Gene Function is a Driver of Activin Signaling Pathway Evolution Following Whole-Genome Duplication in Rainbow Trout (Oncorhynchus mykiss).

The genomes of plant and animal species are influenced by ancestral whole-genome duplication (WGD) events, which have profound impacts on the regulation and function of gene networks. To gain insight into the consequences of WGD events, we characterized the sequence conservation and expression patterns of ohnologs in the highly duplicated activin receptor signaling pathway in rainbow trout (RBT). The RBT activin receptor signaling pathway is defined by tissue-specific expression of inhibitors and ligands and broad expression of receptors and Co-Smad signaling molecules. Signaling pathway ligands exhibited shared expression, while inhibitors and Smad signaling molecules primarily express a single dominant ohnolog. Our findings suggest that gene function influences ohnolog evolution following duplication of the activin signaling pathway in RBT.

Private equity in radiology - Why aren't we more concerned?

There has been recent scrutiny of private equity involvement in the healthcare market by federal and state governmental agencies who are concerned about the corporatization and financialization of healthcare in the United States. Data is emerging that patient costs increase, quality of healthcare decreases, physician autonomy decreases, and physician burnout and moral injury increases when corporate interests like private equity enter the medical market. Like other medical specialties, the field of radiology has been affected by corporatization and radiologists should understand how private equity interests may affect individual radiologists and the radiology workforce on a larger scale.

Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) incidence has risen steadily over the last decade. Elevated lipid uptake and storage is required for ccRCC cell viability. As stored cholesterol is the most abundant component in ccRCC intracellular lipid droplets, it may also play an important role in ccRCC cellular homeostasis. In support of this hypothesis, ccRCC cells acquire exogenous cholesterol through the high-density lipoprotein receptor SCARB1, inhibition or suppression of which induces apoptosis. Here, we showed that elevated expression of 3 beta-hydroxy steroid dehydrogenase type 7 (HSD3B7), which metabolizes cholesterol-derived oxysterols in the bile acid biosynthetic pathway, is also essential for ccRCC cell survival. Development of an HSD3B7 enzymatic assay and screening for small-molecule inhibitors uncovered the compound celastrol as a potent HSD3B7 inhibitor with low micromolar activity. Repressing HSD3B7 expression genetically or treating ccRCC cells with celastrol resulted in toxic oxysterol accumulation, impaired proliferation, and increased apoptosis in vitro and in vivo. These data demonstrate that bile acid synthesis regulates cholesterol homeostasis in ccRCC and identifies HSD3B7 as a plausible therapeutic target. SIGNIFICANCE: The bile acid biosynthetic enzyme HSD3B7 is essential for ccRCC cell survival and can be targeted to induce accumulation of cholesterol-derived oxysterols and apoptotic cell death.

Engineering transcriptional regulation for cell-based therapies.

A major aim in the field of synthetic biology is developing tools capable of responding to user-defined inputs by activating therapeutically relevant cellular functions. Gene transcription and regulation in response to external stimuli are some of the most powerful and versatile of these cellular functions being explored. Motivated by the success of chimeric antigen receptor (CAR) T-cell therapies, transmembrane receptor-based platforms have been embraced for their ability to sense extracellular ligands and to subsequently activate intracellular signal transduction. The integration of transmembrane receptors with transcriptional activation platforms has not yet achieved its full potential. Transient expression of plasmid DNA is often used to explore gene regulation platforms in vitro. However, applications capable of targeting therapeutically relevant endogenous or stably integrated genes are more clinically relevant. Gene regulation may allow for engineered cells to traffic into tissues of interest and secrete functional proteins into the extracellular space or to differentiate into functional cells. Transmembrane receptors that regulate transcription have the potential to revolutionize cell therapies in a myriad of applications, including cancer treatment and regenerative medicine. In this review, we will examine current engineering approaches to control transcription in mammalian cells with an emphasis on systems that can be selectively activated in response to extracellular signals. We will also speculate on the potential therapeutic applications of these technologies and examine promising approaches to expand their capabilities and tighten the control of gene regulation in cellular therapies.

