From discovery to innovation in animal health: Maturing emerging technologies for industrial development.

The Discovery to Innovation in Animal Health Conference (DIAH) was organised to bridge the gap between early developers, including academia, regulators, research organizations, and spin-offs/start-ups on one side, and medium-to large-sized companies on the other. The DIAH Conference confronted and aligned vision from academia, industry and regulators, emphasizing the need for early collaboration, careful IP management, and strategic planning for successful product development and partnerships. Recent breakthroughs in vaccinology have not only accelerated the vaccine production process but have also improved antigen quality significantly. These novel technologies are likely to transform vaccine development and play a crucial role in addressing both immediate health challenges (such as cancer vaccines) and ensuring preparedness for future pandemics. The potential and pitfalls of leveraging AI to drive forward R&I activities in the field of animal health were also discussed. Researchers and entrepreneurs looking for collaboration or investment presented a series of new technologies and start-ups, respectively. A market analysis showed that the animal health industry, while highly consolidated, also shows great diversity, ranging from big pharma to companies offering diagnostics, nutritional health services, wearables, feed additives, animal feed and genetic analyses. An analysis of the investment landscape, although subject to external factors, showed that the chances for success are high when good science, a well established regulatory pathways, with a clearly defined market need can be combined with experienced management and a strong investor consortium.

Artificial Urinary Sphincter Complications: A Narrative Review.

Stress urinary incontinence is a financially burdensome and socially isolating problem and can be experienced by men as a result of radical prostatectomy, radiation therapy, or other urologic surgery. Artificial urinary sphincter (AUS) placement for stress urinary incontinence is considered the 'gold standard' for male stress urinary incontinence. While initially only placed by specialized prosthetic surgeons, changes in urologic training have made implantation of the device by general urologists more widespread. Additionally, even though a minority of urologists place the majority of implants, many urologists may find themselves caring for patients with these devices even if they have never placed them themselves. For this reason, it is paramount that the urologic surgeon implanting the device and those caring for patients with prostheses are familiar with the various perioperative and postoperative complications of AUS implantation. This review discusses the most commonly reported complications of AUS implantation as well as those that are rarely described. Knowledge of these potential complications is necessary in order to care for patients with urologic implants.

Multipotent bone marrow cell-seeded polymeric composites drive long-term, definitive urinary bladder tissue regeneration.

To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies, including urinary diversion and bladder augmentation enterocystoplasty (BAE), utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist that need to be overcome in order to advance tissue-engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utility of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of an appropriate animal model for testing. In this study, we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold coseeded with autologous bone marrow-derived mesenchymal stem cells and CD34+ hematopoietic stem/progenitor cells support robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem-cell-seeded small-intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem-cell synergism promoted functional trilayer bladder tissue regeneration, including whole-graft neurovascularization, in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem-cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.

Rapid adoption of penoscrotal decompression for ischemic priapism in private practice.

Refractory ischemic priapism is a difficult to treat clinical entity for which there are a host of shunt procedures identified, but no singular agreed upon technique for surgical therapy. Recent literature describes success using a penoscrotal decompression technique that uses a similar dissection of a penoscrotal penile prosthesis placement. We demonstrate that this technique is easily applicable in the private practice setting as it uses a familiar setup to most general urologists in our case report.

A Prior History of Cryptozoospermia Is Associated with a Significantly Higher Chance of a Successful Microdissection Testicular Sperm Extraction Compared to Non-Obstructive Azoospermia.

