20% did not reach statistical significance with an odds ratio of 1.66 ([0.41-6.62], p = 0.50). DISCUSSION: In clinical practice, each patient will need to have an individualized plan. Based on our data, for older adolescents (17 or 18 years) with varicocele and an abnormal TTV, clinicians may have a lower threshold for advising SA, and if unable to obtain, surgical intervention and/or closer surveillance should be stressed. Patients should be informed of their six-fold increase in abnormal SA. Patients with normal TTV should be advised they are at lower risk of having abnormal SA. Younger patients with varicocele and an initial TVD>20%, should be followed closely but intervention delayed until 17 or 18 to better assess TTV. The importance of trending patient data should be emphasized as a single measurement has low predictive value for developing adolescents. Limitations of our study include a retrospective design and the lack of uniform correlation between adolescent SA and paternity. CONCLUSIONS: Total testicular volume less than 29.5 cc increased odds of abnormal semen analysis by over six times and had a negative predictive value of 96.2%. Ultrasound results may be useful for risk stratification and counselling on appropriateness of surgical intervention.

A comparison of 467 uroflowmetry results in repaired hypospadias vs. normal male flows.

INTRODUCTION: There are currently no clinical criteria for obstructed urinary flow after hypospadias repair surgery. Previous studies have utilized adult and pediatric nomograms and flow shapes to define obstruction, however these methods are limited by a lack of standardization and lack of interrater reliability when determining flow shapes, respectively. The idealized voider derived flow indexes offer a way to track uroflowmetry results in a volume and age agnostic manner. OBJECTIVE: We sought to evaluate all our hypospadias patients over a 10-year period and identify patients without complications and those with complications and determine their respective flow parameters. Our secondary objective is to identify which uroflowmetry parameters are the most significant predictors of urethral stricture and meatal stenosis at the time of the uroflowmetry study. STUDY DESIGN: Retrospective chart review was used to compile demographic information, details of hypospadias repair surgeries, and uroflowmetry results from pediatric hypospadias repair patients. Subjects were divided into distal, midshaft, and proximal groups based on the initial location of their urethral meatus. Flows from the hypospadias repair groups were compared to flows from normal age matched controls from a previous study. We compared flows from hypospadias repair patients with no complications present with those who had urethral stricture or meatal stenosis present at the time of uroflowmetry. Binary logistic regression and ROC analysis was used to assess different uroflowmetry parameters' ability to detect the presence of obstructed urine flow. RESULTS: 467 uroflowmetry studies from 200 hypospadias repair patients were included in the database. Compared to controls, the hypospadias repair groups tended to have significantly lower Qmax, Qavg, Qmax FI, Qavg FI, and longer ttQmax. Significant differences in flow parameters were observed when comparing hypospadias repair patients with and without flow obstructing complications at the time of uroflowmetry. Binary logistic regression including various uroflowmetry parameters showed Qmax FI had a significant effect on the odds of observing the absence of a stricture in proximal and distal hypospadias cases. DISCUSSION: Of the uroflowmetry parameters analyzed, binary logistic regression and the likelihood ratio of a positive result all point to Qmax FI as the better parameter to use to detect the presence of complications in patients who have undergone distal or proximal hypospadias repair surgery. CONCLUSION: We have established normal parameters for post-operative hypospadias repair patients which can be used to follow patients over time and allow for the identification of complications by keeping track of flow indexes which are volume and age agnostic.

Prevalence of Sleep CALM nocturia factors in a male veteran population.