Intermediate-term oncological and functional outcomes of salvage cryotherapy for the management of prostate cancer recurrence after primary brachytherapy versus primary cryotherapy: A propensity score-matched analysis.

BACKGROUND: Salvage cryotherapy (SCT) is widely used to treat prostate cancer (PCa) recurrence after radiotherapy (RT). We studied the intermediate oncological and functional outcomes of patients who underwent SCT following cryotherapy (CRYO-SCT) recurrence and compare it to recurrence after brachytherapy (BT-SCT). METHODS: An IRB-approved retrospective cohort study utilizing patient data from the Cryo On-Line Data Registry and the Duke PCa database between 1992 and 2016. Biochemical recurrence (BCR) using Phoenix criteria was the primary endpoint assessed at 2- and 5-years post-SCT. Secondary endpoints assessed functional outcomes including urinary continence, erectile function, and recto-urethral fistula. Association between treatment and biochemical progression-free survival was assessed using inverse probability weighted (IPTW) Cox proportional hazards regression. The differences in the secondary functional outcomes were assessed by Pearson's χ2 test or Fisher's exact test, corrected for IPTW. RESULTS: A total of 194 patients met inclusion criteria. The BCR rate for BT-SCT and CRYO-SCT was 23 (20.4%) and 17 (21%) at 2 years and 30 (26.5%) and 22 (27.2%) at 5 years according to Phoenix criteria. There was no statistical difference in 2 years (hazard ratio [HR] 0.9; 95% confidence interval [CI], 0.5-1.7, p = 0.7) or 5-year BCR (HR: 0.86; 95% CI, 0.5-1.5, p = 0.6) between the groups. The functional outcomes like urinary continence (p = 0.4), erectile function (p = 0.1), and recto-urethral fistula (p = 0.3) were not statistically different. CONCLUSION: CRYO-SCT appears to be well tolerated, with comparable oncological and functional outcomes to patients failing primary BT. The findings also demonstrated that SCT can render a significant number of patients biochemically free of disease after initial CRYO with minimal morbidity. SCT is a viable treatment option to salvage local PCa recurrence following either BT or cryoablation failure.

Salvage Cryoablation for Recurrent Prostate Cancer Following Primary External Beam Radiotherapy or Primary Cryotherapy: A Propensity Score Matched Analysis of Mid-term Oncologic and Functional Outcomes.

INTRODUCTION: Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT) were studied. METHODS: Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS).  Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. RESULTS: 419 XRT-SCT and 63 CRYO-SCT patients met inclusion criteria, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P = .5 and P = .7) and after matching (P = .6 and P = .3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR=1.1, [0.2-2.2]).  On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. CONCLUSION: Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy.

Structure and Function of the Mammalian Neuromuscular Junction.

The mammalian neuromuscular junction (NMJ) comprises a presynaptic terminal, a postsynaptic receptor region on the muscle fiber (endplate), and the perisynaptic (terminal) Schwann cell. As with any synapse, the purpose of the NMJ is to transmit signals from the nervous system to muscle fibers. This neural control of muscle fibers is organized as motor units, which display distinct structural and functional phenotypes including differences in pre- and postsynaptic elements of NMJs. Motor units vary considerably in the frequency of their activation (both motor neuron discharge rate and duration/duty cycle), force generation, and susceptibility to fatigue. For earlier and more frequently recruited motor units, the structure and function of the activated NMJs must have high fidelity to ensure consistent activation and continued contractile response to sustain vital motor behaviors (e.g., breathing and postural balance). Similarly, for higher force less frequent behaviors (e.g., coughing and jumping), the structure and function of recruited NMJs must ensure short-term reliable activation but not activation sustained for a prolonged period in which fatigue may occur. The NMJ is highly plastic, changing structurally and functionally throughout the life span from embryonic development to old age. The NMJ also changes under pathological conditions including acute and chronic disease. Such neuroplasticity often varies across motor unit types. © 2022 American Physiological Society. Compr Physiol 12:1-36, 2022.

Mitochondrial adaptations to inactivity in diaphragm muscle fibers.

