Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action.

It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high-throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One-day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 h. Concentration response modeling was performed on whole body gene expression data from each exposure, using measured chemical concentrations when available. Transcriptomic points of departure in larval fathead minnow were lower than apical effect concentrations across fish species but not always lower than toxic effect concentrations in other aquatic taxa like crustaceans and insects. The point of departure was highly dependent on measured chemical concentration which were often lower than the nominal concentration. Differentially expressed genes between chemicals within modes of action were compared and often showed statistically significant overlap. In addition, reproducibility between identical exposures using a positive control chemical (CuSO4) and variability associated with the transcriptomic point of departure using in silico sampling were considered. Results extend a transcriptomic-compatible fathead minnow high-throughput assay for possible use in ecological hazard screening.

Transcriptomics-Based Points of Departure for Daphnia magna Exposed to 18 Per- and Polyfluoroalkyl Substances.

Per- and polyfluoroalkyl substances (PFAS) represent a large group of contaminants of concern based on their widespread use, environmental persistence, and potential toxicity. Many traditional models for estimating toxicity, bioaccumulation, and other toxicological properties are not well suited for PFAS. Consequently, there is a need to generate hazard information for PFAS in an efficient and cost-effective manner. In the present study, Daphnia magna were exposed to multiple concentrations of 22 different PFAS for 24 h in a 96-well plate format. Following exposure, whole-body RNA was extracted and extracts, each representing five exposed individuals, were subjected to RNA sequencing. Following analytical measurements to verify PFAS exposure concentrations and quality control on processed cDNA libraries for sequencing, concentration-response modeling was applied to the data sets for 18 of the tested compounds, and the concentration at which a concerted molecular response occurred (transcriptomic point of departure; tPOD) was calculated. The tPODs, based on measured concentrations of PFAS, generally ranged from 0.03 to 0.58 µM (9.9-350 µg/L; interquartile range). In most cases, these concentrations were two orders of magnitude lower than similarly calculated tPODs for human cell lines exposed to PFAS. They were also lower than apical effect concentrations reported for seven PFAS for which some crustacean or invertebrate toxicity data were available, although there were a few exceptions. Despite being lower than most other available hazard benchmarks, D. magna tPODs were, on average, four orders of magnitude greater than the maximum aqueous concentrations of PFAS measured in Great Lakes tributaries. Overall, this high-throughput transcriptomics assay with D. magna holds promise as a component of a tiered hazard evaluation strategy employing new approach methodologies. Environ Toxicol Chem 2024;00:1-16. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Derivation of Transcriptomics-Based Points of Departure for 20 Per- or Polyfluoroalkyl Substances Using a Larval Fathead Minnow (Pimephales promelas) Reduced Transcriptome Assay.

Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that ecological hazards of most PFAS remain uncharacterized. The present study employed a high-throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response (termed a transcriptomics-based point of departure [tPOD]) in larval fathead minnows (Pimephales promelas; 5-6 days postfertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole-body expression of 1832 genes, the median tPOD for the 20 PFAS tested was 10 µM. Longer-chain carboxylic acids (12-13 C-F); an eight-C-F dialcohol, N-alkyl sulfonamide; and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations <1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole-transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sublethal effects have been reported in fish (available for 10 PFAS). Nonetheless, fathead minnow tPODs were orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes, suggesting a substantial margin of safety. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening-level potency estimates for use in ecological risk-based prioritization. Environ Toxicol Chem 2024;00:1-16. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Short-Term Transcriptomic Points of Departure Are Consistent with Chronic Points of Departure for Three Organophosphate Pesticides across Mouse and Fathead Minnow.