INTRODUCTION: Nocturia is a complex and multifactorial condition, associated with several genitourinary abnormalities as well as a host of conditions beyond the urinary tract, and thus often poses a significant diagnostic challenge in real-world practice. Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications, the so-called "Sleep C.A.L.M." factors, are five common causes of nocturia requiring judicious evaluation according to current consensus guidelines. This study aims to assess the prevalence of the Sleep C.A.L.M. factors in a nocturia clinical population. METHODS: Retrospective analysis of frequency-volume charts from men with ≥2 nocturnal voids as well as concurrent demographic, clinical, and medical history data to identify patients with each of the Sleep C.A.L.M. FACTORS: Comorbidities and medications were classified as a single group. RESULTS: A total of 213 subjects met the criteria for inclusion (median age 68.0 [63.5-75.5] years). The prevalence of 1) sleep disorders, 2) comorbidities and/or medication use, 3) actions (i.e., modifiable behaviors/lifestyle factors), and 4) lower urinary tract dysfunction was 31%, 31%, 19%, and 41%, respectively. Among included participants, 73% were found to have at least 1 Sleep C.A.L.M. factor, and 33% had multiple Sleep C.A.L.M. FACTORS: Results were similar upon stratification by age and nocturnal polyuria status. CONCLUSIONS: The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community-based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation.

OphthoPods: An Analysis of the Educational Content and Changes of Ophthalmology Podcasts.

Objective Podcasts are a novel modality for digitally disseminating ophthalmic knowledge, yet minimal information exists on their offerings. This study sought to describe the growth of ophthalmology podcasts, characterize their features, and analyze clinically pertinent content trends. Materials and Methods Apple Podcasts, Spotify, Google Podcasts, and Google Search were queried for English- language shows relating primarily to ophthalmology. Ninety-six podcasts and 3,594 episodes were analyzed. Results Of the 48 currently active shows, most cover general ophthalmology topics ( n = 25, 52.1%) and are run by multiple hosts ( n = 29, 60.4%) in both academics and private practice. The majority of podcasts released episodes monthly ( n = 21, 21.9%) or less frequently than monthly ( n = 36, 37.5%). Among all episodes, procedural topics ( n = 951 episodes, 26.4%) and clinical education ( n = 1385, 38.5%) were the most prevalent categories. Retina was the most represented subspecialty in podcast production, while oculoplastics and neuro-ophthalmology had the fewest podcasts. Episodes on disease pathophysiology ( p = 0.04) and published research ( p < 0.001) each declined over time. The proportion of episodes released from 2020 to 2022 that discussed digital technologies was 33.3% greater versus 2005 to 2019 ( p = 0.005). Personal retrospective episodes doubled, career guidance and patient perspectives tripled, and wellness and social justice topics increased fivefold (all p < 0.001). Conclusion In summary, the coronavirus disease 2019 pandemic coincided with a rise in ophthalmology podcasts and shifts in content. Podcasts have trended toward practical advice and technologies, reflecting their value in sharing modern, peer-to-peer pearls. Emphases on storytelling and social justice offer unique, clinically relevant perspectives compared with traditional modalities.

Drivers of calcium oxalate stone formation in the octogenarian population.

INTRODUCTION: American Urological Association (AUA) guidelines suggest metabolic testing via 24-h urine studies in high-risk, interested first-time stone formers, and recurrent stone formers. If metabolic testing is not available or otherwise not feasible, clinicians may need to utilize empiric therapy. Debility and social barriers, particularly in the elderly population, may limit the practicality of metabolic testing, and therefore, empiric therapy is of particular importance. The aim of this study is to identify whether unique urinary metabolic abnormality profiles exist for octogenarians with calcium oxalate kidney stones, as this may guide empiric stone prevention therapy more precisely in this population. MATERIALS AND METHODS: Patients with calcium oxalate stones from a single academic kidney stone center in New York, NY, were retrospectively identified in our prospectively managed database. Patient data, including demographic, clinical information, and baseline 24-h urine studies, were collected before initiating any treatment. Subjects were stratified by age (≤ 40, 41-59, 60-79, and ≥ 80 years) to compare the metabolic urinary abnormality profiles between octogenarians and other age groups. Subgroup analyses were also performed to compare results by gender and by the presence of underlying kidney dysfunction. Comparative statistical analysis was carried out using Chi-square tests, Mann-Whitney U tests, and t-tests where appropriate. RESULTS: Hypocitraturia, low urine pH, and low urine volume were most common in older patients, particularly in octogenarians. Hypercalciuria, hypernatriuria, and hyperuricosuria were more apparent in younger groups. CONCLUSION: With increasing age, hypocitraturia, low urine pH, and low urine volume were more prevalent on 24-h urine metabolic testing. We hypothesize increased comorbidity, including medical renal disease, polypharmacy, and dehydration are possible factors contributing to this unique profile. We suggest that empiric therapy targeted towards this profile is important in very elderly stone formers in whom 24-h urine testing may not be possible. Increased hydration, increased fruit and vegetable intake, and low-dose alkali therapy are easy measures to accomplish this.