Type I and IIa diaphragm muscle (DIAm) fibers comprise slow and fast fatigue-resistant motor units that are recruited to accomplish breathing and thus have a high duty cycle. In contrast, type IIx/IIb fibers comprise more fatigable fast motor units that are infrequently recruited for airway protective and straining behaviors. We hypothesize that mitochondrial structure and function in type I and IIa DIAm fibers adapt in response to inactivity imposed by spinal cord hemisection at C2 (C2SH). At 14 days after C2SH, the effect of inactivity on mitochondrial structure and function was assessed in DIAm fibers. Mitochondria in DIAm fibers were labeled using MitoTracker Green (Thermo Fisher Scientific), imaged in three-dimensions (3-D) by fluorescence confocal microscopy, and images were analyzed for mitochondrial volume density (MVD) and complexity. DIAm homogenate from either side was assessed for PGC1α, Parkin, MFN2, and DRP1 using Western blot. In alternate serial sections of the same DIAm fibers, the maximum velocity of the succinate dehydrogenase reaction (SDHmax) was determined using a quantitative histochemical technique. In all groups and both sides of the DIAm, type I and IIa DIAm fibers exhibited higher MVD, with more filamentous mitochondria and had higher SDHmax normalized to both fiber volume and mitochondrial volume compared with type IIx/IIb Diam fibers. In the inactive right side of the DIAm, mitochondria became fragmented and MVD decreased in all fiber types compared with the intact side and sham controls, consistent with the observed reduction in PGC1α and increased Parkin and DRP1 expression. In the inactive side of the DIAm, the reduction in SDHmax was found only for type I and IIa fibers. These results show that there are intrinsic fiber-type-dependent differences in the structure and function of mitochondria in DIAm fibers. Following C2SH-induced inactivity, mitochondrial structure (MVD and fragmentation) and function (SDHmax) were altered, indicating that inactivity influences all DIAm fiber types, but inactivity disproportionately affected SDHmax in the more intrinsically active type I and IIa fibers.NEW & NOTEWORTHY Two weeks of diaphragm (DIAm) inactivity imposed by C2SH caused reduced mitochondrial volume density, mitochondrial fragmentation, and a concomitant reduction of SDHmax in type I and IIa DIAm fibers on the lesioned side. Type I and IIa DIAm fibers were far more sensitive to inactivation than type IIx/IIb fibers, which exhibited little pathology. Our results indicate that mitochondria in DIAm fibers are plastic in response to varying levels of activity.

Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy.

Inadequate oxygen supply, or hypoxia, is characteristic of the tumor microenvironment and correlates with poor prognosis and therapeutic resistance. Hypoxia leads to the activation of the hypoxia-inducible factor (HIF) signaling pathway and stabilization of the HIF-α subunit, driving tumor progression. The homologous alpha subunits, HIF-1α and HIF-2α, are responsible for mediating the transcription of a multitude of critical proteins that control proliferation, angiogenic signaling, metastasis, and other oncogenic factors, both differentially and sequentially regulating the hypoxic response. Post-translational modifications of HIF play a central role in its behavior as a mediator of transcription, as well as the temporal transition from HIF-1α to HIF-2α that occurs in response to chronic hypoxia. While it is evident that HIF-α is highly dynamic, HIF-2α remains vastly under-considered. HIF-2α can intensify the behaviors of the most aggressive tumors by adapting the cell to oxidative stress, thereby promoting metastasis, tissue remodeling, angiogenesis, and upregulating cancer stem cell factors. The structure, function, hypoxic response, spatiotemporal dynamics, and roles in the progression and persistence of cancer of this HIF-2α molecule and its EPAS1 gene are highlighted in this review, alongside a discussion of current therapeutics and future directions.

Mitochondrial Fragmentation and Dysfunction in Type IIx/IIb Diaphragm Muscle Fibers in 24-Month Old Fischer 344 Rats.