New approach methods (NAMs) can reduce the need for chronic animal studies. Here, we apply benchmark dose (concentration) (BMD(C))-response modeling to transcriptomic changes in the liver of mice and in fathead minnow larvae after short-term exposures (7 days and 1 day, respectively) to several dose/concentrations of three organophosphate pesticides (OPPs): fenthion, methidathion, and parathion. The mouse liver transcriptional points of departure (TPODs) for fenthion, methidathion, and parathion were 0.009, 0.093, and 0.046 mg/Kg-bw/day, while the fathead minnow larva TPODs were 0.007, 0.115, and 0.046 mg/L, respectively. The TPODs were consistent across both species and reflected the relative potencies from traditional chronic toxicity studies with fenthion identified as the most potent. Moreover, the mouse liver TPODs were more sensitive than or within a 10-fold difference from the chronic apical points of departure (APODs) for mammals, while the fathead minnow larva TPODs were within an 18-fold difference from the chronic APODs for fish species. Short-term exposure to OPPs significantly impacted acetylcholinesterase mRNA abundance (FDR p-value <0.05, |fold change| ≥2) and canonical pathways (IPA, p-value <0.05) associated with organism death and neurological/immune dysfunctions, indicating the conservation of key events related to OPP toxicity. Together, these results build confidence in using short-term, molecular-based assays for the characterization of chemical toxicity and risk, thereby reducing reliance on chronic animal studies.

Feeding in mixoplankton enhances phototrophy increasing bloom-induced pH changes with ocean acidification.

Plankton phototrophy consumes CO2, increasing seawater pH, while heterotrophy does the converse. Elevation of pH (>8.5) during coastal blooms becomes increasingly deleterious for plankton. Mixoplankton, which can be important bloom-formers, engage in both photoautotrophy and phagoheterotrophy; in theory, this activity could create a relatively stable pH environment for plankton growth. Using a systems biology modelling approach, we explored whether different mixoplankton functional groups could modulate the environmental pH compared to the extreme activities of phototrophic phytoplankton and heterotrophic zooplankton. Activities by most mixoplankton groups do not stabilize seawater pH. Through access to additional nutrient streams from internal recycling with phagotrophy, mixoplankton phototrophy is enhanced, elevating pH; this is especially so for constitutive and plastidic specialist non-constitutive mixoplankton. Mixoplankton blooms can exceed the size of phytoplankton blooms; the synergisms of mixoplankton physiology, accessing nutrition via phagotrophy as well as from inorganic sources, enhance or augment primary production rather than depressing it. Ocean acidification will thus enable larger coastal mixoplankton blooms to form before basification becomes detrimental. The dynamics of such bloom developments will depend on whether the mixoplankton are consuming heterotrophs and/or phototrophs and how the plankton community succession evolves.

Mucus-Trap-Assisted Feeding Is a Common Strategy of the Small Mixoplanktonic Prorocentrum pervagatum and P. cordatum (Prorocentrales, Dinophyceae).

Prorocentrum comprises a diverse group of bloom-forming dinophytes with a worldwide distribution. Although photosynthetic, mixoplanktonic phagotrophy has also been described. Recently, the small P. cf. balticum was shown to use a remarkable feeding strategy by crafting globular mucus traps to capture and immobilize potential prey. Here we present evidence showing that two additional related species, the recently described P. pervagatum and the cosmopolitan bloom-forming P. cordatum, also produce large (80-120 µm) mucus traps supporting their mixoplanktonic activity. Prey are captured within the traps either through passive entanglement upon contact with the outside surface, or through active water movement created by rotating Prorocentrum cells eddying particles to the inside surface where trapped live prey cells became immobilized. Entrapment in mucus assisted deployment into the prey of a peduncle extruded from the apical area of the Prorocentrum cell. Phagotrophy by P. pervagatum supported faster growth compared to unfed controls and time series quantification of food vacuoles revealed ingestion rates of ca. 10-12 Teleaulax prey cells day-1. Model calculations show clear advantages of deploying a mucus trap for increasing prey encounter rates. This study demonstrates that the large size and immobilization properties of mucus traps successfully increase the availability of prey for small Prorocentrum species, whose peduncle feeding mode impedes consumption of actively moving prey, and that this strategy is common among certain clades of small planktonic Prorocentrum species.

Clinical Validation of an Adult-acquired Buried Penis Classification System Based on Standardized Evaluation of the Penis, Abdomen, and Scrotum.