BACKGROUND: Our study sought to evaluate the rates of successful sperm retrieval following microdissection testicular sperm extraction (mTESE) in patients with a prior history of cryptozoospermia, compared to patients with non-obstructive azoospermia (NOA). METHODS: A retrospective chart analysis evaluating all mTESE procedures was performed from January 2004 to August 2018. Inclusion criteria involved all males >18 years of age with a diagnosis of cryptozoospermia and/or NOA that underwent a mTESE. The patient's genetic profile, hormonal profile, semen analysis, testicular volumes, pathology and comorbidities were analyzed. RESULTS: We identified 40 patients with cryptozoospermia and 221 patients with NOA. Successful mTESE occurred in 34/40 (85%) cryptozoospermic males compared to 104/221 (48%) NOA males (p < 0.001). In univariate and multivariate analyses, patients with cryptozoospermia were more likely to undergo a successful mTESE than patients with NOA (OR 5.56 [1.79-17.29], p = 0.003; OR 5.41 [1.94-15.08], p = 0.0013), respectively. Factors that were associated with a statistically significant lower chance of successful mTESE included Sertoli-cell only pathology, pre-operative testosterone < 300 ng/dL and FSH > 7.6 mIU/mL. CONCLUSION: Despite patients with a history of cryptozoospermia having a significantly higher chance of a successful sperm retrieval than patients with NOA, couples should be counselled on the possibility of an unsuccessful sperm extraction, in order to optimize the pre-operative IVF planning and to manage operative expectations.

Regulatory policy and pharmaceutical innovation in the United Kingdom after Brexit: Initial insights.

Brexit was presented as an opportunity to promote innovation by breaking free from the European Union regulatory framework. Since the beginning of 2021 the Medicines and Healthcare products Regulatory Agency (MHRA) has operated as the independent regulatory agency for the United Kingdom. The MHRA's regulatory activity in 2021 was analyzed and compared to that of other international regulatory bodies. The MHRA remained reliant on EU regulatory decision-making for novel medicines and there were significant regulatory delays for a small number of novel medicines in the UK, the reasons being so far unclear. In addition, the MHRA introduced innovation initiatives, which show early promise for quicker authorization of innovative medicines for cancer and other areas of unmet need. Longer-term observation and analysis is needed to show the full impact of post-Brexit pharmaceutical regulatory policy.

Being Social May Be Purposeful in Older Adulthood: A Measurement Burst Design.

OBJECTIVE: Sense of purpose predicts a wide array of positive health, cognitive, and well-being outcomes during older adulthood. However, work is limited regarding how social relations correspond to purposefulness in daily life. The current study explored daily social interactions as a route to daily purposefulness in older adults, using a measurement burst design. METHODS: Older adults completed surveys for three 5-day bursts each spread 6 months apart (Mage = 70.75, SD = 7.23; N = 104). RESULTS: Multilevel models demonstrated that on days when individuals reported more positive social interactions, they reported feeling more purposeful (est. = 0.39, 95% CI [0.28, 0.51]) when accounting for health, employment, and relationship status. Employment status moderated this association, as daily social interactions were more strongly associated with daily purpose for unemployed/retired individuals (est. = -0.23, 95% CI [-0.38, -0.08]). CONCLUSION: Positive social interactions thus may help older adults maintain purposefulness, particularly after retirement.

Influence of Clinical Expertise Between Clinician-Instructors Versus Student-Instructors on the Effectiveness of Ultrasound Courses.

PURPOSE: To investigate how the extent of an ultrasound instructor's clinical expertise influences the level of hands-on ultrasound competency achieved by clinicians after three-day ultrasound courses in abdominal and emergency ultrasound. The second goal was to determine how physicians in residency rate the sonographic and didactic skills of student instructors compared to medical staff instructors. METHOD: A total of N = 100 residents participating in a 3-day ultrasound workshop were randomly trained either by 15 student instructors or by clinical staff physicians, both with > 2 years of teaching experience. Both instructor groups had previously completed 120 hours of didactic instructor training. Ultrasound competencies were assessed by a standardized objective structured clinical examination (OSCE) of healthy individuals. The sonographic and didactic skills of both instructor groups were rated by questionnaires with six-step Likert items (1 = excellent, 6 = poor). RESULTS: The cohort, trained by student instructors, achieved the same scoring level as the second cohort, trained by physician instructors (mean score 76.4, versus 73.7 of max. 100 points, p = 0.28) in the final OSCE. The sonographic qualification was rated for student educators as 1.44 (mean) [1.1-1.62], versus residents 1.46 [1.26-1.61], versus attendings 1.29 [1.05-1.61]. Didactic skill levels were rated without significant differences with means of 1.53, 1.57 and 1.53, respectively. DISCUSSION & CONCLUSION: The didactic competence of student instructors does not differ statistically from the competency levels of experienced physicians. In terms of the acquired ultrasound skills of trainees, our data indicate that student instructors can be as efficient as staff instructors. Therefore, student instructors can be employed as resource-saving ultrasound educators without decreasing the skills level achieved by course participants, provided that they previously underwent a comprehensive didactic and sonographic training program.