Sarcopenia is characterized by muscle fiber atrophy and weakness, which may be associated with mitochondrial fragmentation and dysfunction. Mitochondrial remodeling and biogenesis in muscle fibers occurs in response to exercise and increased muscle activity. However, the adaptability mitochondria may decrease with age. The diaphragm muscle (DIAm) sustains breathing, via recruitment of fatigue-resistant type I and IIa fibers. More fatigable, type IIx/IIb DIAm fibers are infrequently recruited during airway protective and expulsive behaviors. DIAm sarcopenia is restricted to the atrophy of type IIx/IIb fibers, which impairs higher force airway protective and expulsive behaviors. The aerobic capacity to generate ATP within muscle fibers depends on the volume and intrinsic respiratory capacity of mitochondria. In the present study, mitochondria in type-identified DIAm fibers were labeled using MitoTracker Green and imaged in 3-D using confocal microscopy. Mitochondrial volume density was higher in type I and IIa DIAm fibers compared with type IIx/IIb fibers. Mitochondrial volume density did not change with age in type I and IIa fibers but was reduced in type IIx/IIb fibers in 24-month rats. Furthermore, mitochondria were more fragmented in type IIx/IIb compared with type I and IIa fibers, and worsened in 24-month rats. The maximum respiratory capacity of mitochondria in DIAm fibers was determined using a quantitative histochemical technique to measure the maximum velocity of the succinate dehydrogenase reaction (SDH max ). SDH max per fiber volume was higher in type I and IIa DIAm fibers and did not change with age. In contrast, SDH max per fiber volume decreased with age in type IIx/IIb DIAm fibers. There were two distinct clusters for SDH max per fiber volume and mitochondrial volume density, one comprising type I and IIa fibers and the second comprising type IIx/IIb fibers. The separation of these clusters increased with aging. There was also a clear relation between SDH max per mitochondrial volume and the extent of mitochondrial fragmentation. The results show that DIAm sarcopenia is restricted to type IIx/IIb DIAm fibers and related to reduced mitochondrial volume, mitochondrial fragmentation and reduced SDH max per fiber volume.

Utility estimation for neurogenic bowel dysfunction in the general population.

BACKGROUND: Neurogenic bowel dysfunction (NBD) affects over 80% of individuals with spina bifida causing bowel incontinence and/or constipation. NBD is also associated with decreased quality of life, depression, anxiety, and decreased employment/educational attainment. Because NBD is a life-altering condition without a cure, understanding the utility of different health states related to NBD would aid clinicians as they try to counsel families regarding management options and to better understand the quality of life associated with disease management. OBJECTIVE: To elicit utility scores for NBD using an online community sample. STUDY DESIGN: A cross-sectional anonymous survey was completed by 1534 voluntary participants via an online platform (Amazon Mechanical Turk (MTurk, http://www.mturk.com/)), representing an 87% response rate. The survey presented hypothetical scenarios that asked respondents to imagine themselves as an individual living with NBD or as the caretaker of a child with NBD. The time trade-off (TTO) method was used to estimate a utility score, and outcomes for each scenario were calculated using median and IQR. Univariate comparisons of distributions of TTO for demographic data were made using Kruskal-Wallis tests. RESULTS: The median utility score for NBD was 0.84 [0.70-0.92]. Participants reported that they would give up a median of 5 years of their own life, to prevent NBD in themselves of their child. Utility values for child scenarios were significantly different when stratified by age, gender, race, parental status, marital status, and income. Stratification by current health status did not yield significantly different utility values. DISCUSSION: Study findings are comparable with other TTO-determined utility values of moderately severe disease states, including severe persistent asthma (0.83), moderate seizure disorder (0.84) and mild mental retardation (0.84). The significant variations in utility values based on age, gender, race, parent status, partner/marital status and income variables existed in our study, which is similar to findings in other health fields. Study limitations include lack of unanimous agreement about TTO's validity in measuring utility values, and MTurk participant reports can be generalized to greater population. CONCLUSION: NBD is perceived by the community as having a substantial impact on the lives of children with spina bifida, representing a 16% reduction from perfect health. In general, health state utilities have been increasingly used in healthcare systems to understand how burdensome a population perceives a disease is and to evaluate whether interventions improve quality of life years.

Exercise with TENS does not augment gains in balance and strength for dancers.

