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Objective: To report outcomes, complications, and risk factors of a population cohort undergoing male-to-female gender affirmation surgery via penile-inversion vaginoplasty by a single surgeon at a large academic institution. As gender dysphoria awareness increases among the medical community, so does the population of patients seeking gender-affirmation surgery.Materials and Methods: A prospectively maintained database of patients undergoing penile-inversion vaginoplasty was retrospectively queried for all available patients with at least 1 week of postoperative follow-up. Univariate and multivariate analyses were performed using Fisher's exact test and logistic regression, respectively, in order to evaluate relationship of risk factors to complications at 30, 60, and 90 days, as well as the likelihood of revision/reoperation.Results: From November 2016 to April 2018, 240 penile-inversion vaginoplasties were performed. Median follow-up was 87 days. When accounting for competing risk factors, only noncompliance with postoperative dilation regimen and activity restriction was significantly associated with increased risk of complications or reoperation/revision. Overall incidence of reoperation/revision was 7.9% (n = 19). Reasons for reoperation included cosmesis (3.8%; n = 9), neovaginal stenosis (2.1%; n = 5), and wound dehiscence (0.8%; n = 2), with less than 0.5% (n = 1) reoperations for meatal stenosis, hematoma or rectovaginal fistula, respectively. Incidence of Clavien IIIa-b complications was 1.7% (n = 4). There were no Clavien IV-V complications.Conclusion: At short-term follow-up, gender-affirmation surgery is associated with low rates of reoperation and revision and few major complications when performed by an experienced, high-volume surgeon. Patient selection and compliance is imperative. Increased reporting among surgeons is necessary to continue to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Comparative effectiveness research (CER) is imperative for objective and balanced assessment of treatment outcomes. CER that uses administrative databases (AD-CER) affords unique opportunities for large scale data analyses that potentially transcend limitations of small institutional datasets. Prostate cancer has received much attention from the AD-CER research community, whereas non-prostate genitourinary malignancies are less well-studied. The objective of this article is to review the currently available AD-CER that has been published in the non-prostate genitourinary malignancies space. [ABSTRACT FROM AUTHOR]

This paper provides an example of how one group of fishermen, operating in an ITQ fishery in British Columbia, Canada, used a licence bank to attempt to mitigate the negative consequences of ITQs. After ten years in operation, the licence bank is self-sustaining and has realized modest and limited success. The authors identify a number of lessons learned from the experience, as well as highlight the opportunities that licence banks offer as an alternative mechanism to redress the negative consequences of ITQs. [ABSTRACT FROM AUTHOR]

The human pathogen Shigella flexneri subverts host function and defenses by deploying a cohort of effector proteins via a type III secretion system. The IpaH family of 10 such effectors mimics ubiquitin ligases but bears no sequence or structural homology to their eukaryotic counterpoints. Using rates of 125I-polyubiquitin chain formation as a functional read out, IpaH9.8 displays V-type positive cooperativity with respect to varying concentrations of its Ubc5B~125I-ubiquitin thioester co-substrate in the nanomolar range ([S]1/2 = 140 ± 32 nM; n = 1.8 ± 0.1) and cooperative substrate inhibition at micromolar concentrations ([S]1/2 = 740 ± 240 nM; n = 1.7 ± 0.2), requiring ordered binding to two functionally distinct sites per subunit. The isosteric substrate analog Ubc5BC85S-ubiquitin oxyester acts as a competitive inhibitor of wild-type Ubc5B~125I-ubiquitin thioester (Ki = 117 ± 29 nM), whereas a Ubc5BC85A product analog shows noncompetitive inhibition (Ki = 2.2 ± 0.5 µM), consistent with the two-site model. Re-evaluation of a related IpaH3 crystal structure (PDB entry 3CVR) identifies a symmetric dimer consistent with the observed cooperativity. Genetic disruption of the predicted IpaH9.8 dimer interface reduces the solution molecular weight and significantly ablates the kcat but not [S]1/2 for polyubiquitin chain formation. Other studies demonstrate that cooperativity requires the N-terminal leucine-rich repeat-targeting domain and is transduced through Phe395. Additionally, these mechanistic features are conserved in a distantly related SspH2 Salmonella enterica ligase. Kinetic parallels between IpaH9.8 and the recently revised mechanism for E6AP/UBE3A (Ronchi, V. P., Klein, J. M., and Haas, A. L. (2013) E6AP/UBE3A ubiquitin ligase harbors two E2~ubiquitin binding sites. J. Biol. Chem. 288, 10349-10360) suggest convergent evolution of the catalytic mechanisms for prokaryotic and eukaryotic ligases. [ABSTRACT FROM AUTHOR]