Polyuria in patients with lower urinary tract symptoms: Prevalence and etiology.

INTRODUCTION: Patients with lower urinary tract symptoms (LUTS) can be subcategorized into polyuria, normal or oliguria groups. Polyuria may be caused by pathologies including diabetes mellitus (DM), chronic kidney disease (CKD), diabetes insipidus (DI), or primary polydipsia (PPD). While fluid restriction is appropriate for some, doing so in all may result in serious complications. This study investigates the prevalence of these pathologies in LUTS patients with polyuria. MATERIALS AND METHODS: Two databases were retrospectively queried for men and women who filled out a lower urinary tract symptom score (LUTSS) questionnaire, 24-h bladder diary (24HBD) and were polyuric (>2.5 L/day). Patients were divided into four groups: poorly controlled DM, DI, an CKD grade 3 and PPD. One-way analysis of variance compared 24HBD and LUTSS questionnaires. Pearson correlation examined LUTSS and bother with 24-h voided volume (24 HVV), maximum voided volume (MVV) and total voids. RESULTS: Among 814 patients who completed a 24HBD, 176 had polyuria (22%). Of the patients with complete data, 7.8% had poorly-controlled DM, 3.1% had DI, 4.7% had CKD grade 3% and 84.4% had PPD. Amongst the four different sub-groups, significant differences were seen in 24 HVV (p < 0.001), nocturnal urine volume (NUV) (p < 0.001), MVV (p = 0.003), daytime voids (p = 0.05), nocturnal polyuria index (NPi) (p < 0.001) and nocturia index (Ni) (p = 0.002). Significance was also seen between LUTSS and bother subscore (r = 0.68, p < 0.001), LUTSS and total voids (r = 0.29, p = 0.001) and bother sub-score and total voids (r = 0.21, p = 0.019). CONCLUSIONS: 22% of patients with LUTS were found to have polyuria based on a 24HBD. Within this cohort, four sub-populations were identified as being demonstrating statistically significant differences in 24 HVV, NUV, MVV, daytime voids, NPi and Ni. Identifying the underlying etiology of polyuria should be carried out to safely treat patients with LUTS.

Outcomes of Sutureless Ahmed Glaucoma Valve Surgery: A Retrospective Study.

INTRODUCTION: This study compared the safety and efficacy of sutureless Ahmed glaucoma valve surgery (AGV standalone) to sutureless AGV plus cataract surgery (AGV-CEIOL) in Black or Hispanic patients. METHODS: Records from Black or non-white Hispanic patients who received either AGV standalone or AGV-CEIOL from 2014 to 2019 at a Bronx, New York practice were reviewed. All surgeries were performed using a sutureless technique with Tisseel fibrin glue. Primary outcomes included failure (defined as intraocular pressure (IOP) > 21 mmHg, ≤ 5 mmHg, or reduced by < 20% after the first 3 months; loss of light perception; or reoperation for glaucoma), hypertensive phase, IOP changes, and medication changes. Secondary outcomes included postoperative complications and interventions. RESULTS: A total of 203 eyes that received AGV standalone (n = 78) or AGV-CEIOL (n = 125) were analyzed. Mean follow-up duration was 42.2 ± 17.5 months, with similar cohort-specific intervals (P = 0.68). Failure among AGV-CEIOLs (44.8%, n = 56) and AGV standalones (47.4%, n = 37) occurred at similar frequencies; log-rank testing indicated comparable 5-year survival (P = 0.56). Mean IOP among AGV-CEIOLs (15.8 ± 12.1 mmHg) was greater than standalones (8.6 ± 5.1 mmHg) at post-op day 1 (P < 0.001). The AGV-CEIOL group had a 60% lower odds of experiencing a hypertensive phase after adjustment for baseline group differences (P = 0.01). Five-year IOP reduction was similar between groups in the multivariable model (P = 0.45). There were no significant differences in medications (P > 0.05 at all time points) or in total complications (P = 0.28). More standalones required reoperation (39.7%, n = 31) compared to AGV-CEIOLs (21.6%, n = 24; P = 0.007). CONCLUSIONS: Sutureless AGV-CEIOL was noninferior to sutureless AGV standalone when performed in Black or non-white Hispanic patients. The combined group experienced the hypertensive phase less frequently despite higher day 1 IOP.