Prior Placement of Male Urethral Slings Can Increase the Need for Revision of Artificial Urinary Sphincters.

BACKGROUND: Recurrent stress urinary incontinence (SUI) following male sling can be managed surgically with artificial urinary sphincter (AUS) insertion. Prior small, single-center retrospective studies have not demonstrated an association between having failed a sling procedure and worse AUS outcomes. The aim of this study was to compare outcomes of primary AUS placement in men who had or had not undergone a previous sling procedure. METHODS: A retrospective review of all AUS devices implanted at a single academic center during 2000-2018 was performed. After excluding secondary AUS placements, revision and explant procedures, 135 patients were included in this study, of which 19 (14.1%) patients had undergone prior sling procedures. RESULTS: There was no significant difference in demographic characteristics between patients undergoing AUS placement with or without a prior sling procedure. Average follow up time was 28.0 months. Prior sling was associated with shorter overall device survival, with an increased likelihood of requiring revision or replacement of the device (OR 4.2 (1.3-13.2), p = 0.015) as well as reoperation for any reason (OR 3.5 (1.2-9.9), p = 0.019). While not statistically significant, patients with a prior sling were more likely to note persistent incontinence at most recent follow up (68.8% vs. 42.7%, p = 0.10). CONCLUSIONS: Having undergone a prior sling procedure is associated with shorter device survival and need for revision or replacement surgery. When considering patients for sling procedures, patients should be counseled regarding the potential for worse AUS outcomes should they require additional anti-incontinence procedures following a failed sling.

Revisiting One-Stage Urethroplasties for Distal Urethral Strictures.

BACKGROUND: Reconstructive approaches for distal urethral strictures range from simple meatotomy to utilizing grafts or flaps depending on the etiology, length and location. We describe a contemporary cohort of distal urethral strictures and report a surgical technique termed distal one-stage urethroplasty developed to address the majority of distal urethral strictures encountered. METHODS: Thirty-four patients were included. The mean age was 56.7 years (range 15.7-84.9 years), the mean stricture length was 1.1 cm (0.5-1.5) and the mean follow-up was 42.5 months (28-61.3). RESULTS: The vast majority of distal strictures (27/34 (79.4%)) were treated with our hybrid one-stage approach combining a distal urethral reconstruction with excision of the scar tissue without the need to use grafts or flaps. The average stricture length was 0.68 cm and average operative time was 24.43 min. Post-operative spraying was reported in a minority of patients (4/27 (14.8%)). The length of stricture and surgery were significantly longer in those 7/34 (20.6%) patients in whom grafts or flaps were used (2.88 cm and 154.8 min, respectively, p < 0.001 for both when compared to the hybrid one-stage approach). We noted 6/34 (17.6%) recurrences of distal urethral strictures, all of which were treated successfully with graft and flap repairs. CONCLUSIONS: The vast majority of distal urethral strictures are amenable to a distal one-stage urethroplasty, avoiding the use of grafts and/or flaps while achieving reasonable outcomes. This limited approach, at least initially, is associated with shorter operative time and time of catheter placement and avoids morbidity associated with graft or flap harvesting. Spraying of urine is seldomly encountered and comparable to other approaches addressing distal urethral strictures.

Narrative review of penile distal urethroplasties and suggestions for optimizing outcomes.