Electrical stimulation modulates sensory feedback and improves motor performance, at least for individuals with compromised sensorimotor function. The purpose of this study was to determine the effectiveness of a 4-wk intervention with transcutaneous electrical nerve stimulation (TENS) at improving strength and balance in dancers. Nineteen dancers completed a timed, single-leg balance test, the Y-balance test, and contractions with the hip flexor and knee extensor muscles to assess maximal strength and force steadiness. They completed 4-wks of moderate-intensity bodyweight exercises (3x/wk) and were pseudo-randomized to either a Treatment or Sham group in a single-blind design. The Treatment group received constant TENS over the hamstring muscles during the exercises, whereas the Sham group was exposed to a brief TENS current. The data were pooled due to few significant between-group differences from before to after the intervention. Most outcome measures significantly improved: hip extensor muscles were stronger (P ≤ 0.01), time stood on a single-leg with eyes closed increased (P = 0.02), and the distance reached during the Y-balance test increased (P ≤ 0.001). The improvement in scores on the Y-balance test exceeded the minimal clinically significant change. Twelve sessions of moderate-intensity bodyweight exercises improved muscle strength and balance in experienced dancers. The addition of TENS, however, did not augment the gains in function.

Incidence and Predictors of 30-day Acute Cerebrovascular Accidents Post Atrial Fibrillation Catheter Ablation (From the Nationwide Readmissions Database).

Catheter-based ablation is increasingly being used as first-line therapy for atrial fibrillation (AF). Cerebrovascular accidents (CVA) are a known complication. In this study, we investigate the 30-day incidence and predictors of acute CVA postcatheter ablation for AF. The Nationwide Readmissions Database from 2010 to September 2015 was queried for hospitalizations with an ablation procedure and a concurrent AF diagnosis. The primary end point was a composite end point of CVA during index admission or readmission for CVA within 30 days of admission for index hospitalization. The associations between the incidence of end points and the covariates of interest; which included age, gender, hospital characteristics (size, procedural volume, urban/rural status, and teaching status), CHA2DS2-VASc co-morbidity score and its components was assessed using logistic regression. Appropriate survey weighting methodology was applied to generate nationally representative estimates. Of 67,090 weighted hospitalizations for AF ablation, 566 (0.8%) had CVA within 30 days post-ablation. In multivariate regression analysis, factors associated with CVA included hypertension (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.04, 1.85), heart failure (OR 4.97, 95% CI 3.32, 7.44), previous stroke/ transient ischemic attack (OR 3.25, 95% CI 2.39, 4.42) and a lower procedural volume (OR for higher procedural volume: 0.6, 95% CI 0.42, 0.85). CHA2DS2-VASc score (OR 1.27, 95% CI 1.17, 1.39) was associated with CVA in univariate analysis. In conclusion, the CVA incidence within 30-day of catheter-based AF ablation therapy was 0.8%. Higher CHA2DS2-VASc score was associated with higher risk of CVA post-ablation. Hypertension, heart failure, previous stroke/transient ischemic attack, and procedural volume were independently associated with CVA post-ablation.

The Absence of a Validated English-Language Survey to Assess Prosthesis Satisfaction: A Prospective Cohort Using the Sexual Quality of Life After Penile Prosthesis.