OBJECTIVE: To clinically validate a previously developed adult-acquired buried penis (AABP) classification system that is based on a standardized preoperative physical examination that subtypes patients by their penile skin/escutcheon complex (P), abdominal pannus (A), and scrotal skin (S). METHODS: The Trauma and Urologic Reconstruction Network of Surgeons (TURNS) database was used to create an AABP cohort. Patients were retrospectively classified using the previously described PAS classification system. The frequency of subtypes, surgical methods utilized for AABP repair, and correlations between PAS classification and surgery subtypes were analyzed. RESULTS: The final cohort consisted of 101 patients from 10 institutions. Interrater reliability between two reviewers was excellent (κ = 0.95). The most common subtypes were P2c (contributory escutcheon+insufficient penile skin; 27%) and P2a (contributory escutcheon+sufficient penile skin; 21%) for penile subtypes, A0 (no pannus; 41%) and A1 (noncontributory pannus; 39%) for abdominal subtypes, and S0 (normal scrotal skin with preserved scrotal sulcus; 71%) for scrotal subtypes. AABP repair procedures included escutcheonectomy (n = 59, 55%), scrotoplasty (n = 51, 48%), split-thickness skin grafting (n = 50, 47%), penile skin excision (n = 47, 44%) and panniculectomy (n = 7, 7%). P, A, and S subtypes were strongly associated with specific AABP surgical techniques. CONCLUSION: The PAS classification schema adequately describes AABP heterogeneity, is reproducible among observers, and correlates well with AABP surgery types. Future work will focus on how PAS subtypes affect both surgical and patient-centered outcomes.

Low rates of bacterivory enhances phototrophy and competitive advantage for mixoplankton growing in oligotrophic waters.

With climate change, oceans are becoming increasingly nutrient limited, favouring growth of prokaryotic picoplankton at the expense of the larger protist plankton whose growth support higher trophic levels. Constitutive mixoplankton (CM), microalgal plankton with innate phototrophic capability coupled with phagotrophy, graze on these picoplankton, indirectly exploiting the excellent resource acquisition abilities of the prokaryotes. However, feeding rates can be very low (e.g., a few bacteria d-1). For the first time, the significance of such low consumption rates has been quantified. We find that while prokaryote-carbon (C) supply to CM grown at non-limiting light was so low that it may appear insignificant (< 10%), contributions of nitrogen (N) and phosphorus (P) from ingestions of 1-12 prokaryotes d-1 were significant. Under limiting light, contributions of ingested C increased, also raising the contributions of N and P. The order of nutritional importance for CM growth from predation was P > N > C. Further, provision of N through internal recycling of ingested prey-N stimulates C-fixation through photosynthesis. Importantly, coupled photo-phago-mixoplanktonic activity improved CM resource affinities for both inorganic and prey-bound nutrients, enhancing the nutritional status and competitiveness of mixoplankton. With warming oceans, with increased prokaryote abundance, we expect CM to exhibit more phagotrophy.

The Mixoplankton Database (MDB): Diversity of photo-phago-trophic plankton in form, function, and distribution across the global ocean.

Protist plankton are major members of open-water marine food webs. Traditionally divided between phototrophic phytoplankton and phagotrophic zooplankton, recent research shows many actually combine phototrophy and phagotrophy in the one cell; these protists are the "mixoplankton." Under the mixoplankton paradigm, "phytoplankton" are incapable of phagotrophy (diatoms being exemplars), while "zooplankton" are incapable of phototrophy. This revision restructures marine food webs, from regional to global levels. Here, we present the first comprehensive database of marine mixoplankton, bringing together extant knowledge of the identity, allometry, physiology, and trophic interactivity of these organisms. This mixoplankton database (MDB) will aid researchers that confront difficulties in characterizing life traits of protist plankton, and it will benefit modelers needing to better appreciate ecology of these organisms with their complex functional and allometric predator-prey interactions. The MDB also identifies knowledge gaps, including the need to better understand, for different mixoplankton functional types, sources of nutrition (use of nitrate, prey types, and nutritional states), and to obtain vital rates (e.g. growth, photosynthesis, ingestion, factors affecting photo' vs. phago' -trophy). It is now possible to revisit and re-classify protistan "phytoplankton" and "zooplankton" in extant databases of plankton life forms so as to clarify their roles in marine ecosystems.

Thermal Infrared Camera Imaging to Aid Necrotizing Soft Tissue Infections of the Genitalia Management.