Distal urethral strictures can be a challenging entity for urologists. Endoscopic maneuvers such as optical internal urethrotomies or dilations are even less successful than in other urethral locations and the repeated trauma will increase the scarring which advocates for a urethroplasty as primary option for patient management. Success rates of distal urethroplasties have been lower than those for other urethral strictures due to the anatomy of the distal urethra with a very thin corpus spongiosum associated with decreased mucosal blood supply. Also, the high prevalence of lichen sclerosus in this population with circumferential scarring is often a complicating factor. However, in the past two decades several surgical techniques have been described and further developed which has led to significant improvement in stricture recurrence rates. Meatoplasties are indicated for strictures limited to the meatus and involve opening of the stenotic meatus with subsequent reconstruction of it to minimize spraying of urine. Often, however, distal urethral strictures involve the fossa navicularis and may even extend further proximally. These strictures can be addressed with dorsal or ventral inlay procedures using buccal mucosa graft. In addition or alternatively, skin flaps can be mobilized to increase the urethral diameter. Lastly, multi-stage urethroplasty with buccal mucosa are a very successful approach yet given the high success rates of above mentioned procedures are usually reserved for revision surgery or most severe distal urethral strictures. In the following report, we are describing a variety of surgical techniques and their indication which should allow the practicing urologist to successfully address all encountered distal urethral strictures.

A Vision-Based Sensing Approach for a Spherical Soft Robotic Arm.

Sensory feedback is essential for the control of soft robotic systems and to enable deployment in a variety of different tasks. Proprioception refers to sensing the robot's own state and is of crucial importance in order to deploy soft robotic systems outside of laboratory environments, i.e. where no external sensing, such as motion capture systems, is available. A vision-based sensing approach for a soft robotic arm made from fabric is presented, leveraging the high-resolution sensory feedback provided by cameras. No mechanical interaction between the sensor and the soft structure is required and consequently the compliance of the soft system is preserved. The integration of a camera into an inflatable, fabric-based bellow actuator is discussed. Three actuators, each featuring an integrated camera, are used to control the spherical robotic arm and simultaneously provide sensory feedback of the two rotational degrees of freedom. A convolutional neural network architecture predicts the two angles describing the robot's orientation from the camera images. Ground truth data is provided by a motion capture system during the training phase of the supervised learning approach and its evaluation thereafter. The camera-based sensing approach is able to provide estimates of the orientation in real-time with an accuracy of about one degree. The reliability of the sensing approach is demonstrated by using the sensory feedback to control the orientation of the robotic arm in closed-loop.

Effects of Anti-Inflammatory Nanofibers on Urethral Healing.

Protracted postsurgical inflammation leading to postoperative complications remains a persistent problem in urethral reconstruction. Nanofibers in the form of peptide amphiphiles expressing anti-inflammatory peptides (AIF-PA) have positively modulated local inflammatory responses. Urethroplasty is performed to repair 5 mm ventral urethral defects with: uncoated small intestinal submucosa (SIS); SIS dip-coated with AIF-PA1 (anti-inflammatory treatment), or SIS dip-coated with AIF-PA6 (control) on 12-week-old male Sprague Dawley rats (n = 6/group/timepoint). Animals are euthanized at 14 and 28 d postsurgery. Hematoxylin-eosin, Masson's Trichrome, and immunohistochemistry with primary antibodies against myeloperoxidase (MPO; neutrophils), CD68, CD86, CD206 (macrophages), and proinflammatory cytokines TNFα and IL-1ß are performed. Complete urethral healing occurs in 3/6 uncoated SIS (50%), 2/6 SIS+AIF-PA6 (33.3%), and 5/6 SIS+AIF-PA1 (83.3%) animals at 14 d and all at 28 d. Application of AIF-PA1 to SIS substitution urethroplasty decreases MPO+ neutrophils, CD86+ M1 proinflammatory macrophages, TNFα, and IL-1ß levels while concurrently increasing levels of CD206+ M2 proregenerative/anti-inflammatory macrophages at the anastomoses and the regenerated tissue at the wound bed (REGEN). AIF-PA1 treatment enhances the healing process, contributing to earlier, complete urethral healing, and increased angiogenesis. Further studies are needed to elucidate the specific mechanism of inflammatory response modulation on angiogenesis and overall urethral healing.