BACKGROUND: Prior assessments of sexual quality of life (SQoL) after penile prosthesis implantation have been performed without validated implant-specific tools. The Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire was designed and validated in Italian to specifically evaluate SQoL after a penile prosthesis is placed. AIM: We aim to better characterize prosthesis-specific SQoL after inflatable penile prosthesis placement using the English translation of the QoLSPP questionnaire. METHODS: A total of 395 consecutive patients received an inflatable penile prosthesis between January 1, 2009 and November 27, 2017, and 270 had functional emails to whom the QoLSPP questionnaire was sent. 90 surveys were completed by 75 first-time implantees and 15 patients who underwent removal/replacement surgery. Responses were considered positive if ≥ 3. Among first-time implantees, subpopulation analysis was carried out by age at survey completion (<55 years, 55-65 years, and ≥66 years), age of penile prosthesis at survey completion (<1 year, 1-5 years, and >5 years), device model (Coloplast Titan, AMS 700 CX, and AMS LGX), history of a psychiatric diagnosis, etiology of erectile dysfunction, total device length > or ≤ 21 cm, diabetes status, and body mass index < /≥ 30. Responses were analyzed in R using t-tests for continuous variables and Chi-squared tests (Fisher's for small counts) for categorical variables. OUTCOMES: The main outcome measure of this study was sexual quality of life assessed by QoLSPP. RESULTS: Patients completed the survey on average 3.15 years from their most recent prosthesis placement. 84% of first-time implantees had positive responses. Among them, there were no significant differences in the proportion of positive responses by device type, age, history of a psychiatric diagnosis, total implanted device length, etiology of erectile dysfunction, diabetes, or body mass index statuses (all P > .05). There was no difference in SQoL between first-time implantees and those who underwent removal/replacement surgery (P = 1.0). CLINICAL IMPLICATIONS: Patients experience a positive impact on their SQoL following implantation of a penile prosthesis. STRENGTHS & LIMITATIONS: Our study is the first to apply the English language QoLSPP which demonstrates high prosthesis specific SQoL but is limited by size and a lack of a validated English language tool. CONCLUSIONS: The positive impact on patients' SQoL with penile prosthesis is 84% when assessed by the English QoLSPP questionnaire. While these results mirror those reported from Italy, the English-speaking patient population is plagued with a lack of a validated tool to assess satisfaction, a void the academic and prosthetic community must fill to better understand the impact prostheses have on their patients. Carlos EC, Nosé BD, Barton GJ, et al. The Absence of a Validated English-Language Survey to Assess Prosthesis Satisfaction: A Prospective Cohort Using the Sexual Quality of Life After Penile Prosthesis. J Sex Med 2020;17:2307-2310.

Comparison of Penile Prosthesis Cultures Within Individual Patients After Removal/Replacement and Subsequent Salvage.

INTRODUCTION: Infection rates for virgin inflatable penile prostheses (IPPs) range from 1 to 3%; however, this can increase to 7-18% after IPP revision or removal/replacement (RR) for mechanical malfunction. Although studies have reported various RR and salvage cultures, limited data are available that directly compare microorganisms after each of these procedures within the same patient. Comparison of these cultures may determine if the infection is due to a persistent microorganism or new inoculation. AIM: Our aim is to characterize prosthesis cultures within individual patients who develop infection after RR. METHODS: We retrospectively reviewed patients undergoing various IPP procedures at our institution from September 2002 to August 2018. RR procedures were determined by current procedural terminology codes 54,410 or 54,416. Infection, defined as salvage or explantation without replacement for infectious reasons, was described by current procedural terminology codes 54406, 54411, 54415, or 54417. Inclusion criteria consisted of IPP infection after RR and the presence of both RR and salvage cultures within the same patient. Owing to the small cohort size, only descriptive statistics were used. MAIN OUTCOME MEASURES: Characterization of removal/replacement and salvage cultures is the main outcome measure of this study. RESULTS: A total of 202 non-infected RR procedures were performed with 9 cases (4%) of IPP infection after RR identified. Four (44%) of the RR cultures were positive and contained gram-positive (44%) and gram-negative (11%) organisms. In comparison, salvage cultures grew gram-positive bacteria (66%), gram-negative bacteria (33%), and/or fungal elements (33%). A direct comparison of the RR and salvage cultures indicated that only 2 patients (22%) grew similar organisms. CONCLUSIONS: The risk of IPP infection after RR and modified washout is low. In this small series, gram-positive bacteria were most common at the time of RR and salvage. The increased incidence of fungal infections may indicate a need to modify RR protocols. Larger multi-institutional studies are needed to further investigate this relationship. Chandrapal J, Harper S, Davis LG, et al. Comparison of Penile Prosthesis Cultures Within Individual Patients After Removal/Replacement and Subsequent Salvage. Sex Med 2020;8:783-787.

Penile Implant Infection: Experience With Expanded Salvage Criteria and a Shortened Course of Postoperative Antibiotics.