A Comprehensive Urine Proteome Database Generated From Patients With Various Renal Conditions and Prostate Cancer.

Urine proteins can serve as viable biomarkers for diagnosing and monitoring various diseases. A comprehensive urine proteome database, generated from a variety of urine samples with different disease conditions, can serve as a reference resource for facilitating discovery of potential urine protein biomarkers. Herein, we present a urine proteome database generated from multiple datasets using 2D LC-MS/MS proteome profiling of urine samples from healthy individuals (HI), renal transplant patients with acute rejection (AR) and stable graft (STA), patients with non-specific proteinuria (NS), and patients with prostate cancer (PC). A total of ~28,000 unique peptides spanning ~2,200 unique proteins were identified with a false discovery rate of <0.5% at the protein level. Over one third of the annotated proteins were plasma membrane proteins and another one third were extracellular proteins according to gene ontology analysis. Ingenuity Pathway Analysis of these proteins revealed 349 potential biomarkers in the literature-curated database. Forty-three percentage of all known cluster of differentiation (CD) proteins were identified in the various human urine samples. Interestingly, following comparisons with five recently published urine proteome profiling studies, which applied similar approaches, there are still ~400 proteins which are unique to this current study. These may represent potential disease-associated proteins. Among them, several proteins such as serpin B3, renin receptor, and periostin have been reported as pathological markers for renal failure and prostate cancer, respectively. Taken together, our data should provide valuable information for future discovery and validation studies of urine protein biomarkers for various diseases.

Silicon on ultra-low-loss waveguide photonic integration platform.

We demonstrate a novel integrated silicon and ultra-low-loss Si3N4 waveguide platform. Coupling between layers is achieved with (0.4 ± 0.2) dB of loss per transition and a 20 nm 3-dB bandwidth for one tapered coupler design and with (0.8 ± 0.2) dB of loss per transition and a 100 nm 3-dB bandwidth for another. The minimum propagation loss measured in the ultra-low-loss waveguides is 1.2 dB/m in the 1590 nm wavelength regime.

Design of phase-shifted hybrid silicon distributed feedback lasers.

We present data on the design and performance analysis of phase shifted distributed feedback (DFB) lasers on the hybrid silicon platform. The lasing wavelength for various input currents and temperatures, for devices with standard quarter-wavelength, 60 µm and 120 µm-long phase shift are compared for mode stability and output power. The pros and cons of including a large phase shift region in the grating design are analyzed.

Electrically-pumped compact hybrid silicon microring lasers for optical interconnects.

We demonstrate an electrically-pumped hybrid silicon microring laser fabricated by a self-aligned process. The compact structure (D = 50 microm) and small electrical and optical losses result in lasing threshold as low as 5.4 mA and up to 65 degrees C operation temperature in continuous-wave (cw) mode. The spectrum is single mode with large extinction ratio and small linewidth observed. Application as on-chip optical interconnects is discussed from a system perspective.

A racetrack mode-locked silicon evanescent laser.