OBJECTIVE: To determine if imaging with a thermal infrared camera might aid clinicians with diagnosis of equivocal necrotizing soft tissue infections of the genitalia (NSTIG) cases and help surgeons when determining appropriate surgical resection margins. MATERIALS/METHODS: For 12 months at a single tertiary academic hospital, sequential patients already undergoing exploration for acute scrotum had preoperative photography with an infrared camera (FLIR C5). We compared infrared and standard preoperative photography with operative reports and postoperative photography to investigate if infrared photography corresponded with operative findings in severe scrotal infections-specifically the viability of the skin and the ultimate surgical resection margins. RESULTS: A total of 16 patients were included. The pre-operative infrared photos directly correlated with resection margins in 13 of 16 (81%) patients. Notably, areas with a relatively lower (cooler) infrared intensity corresponded well to both visibly necrotic tissue when discrete and areas with large underlying fluid collections. Diffuse warm signal relative to surrounding skin correlated with cellulitis and viable skin. CONCLUSION: In this observational study, infrared photography corresponded well with physical exam and operative findings. There may be a role for augmented temperature photography in the diagnosis and triage of scrotal infections. More research with standardized temperature gating of infrared signal and controls with normal or nonacute scrotums are needed to elucidate the clinical utility for infrared photograph.

Pilot testing and optimization of a larval fathead minnow high throughput transcriptomics assay.

Concentrations at which global gene expression profiles in cells or animals exposed to a test substance start to differ significantly from those of controls have been proposed as an alternative point of departure for use in screening level hazard assessment. The present study describes pilot testing of a high throughput compatible transcriptomics assay with larval fathead minnows. One day post hatch fathead minnows were exposed to eleven different concentrations of three metals, three selective serotonin reuptake inhibitors, and four neonicotinoid-like compounds for 24 h and concentration response modeling was applied to whole body gene expression data. Transcriptomics-based points of departure (tPODs) were consistently lower than effect concentrations reported in apical endpoint studies in fish. However, larval fathead minnow-based tPODs were not always lower than concentrations reported to elicit apical toxicity in other aquatic organisms like crustaceans or insects. Random in silico subsampling of data from the pilot assays was used to evaluate various assay design and acceptance considerations such as transcriptome coverage, number of replicate individuals to sequence per treatment, and minimum number of differentially expressed genes to produce a reliable tPOD estimate. Results showed a strong association between the total number of genes for which a concentration response relationship could be derived and the overall variability in the resulting tPOD estimates. We conclude that, for our current assay design and analysis pipeline, tPODs based on fewer than 15 differentially expressed genes are likely to be unreliable for screening and that interindividual variability in gene expression profiles appears to be a more significant driver of tPOD variability than sample size alone. Results represent initial steps toward developing high throughput transcriptomics assays for use in ecological hazard screening.

Adult-Acquired Buried Penis Classification and Surgical Management.

In this article, the authors discuss the epidemiology, pathophysiology, and initial work-up for men with adult-acquired buried penis syndrome (AABP). Given the significant heterogeneity of AABP, a classification system is proposed which classifies the condition by the status of the abdominal pannus, the escutcheon, the penile skin and the scrotal skin, and their respective fascial attachments. Classification is achieved by a uniform assessment of anatomy using the proposed standardized preoperative photos. Various surgical strategies to repair AABP are proposed which, importantly, should be in line with the patient-centered goals and also differ widely with the condition.

Management of Necrotizing Soft Tissue Infections (Fournier's Gangrene) and Surgical Reconstruction of Debridement Wound Defects.

In this article, the authors discuss the epidemiology, pathophysiology, and mechanism of spread of necrotizing soft-tissue infections of the genitalia, including classification schemas. The authors then discuss the acute clinical management of the disease, including suggestions for ways to improve surgical debridements (such that eventual reconstructions are simpler), ways to predict disease severity using laboratory, vital sign, and physical examination findings, and suggestions for initial antimicrobial treatments. Finally, reconstructive techniques and algorithms to ensure that the reconstructive goals of coverage, function, and cosmesis are met, are discussed, including the management of postoperative complications.