INTRODUCTION: The preferred treatment for inflatable penile prosthesis (IPP) infection includes antibiotic therapy, device removal, and immediate replacement. While this is an accepted procedure, the delivery and length of postoperative antibiotics are not standardized. Furthermore, historical salvage criteria may be overly restrictive given the new salvage techniques. AIM: Our aim is to determine if an expanded salvage criteria and shorter course of antibiotics demonstrate acceptable IPP infection rates. METHODS: We retrospectively reviewed 466 consecutive IPP cases from a single surgeon between March 2014 and March 2019. Salvage and reinfection were determined by current procedural terminology codes, and the final cohort was individually reviewed for integrity. Demographic, operative, and culture data from each patient were obtained. All patients were discharged on oral antibiotics after initial salvage. Patients were not excluded for exposed hardware, immunosuppression, tissue necrosis, severe diabetes, or corporal purulence. Owing to the small sample size, only descriptive statistics were used to describe the final cohort. MAIN OUTCOME MEASURES: The main outcome measures were classification of microorganisms cultured at the time of salvage and salvage failure rate. RESULTS: A total of 26 cases of IPP infections (6%) were identified. The median (interquartile ratio) age and body mass index were 62 (58-66) and 32 (28-34), respectively. During initial salvage, gross purulence was noted in 9 patients (35%), and 22 patients (84%) had a malleable prosthesis placed. The most prescribed postoperative antibiotic was Bactrim/Augmentin with a median (interquartile ratio) antibiotic duration of 14 days (11-14). After IPP salvage, 2 patients (8%) developed a reinfection while on oral antibiotics. One of those patients was immunosuppressed, and the other was infected with Candida glabrata. CONCLUSION: Expanded salvage criteria and postoperative oral antibiotic duration of at least 14 days demonstrated an acceptable infection rate. This suggests that a longer antibiotic therapy may not be necessary. Chandrapal J, Harper S, Davis LG, et al. Penile Implant Infection: Experience With Expanded Salvage Criteria and a Shortened Course of Postoperative Antibiotics. Sex Med 2020;8:383-387.

Cadaveric Laboratory Simulation Training of Male Stress Urinary Incontinence Treatment Improves Trainee Knowledge and Confidence.

OBJECTIVE: To assess whether a focused, simulation training course can improve trainee surgical knowledge and confidence in the treatment of male stress urinary incontinence. MATERIALS AND METHODS: Urology residents participated in a prosthetic education course as part of the 2018 SUPS and SMSNA annual meeting. The course included didactic lectures and a hands-on cadaveric laboratory. Participants completed questionnaires before and after the lab (2 weeks and 6 months) to assess procedural knowledge and confidence. Analysis of lab responses was performed using the Wilcoxon signed rank test for matched pairs. RESULTS: Thirty-two residents (median age 29, range 27-34) participated in the course. The majority were postgraduate year 4 (63%) or postgraduate year 5 (20%). Most participants reported minimal AUS or sling experience with 50% and 94% reporting less than 5 cases, respectively. Overall score from the knowledge assessment improved significantly between the pre-lab versus 2-week post-lab (P = .02) and pre-lab versus 6-month post-lab (P = .01). Similarly, procedural confidence improved between pre-lab vs 2-week post-lab (P < .001) and pre-lab versus 6-month post-lab (P < .001). Knowledge and confidence assessments were not different between year of residency training or pre-lab experience. CONCLUSIONS: Simulation training improves knowledge and confidence in prosthetic surgery for male stress incontinence. In the current climate of reduced exposure and limited availability of prosthetic educators, simulation courses can provide much needed educational value.

The Impact of Alternative Alkalinizing Agents on 24-Hour Urine Parameters.

OBJECTIVES: To determine if alternative alkalinizing agents lead to similar changes in 24-hour urine pH and citrate compared to potassium citrate (KCIT). Many stone formers cannot tolerate KCIT due to side effects or cost. In these patients, we have prescribed potassium bicarbonate or sodium bicarbonate as alternative alkali (AA), though their efficacy is unclear. METHODS: We performed a retrospective cohort study of adult stone formers seen from 2000 to 2018 with 24-hour urine analyses. Two analyses were performed. The first evaluated the alkalinizing and citraturic effects in patients with baseline low urine pH or hypocitraturia off of any alkalinizing medications, who were subsequently treated with either KCIT or AA. The second analysis compared the pH and citrate in patients changing from KCIT to an AA. Reasons for switching were abstracted by chart review and cost savings percentages were calculated using GoodRx medication prices. RESULTS: When starting alkali therapy, the median increase in pH from baseline was 0.64 for KCIT and 0.51 for AA (P = .077), and the median increase in citrate from baseline was 231 mg for KCIT and 171 mg for AA (P = .109). When switching alkali therapy, median pH and citrate did not significantly change. Hyperkalemia (24%), GI upset (19%), and cost (17%) were the most common reasons cited for switching to an AA. AA represented a savings of 86%-92% compared to KCIT. CONCLUSION: Alternative alkali appear to offer comparable improvements in 24-hour urine parameters and significant cost-savings compared to KCIT.