A 69-year-old homeless African American male with prostate cancer diagnosed 2 years prior presents a large mass in the right thigh. An evaluation of the patient revealed a prostate-specific antigen of 9362 ng/mL. Biopsy of the leg mass was performed and final pathology indicated metastatic adenocarcinoma of the prostate. Although metastatic prostate cancer presents most commonly in bone, lymph nodes, lungs, and liver, metastatic disease presenting as a soft tissue mass is extremely rare (Bubendorf et al, 2000; Molenaar et al, 1996; Ward and Bourken, 1984). The advent of screening with prostate-specific antigen has led to earlier diagnosis of lower-grade disease, yet underserved populations continue to present with aggressive and morbid disease (Winer et al, 2014). [ABSTRACT FROM AUTHOR]

A 71-year-old female presented with a large, protuberant abdominal mass, and was found to have both a left renal mass and a biopsy-proven neuroendocrine tumor of the ileocecal valve. Ultimately, right hemicolectomy revealed a well-differentiated and low-grade neuroendocrine tumor of the ileocecal valve, whereas left radical nephrectomy revealed a 23 cm × 22 cm × 15 cm renal cell carcinoma, chromophobe-type (RCC-CT) weighing 3564 g. RCC-CT represents a small portion of diagnosed RCC, and generally portends a more favorable prognosis than other variants. Modern reports of renal tumors exceeding 20 cm are exceedingly rare. In spite of massive size, favorable histology may allow for surgical cure. [ABSTRACT FROM AUTHOR]

Employing125 I-polyubiquitin chain formation as a functional readout of ligase activity, biochemical and biophysical evidence demonstrates that catalytically active E6-associated protein (E6AP)/UBE3A is an oligomer. Based on an extant structure previously discounted as an artifact of crystal packing forces, we propose that the fully active formof E6AP is a trimer, analysis of which reveals a buried surface of 7508 Ų and radially symmetric interacting residues that are conserved within the Hect (homologous to E6AP C terminus) ligase superfamily. An absolutely conserved interaction between Phe272 and a hydrophobic pocket present on the adjacent subunit is critical for trimer stabilization because mutation disrupts the oligomer and decreases kcat 62-fold but fails to affect E2~ubiquitin binding or subsequent formation of the Hect domain Cys820ubiquitin thioester catalytic intermediate. Exogenous N-acetylphenylalanylamide reversibly antagonizes Phe727 -dependent trimer formation and catalytic activity (Ki=12 mM), as does a conserved α-helical peptide corresponding to residues 474-490 of E6AP isoform1 (KiµM) reported to bind the hydrophobic pocket of other Hect ligases, presumably blocking Phe727 intercalation and trimer formation. Conversely, oncogenic human papillomavirus-16/18 E6 protein significantly enhances E6AP catalytic activity by promoting trimer formation (Kactivation 1.5 nM) through the ability of E6 to form homodimers. Recombinant E6 protein additionally rescues the kcat defect of the Phe727 mutation and that of a specific loss-of-function Angelman syndrome mutation that promotes trimer destabilization. The present findings codify otherwise disparate observations regarding the mechanism of E6AP and related Hect ligases in addition to suggesting therapeutic approaches for modulating ligase activity. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of surgeon-administered Transversus Abdominis Plane block (sTAP) on opioid usage and length of stay (LOS).Methods: Starting in April 2018, two surgeons at our institution gradually introduced sTAP for radical cystectomy (RC) patients. We performed a retrospective observational cohort analysis of RC patients catalogued in a prospectively maintained database using the Enhanced Recovery After Surgery Interactive Auditing System. Two surgeons adopted the sTAP block technique in April 2018. We included patients undergoing RC for bladder malignancy under Enhanced Recovery After Surgery protocol between January 2017 and August 2020. Primary outcomes included LOS, and postoperative day (POD) 0-3 total opioids consumption measured by morphine milligram equivalents (MME). Multivariable linear or logistic models evaluated the association of TAP with outcomes while controlling for potential confounders.Results: Among 178 patients included in analysis, 84 patients underwent sTAP block and 94 did not. Multivariable analysis demonstrated significantly lower POD 0-3 total opioid usage (106.4 vs 192.2 MME, P = .004), and mean LOS (5.6 vs 7.7 days, P <.001) among the sTAP group.Conclusion: sTAP appears to be an effective adjunct to RC care associated with improved LOS, and POD 0-3 opioid consumption. Further studies are needed to optimize TAP block technique and anesthetic composition. [ABSTRACT FROM AUTHOR]