Favorable Outcomes With Early Component Separation, Primary Closure of Necrotizing Soft Tissue Infections of the Genitalia (Fournier's Gangrene) Debridement Wound Defects.

OBJECTIVE: To evaluate the efficacy of early necrotizing soft-tissue infections of the genitalia (NSTIG) component separation, primary wound closure (CSC). We hypothesized that early CSC would be safe, decrease the need for split-thickness skin grafting (STSG) and decrease wound convalescence time. MATERIALS/METHODS: Management of consecutive NSTIG patients from a single institution were evaluated. Three cohorts emerged: 1) those managed/closed by a reconstructive urologist (URO) using CSC principles (wide genital tissue mobilization with primary closure, when possible, +/- STSG), 2) those managed/closed by the general surgery/burn service, and 3) those managed conservatively with secondary closure. Total NSTIG anatomic extent (AE) was determined by assessing involvement of the penis, scrotum, perineum and suprapubic region, and ranged from 1 (<50% involvement of one area) to 8 (>50% involvement in all 4 areas). RESULTS: Of 84 FG patients meeting study criteria, 48 (57%) were closed primarily and 36 were left to heal by secondary intention. AE was greatest in patients managed by general surgery/burn service (4.5 ± 1.5), followed by URO (2.7 ± 1.8) and secondary intention cases (1.3 ± 0.5). Secondary procedure rates were similar between closure/non-closure cohorts (6.3% v 11%; P = 0.67). STSG use was predicted by wound size (though not time to closure)-specifically with suprapubic and/or penile wounds of >50% involvement. Wound convalescence time decreased by 64% when wounds were closed versus left open, controlling for AE. CONCLUSION: Early, same-admission primary closure of stable NSTIG wounds is safe and decreases wound convalescence time by over 60%.

Nephrostomy Balloon and Sheath Suprapubic Tube Placement-A Minimally Invasive Approach to Large Caliber Suprapubic Tube Placement.

Suprapubic tubes (SPT) are a vital tool in the management of complex urologic voiding conditions. There are numerous methods of SPT placement, each with pros/cons: peel-away kits are easy to place, but often have small caliber SPTs, that is, 12 or 14 Fr, prone to kinking, that require serial upsizing to achieve the desired caliber; open SPT placements permit an initial large caliber SPT but are more invasive, particularly in obese patients. This video demonstrates a minimally invasive technique for SPT placement in patients with preserved urethral access to the bladder that safely allows for initial, precise placement of large caliber (>20F) catheters using the Nephromax nephrostomy balloon/sheath (NBS-SPT). Technique: A 6″ 17G Tuohy spinal needle is placed percutaneously 3 cm above the pubis (generally in the abdominal crease), 1-2 cm off midline towards the side the patient prefers to keep the drainage bag. The needle is angled to enter the bladder dome in the midline, which is visualized cystoscopically with a full bladder. The angling will allow the catheter to lie flat and decrease kinking. The stylette is removed and a stiff wire is advanced. A 2 cm horizontal skin incision is made. A 24 Fr NBS is advanced into the bladder under vision and inflated to 18 ATM. The balloon is then deflated/removed and the SPT is passed through the sheath into the bladder. Once inflated, the sheath removed and the SPT is secured to the skin. Study: A 10-year retrospective review of NBS-SPT placements at a single institution was performed, analyzing patient characteristics, surgical details, and surgical outcomes. NBS-SPT was attempted 65 times over the study period. The most common indications included acquired/congenital neurogenic bladder (48%) and urinary retention (25%). A simultaneous additional procedure (eg, cytolitholapaxy, bladder neck incision) was performed in 31% of NBS-SPTs. Median body mass index was 29.5 (interquartile range: 25-33.9) and 34% had prior abdominal procedures. Median operative time (NBS-SPT only) was 16 minutes (interquartile range: 14-20). All procedures were successful in placing a catheter 20F. Thirty-day Clavien I/II complication rate was 18% (hematuria n = 3; cellulitis n = 4; early SPT exchange for clogging n = 5); A Clavien IIIb complication occurred in one patient with hematuria requiring fulguration. First SPT exchange in clinic was successful in 95%, with 2 patients requiring replacement under anesthesia. NBS-SPT is a safe and efficient minimally invasive technique for initial, precise placement of large caliber SPT in patients with urethral bladder access.