Force control during submaximal isometric contractions is associated with walking performance in persons with multiple sclerosis.

Individuals with multiple sclerosis (MS) experience progressive declines in movement capabilities, especially walking performance. The purpose of our study was to compare the amount of variance in walking performance that could be explained by the functional capabilities of lower leg muscles in persons with MS and a sex- and age-matched control group. Participants performed two walking tests (6-min walk and 25-ft walk), strength tests for the plantar flexor and dorsiflexor muscles, and steady submaximal (10% and 20% maximum) isometric contractions. High-density electromyography (EMG) was recorded during the steady contractions, and the signals were decomposed to identify the discharge times of concurrently active motor units. There were significant differences between the two groups in the force fluctuations during the steady contractions (force steadiness), the strength of the plantar flexor and dorsiflexor muscles, and the discharge characteristics during the steady contractions. Performance on the two walking tests by the MS group was moderately associated with force steadiness of the plantar flexor and dorsiflexor muscles; worse force steadiness was associated with poorer walking performance. In contrast, the performance of the control group was associated with muscle strength (25-ft test) and force steadiness of the dorsiflexors and variance in common input of motor units to the plantar flexors (6-min test). These findings indicate that a reduction in the ability to maintain a steady force during submaximal isometric contractions is moderately associated with walking performance of persons with MS.NEW & NOTEWORTHY The variance in walking endurance and walking speed was associated with force control of the lower leg muscles during submaximal isometric contractions in individuals with multiple sclerosis (MS). In contrast, the fast walking speed of a sex- and age-matched control group was associated with the strength of lower leg muscles. These findings indicate that moderate declines in the walking performance of persons with MS are more associated with impairments in force control rather than decreases in muscle strength.

Bone scan positivity in non-metastatic, castrate-resistant prostate cancer: external validation study

ABSTRACT Introduction: Tables predicting the probability of a positive bone scan in men with non-metastatic, castrate-resistant prostate cancer have recently been reported. We performed an external validation study of these bone scan positivity tables. Materials and Methods: We performed a retrospective cohort study of patients seen at a tertiary care medical center (1996-2012) to select patients with non-metastatic, castrate-resistant prostate cancer. Abstracted data included demographic, anthropometric, and disease-specific data such as patient race, BMI, PSA kinetics, and primary treatment. Primary outcome was metastasis on bone scan. Multivariable logistic regression was performed using generalized estimating equations to adjust for repeated measures. Risk table performance was assessed using ROC curves. Results: We identified 6.509 patients with prostate cancer who had received hormonal therapy with a post-hormonal therapy PSA ≥2ng/mL, 363 of whom had non-metastatic, castrate-resistant prostate cancer. Of these, 187 patients (356 bone scans) had calculable PSA kinetics and ≥1 bone scan. Median follow-up after castrate-resistant prostate cancer diagnosis was 32 months (IQR: 19-48). There were 227 (64%) negative and 129 (36%) positive bone scans. On multivariable analysis, higher PSA at castrate-resistant prostate cancer (4.67 vs. 4.4ng/mL, OR=0.57, P=0.02), shorter time from castrate-resistant prostate cancer to scan (7.9 vs. 14.6 months, OR=0.97, P=0.006) and higher PSA at scan (OR=2.91, P <0.0001) were significantly predictive of bone scan positivity. The AUC of the previously published risk tables for predicting scan positivity was 0.72. Conclusion: Previously published risk tables predicted bone scan positivity in men with non-metastatic, castrate-resistant prostate cancer with reasonable accuracy.