By utilizing a racetrack resonator topography, an on-chip mode locked silicon evanescent laser (ML-SEL) is realized that is independent of facet polishing. This enables integration with other devices on silicon and precise control of the ML-SEL's repetition rate through lithographic definition of the cavity length. Both passive and hybrid mode-locking have been achieved with transform limited, 7 ps pulses emitted at a repetition rate of 30 GHz. Jitter and locking range are measured under hybrid mode locking with a minimum absolute jitter and maximum locking range of 364 fs, and 50 MHz, respectively.

A distributed feedback silicon evanescent laser.

We report an electrically pumped distributed feedback silicon evanescent laser. The laser operates continuous wave with a single mode output at 1600 nm. The laser threshold is 25 mA with a maximum output power of 5.4 mW at 10 degrees C. The maximum operating temperature and minimum line width of the laser are 50 degrees C, and 3.6 MHz, respectively.

Integrated AlGaInAs-silicon evanescent race track laser and photodetector.

Here we report a racetrack resonator laser integrated with two photo-detectors on the hybrid AlGaInAs-silicon evanescent device platform. Unlike previous demonstrations of hybrid AlGaInAs-silicon evanescent lasers, we demonstrate an on-chip racetrack resonator laser that does not rely on facet polishing and dicing in order to define the laser cavity. The laser runs continuous-wave (c.w.) at 1590 nm with a threshold of 175 mA, has a maximum total output power of 29 mW and a maximum operating temperature of 60 C. The output of this laser light is directly coupled into a pair of on chip hybrid AlGaInAs-silicon evanescent photodetectors used to measure the laser output.

A hybrid AlGaInAs-silicon evanescent waveguide photodetector.

We report a waveguide photodetector utilizing a hybrid waveguide structure consisting of AlGaInAs quantum wells bonded to a silicon waveguide. The light in the hybrid waveguide is absorbed by the AlGaInAs quantum wells under reverse bias. The photodetector has a fiber coupled responsivity of 0.31 A/W with an internal quantum efficiency of 90 % over the 1.5 mum wavelength range. This photodetector structure can be integrated with silicon evanescent lasers for power monitors or integrated with silicon evanescent amplifiers for preamplified receivers.

Mode-locked silicon evanescent lasers.

We demonstrate electrically pumped lasers on silicon that produce pulses at repetition rates up to 40 GHz. The mode locked lasers generate 4 ps pulses with low jitter and extinction ratios above 18 dB, making them suitable for data and telecommunication transmitters and for clock generation and distribution. Results of both passive and hybrid mode locking are discussed. This type of device could enable new silicon based integrated technologies, such as optical time division multiplexing (OTDM), wavelength division multiplexing (WDM), and optical code division multiple access (OCDMA).

1310nm silicon evanescent laser.

We report the first 1310 nm hybrid laser on a silicon substrate. This laser operates continuous wave (C.W.) up to 105 degrees C. The room temperature threshold current of this laser is 30 mA, and the maximum single sided fiber-coupled output power is 5.5 mW.

A hybrid AlGaInAs-silicon evanescent preamplifier and photodetector.

We report the integration of a hybrid silicon evanescent waveguide photodetector with a hybrid silicon evanescent optical amplifier. The device operates at 1550 nm with a responsivity of 5.7 A/W and a receiver sensitivity of -17.5 dBm at 2.5 Gb/s. The transition between the passive silicon waveguide and the hybrid waveguide of the amplifier is tapered to increase coupling efficiency and to minimize reflections.

Experimental and theoretical thermal analysis of a Hybrid Silicon Evanescent Laser.

In this work we present both experimental and theoretical thermal analysis of an electrically pumped hybrid silicon evanescent laser. Measurements of an 850 mum long Fabry-Perot structure show an overall characteristic temperature of 51 oC, an above threshold characteristic temperature of 100 oC, and a thermal impedance of 41.8 oC/W. Finite element analysis of the laser structure predicts a thermal impedance of 43.5 oC/W, which is within 5% of the experimental results. Using the overall characteristic temperature, above threshold characteristic temperature, and the measured thermal impedance, the continuous wave output power vs. current from the laser is simulated and is in good agreement with experiment.