Deuterium in marine organic biomarkers: toward a new tool for quantifying aquatic mixotrophy.

The traditional separation between primary producers (autotrophs) and consumers (heterotrophs) at the base of the marine food web is being increasingly replaced by the paradigm that mixoplankton, planktonic protists with the nutritional ability to use both phago(hetero)trophy and photo(auto)trophy to access energy are widespread globally. Thus, many 'phytoplankton' eat, while 50% of 'protozooplankton' also perform photosynthesis. Mixotrophy may enhance primary production, biomass transfer to higher trophic levels and the efficiency of the biological pump to sequester atmospheric CO2 into the deep ocean. Although this view is gaining traction, science lacks a tool to quantify the relative contributions of autotrophy and heterotrophy in planktonic protists. This hinders our understanding of their impacts on carbon cycling within marine pelagic ecosystems. It has been shown that the hydrogen (H) isotopic signature of lipids is uniquely sensitive to heterotrophy relative to autotrophy in plants and bacteria. Here, we explored whether it is also sensitive to the trophic status in protists. The new understanding of H isotope signature of lipid biomarkers suggests it offers great potential as a novel tool for quantifying the prevalence of mixotrophy in diverse marine microorganisms and thus for investigating the implications of the 'mixoplankton' paradigm.

'Boom-and-busted' dynamics of phytoplankton-virus interactions explain the paradox of the plankton.

Rapid virus proliferation can exert a powerful control on phytoplankton host populations, playing a significant role in marine biogeochemistry and ecology. We explore how marine lytic viruses impact phytoplankton succession, affecting host and nonhost populations. Using an in silico food web we conducted simulation experiments under a range of different abiotic and biotic conditions, exploring virus-host-grazer interactions and manipulating competition, allometry, motility and cyst cycles. Virus-host and predator-prey interactions, and interactions with competitors, generate bloom dynamics with a pronounced 'boom-and-busted' dynamic (BBeD) which leads to the suppression of otherwise potentially successful phytoplankton species. The BBeD is less pronounced at low nutrient loading through distancing of phytoplankton hosts, while high sediment loading and high nonhost biomass decrease the abundance of viruses through adsorption. Larger hosts are inherently more distanced, but motility increases virus attack, while cyst cycles promote spatial and temporal distancing. Virus control of phytoplankton bloom development appears more important than virus-induced termination of those blooms. This affects plankton succession - not only the growth of species infected by the virus, but also those that compete for the same resources and are collectively subjected to common grazer control. The role of viruses in structuring plankton communities via BBeDs can thus provide an explanation for the paradox of the plankton.

Prospective Comparison of Opioid vs Nonopioid Pain Regimen After Ureteroscopy.

Objective: We wanted to evaluate two new treatment phases within our practice, including a nonopioid pathway, to determine the effect on opioid usage, health care utilization, and pain following ureteroscopy. Methods: Patients undergoing ureteroscopic lithotripsy were enrolled in a study utilizing text messaging to evaluate postoperative pain and opioid usage. Our historical postoperative pain regimen included #30 oxycodone. Patients in the N15 cohort were given improved counseling, preanesthesia acetaminophen, and #15 oxycodone. With further experience, narcotics were removed entirely from our postoperative care plan (N0) and replaced with a nonopioid multimodal regimen. Results: There were 61 and 58 patients in cohorts N15 and N0, respectively, with no difference in demographics, stone, or procedure details between each cohort. No difference in pain scores was detected between the N15 and N0 cohorts (p = 0.14). The median time to pain resolution was postoperative day (POD) 4 for cohort N15 and POD 3 for cohort N0 (p = 0.06). In the N0 cohort, nine patients required postoperative narcotics (15.5%; average of 2.4 pills/patient). There was no significant difference in emergency department visits, phone calls, or clinic visits (p = 0.17) between each cohort. Conclusions: Patients undergoing ureteroscopy have adequate postoperative pain control with a nonopioid treatment regimen, although some patients will still ultimately require narcotics.