Background: Nephroureterectomy (NU) remains the gold-standard for upper-tract urothelial carcinoma (UTUC). However, nephron-sparing management (NSM), specifically segmental ureterectomy (SU) for urothelial tumors distal to the renal pelvis may offer decreased risk of renal insufficiency and equivalent cancer control.Objectives: To identify patient-specific and facility-related factors that are associated with the selection of SU vs. NU for patients with clinically localized, high-grade, ureteral UTUC.Design, Setting, Participants: We searched the National Cancer Database between 2004 and 2015 for patients with high-grade, clinically localized, primary ureteral UTUC managed by either NU or SU.Outcome Measurements and Statistical Analysis: Univariate and multivariate analysis was performed to assess patient, disease-specific, facility and treatment-related factors associated with SU vs. NU. Since surgical approach was only indexed after 2010, separate multivariable logistic regressions were performed including and excluding surgical approach in order to capture patients treated between 2004 and 2009. Survival analysis utilized Kaplan-Meier methods and Cox proportional hazards regression.Results and Limitations: Multivariate analysis including surgical approach demonstrated that among other factors, higher clinical stage (P = 0.034), larger tumor size (P < 0.001), the addition of neoadjuvant chemotherapy (P = 0.002), and the utilization of minimally invasive surgery (P < 0.05) decreased the likelihood of patients receiving SU. In this same cohort, institutions with larger facility volumes (P = 0.038) and performing intraoperative lymph node dissection (P < 0.001) were associated with a higher probability of SU. Excluding surgical approach, once again more advanced clinical stage (P = 0.005), larger tumor size (P < 0.001), and neoadjuvant chemotherapy (P = 0.003) decreased the probability of patients receiving SU, while increasing age (P = 0.049) and intraoperative lymph node dissection (P < 0.001) were more closely associated with SU compared to NU. No differences were noted in pathological T stage (P > 0.05), 30-day readmission (P = 0.7), 30-day mortality (P = 0.09), and 90-day mortality (P = 0.157) on multivariate analysis between SU and NU. Additionally, no significant differences were seen in median overall survival between patients receiving SU or NU (53 vs. 50 months; P = 0.143).Conclusions: Comparable outcomes suggest segmental ureterectomy for high-grade ureteral UTUC is appropriate in well-selected patients. Practice patterns appear consistent with guideline recommendations (decreased tumor size and lower clinical stage favor SU), but treatment disparities may exist based on a multitude of patient, pathologic- and facility-related factors. Improved dissemination of knowledge regarding practice patterns and outcomes of SU for UTUC of the ureter has the potential to improve delivery of NSM in appropriate patients.Patient Summary: In this study, we examined factors associated with different surgical procedures for cancer of the ureter. We found that smaller tumor sizes, a less advanced clinical stage, intraoperative lymph dissection higher facility volumes tended to favor kidney-sparing treatment, while survival outcomes appear comparable to renal extirpation. [ABSTRACT FROM AUTHOR]

A 40-year-old male with presented to the clinic with the chief complaint of right inguinal pain radiating to his right testicle and right thigh with no history of trauma, fever, chills, dysuria, hematuria, or unprotected sexual activity. Physical exam revealed right testicular tenderness with no palpable abnormality of the bilateral testes or spermatic cords. Scrotal ultrasound was performed and was unremarkable for testicular or other intrascrotal pathology. Concurrently, chronic low back pain had prompted a lumbar CT to be performed, which was indeterminate, but subsequent lumbar MRI performed three months later revealed abnormal signals in the vertebral bodies of T12, L3, and L5, concerning for occult metastatic disease or multiple myeloma. PET-CT was performed revealing hypermetabolic lesions throughout the axial skeleton and, most notably, hypermetabolic lesions in the left inguinal and left upper scrotum. At this time, about 4 months after the original visit, physical exam revealed a palpable mobile mass in the left upper scrotum that was distinct from the left testicle, and another mass palpable near the left inguinal ring. [ABSTRACT FROM AUTHOR]

Abstract: Autonomous systems have advanced substantially, yet on-board energy capacity still constrains endurance. Liquid hydrogen (LH2) fuel storage coupled with a high efficiency fuel cell may offer greater endurance. An LH2 storage system has been developed, featuring a lightweight dewar with active pressure control. The dewar has 20.46 L internal volume, yielding ≤7.6 kWh kg−1 specific energy and ≤1.2 Wh L−1 energy density (LHV basis) depending on fuel withdrawal rate and ambient conditions. It demonstrated 48 h continuous flight in the Naval Research Laboratory's Ion Tiger unmanned air vehicle, which is ∼85% longer than prior gaseous hydrogen (GH2) fueled flights, with the same dry mass as the GH2 system. Design considerations included matching the LH2 evaporation rate and variable consumption rate, and satisfying constraints imposed by the existing aircraft. Heat transfer models were used to design for low dewar heat leak, which is necessary to balance evaporation and consumption. The heat leak depends on ambient temperature, with evaporation ranging from 16 g h−1 at 240 K to 29 g h−1 at 300 K, at 275 kPa storage pressure. The LH2/GH2/dewar system takes ≥4 h to reach thermodynamic equilibrium after fueling. LH2 can extend the endurance of small autonomous systems, but at the expense of greater design effort and reduced operational flexibility. [Copyright &y& Elsevier]

Imido ligand transfer occurs when Os(TTP)(NC6H4NO2)2 (TTP=dianion of 5,10,15,20-tetra(p-tolyl)porphyrin) is treated with excess phosphine. The rate of transfer to PMe3−xPhx (x=0, 1, 2, 3) and P(OMe)2Ph depends on the basicity and the steric properties of the phosphine. No imido ligand transfer is observed when Os(TTP)(NC6H4NO2)2 is treated with excess dimethyl fumarate, styrene, cis-cyclooctene, or 2,3-dimethylbutene under a variety of reaction conditions. [Copyright &y& Elsevier]