Testosterone and Estrogen Repletion in a Hypogonadal Environment Improves Post-operative Angiogenesis.

OBJECTIVE: To determine the effects of perioperative hormone supplementation on postoperative periurethral angiogenesis in the setting of hypogonadism, we analyzed the urethral tissue of castrated Sprague Dawley rats supplemented with testosterone or estrogen who underwent a urethral surgery and compared it to those that did not. MATERIALS AND METHODS: 48 Sprague-Dawley rats were divided into 4 groups: (1) non-castrate (NC) controls; (2) castrate (C) unsupplemented rats; (3) castrate rats that received testosterone (T), or (4) castrate rats that received estradiol (E). Half of each group underwent urethroplasty surgery (S) while the other half were nonsurgical controls (C). With immunohistochemistry, we measured vessel density (endothelial cell marker CD31), expression levels of androgen receptor (AR), TIE-2, and estrogen receptor GPER1. RESULTS: Periurethral vascularity was significantly increased postoperatively with both testosterone and estrogen supplementation (TC vs TS: 8.92% vs 10.80%, P<.001; EC vs ES: 7.66 vs 8.73%, P = .009) as well as in noncastrated rats (NCC vs NCS: 5.86% vs 8.19%, P<.001) whereas in the absence of hormones, CD31 expression significantly decreased after surgery (CC vs CS: 3.62% vs 2.76%, P= .003). CD31 expression was strongly correlated with AR, TIE-2, and GPER1 expression indicating a mechanistic relationship. CONCLUSION: Both testosterone and estrogen supplementation increase periurethral vascularity in castrated (hypogonadal) rats undergoing urethroplasty surgery, contrary to decreased periurethral vascularity observed in the castrated non-supplemented rats. This suggests that hormonal resupplementation benefits post-operative regeneration in rats and may provide a basis for perioperative hormone supplementation in hypogonadal men prior to urethral surgery.

Evaluation of Opioid Prescribing Patterns and Drivers of Variation Following Endoscopic Procedures for Benign Prostatic Hyperplasia Across an Integrated Academic Health System.

OBJECTIVES: To evaluate patient, provider, and facility factors associated with variation in opioid prescribing after endoscopic procedures for benign prostatic hyperplasia across a large academic health system to drive improvement efforts. METHODS: Opioids prescribed at discharge for patients who underwent an endoscopic prostate procedure March 2018-November 2019 were analyzed. Multivariable logistic and linear regression were used to evaluate the relationship between patient, provider, and facility factors and the receipt of any opioid prescription and the quantity prescribed. RESULTS: We included 724 patients who had surgery with one of 26 urologists across five facilities. 222 (30.7%) received an opioid prescription, and the average morphine milligram equivalents (MMEs) prescribed was 97.9±33.5. We found wide variation in the proportion of patients who received an opioid prescription across surgeons (range 0%-88.9%) and facilities (range 19.9%-66.7%) and the average MMEs prescribed (range 25-188.5). Outpatient surgery (OR 2.32; 95% confidence interval [CI] 1.22-4.40, P = .010) and preoperative opioid use (OR 15.04; CI 9.65-23.45, P < .001) were associated with higher rates of opioid prescribing, while prescribing decreased with increasing patient age (OR 0.97; CI 0.95-0.99, P = 0.016). Multivariable linear regression analysis demonstrated an association between surgery at satellite facilities, having a surgeon in practice for at least 20 years, and higher surgeon volume with increased MMEs prescribed. CONCLUSIONS: Opioid prescribing following endoscopic prostate procedures varied widely. Targeted interventions tailored to younger patients, those taking opioids preoperatively, recipients of outpatient surgery and those undergoing surgery at satellite facilities may be particularly high yield given the association between these factors and increased postoperative prescribing.

Revisiting the penoscrotal approach to artificial urinary sphincter surgery: how does it compare to a perineal incision for initial implantation?

PURPOSE: Artificial urinary sphincters (AUS) remain the gold standard to treat male stress urinary incontinence. AUS implantation can be performed through a penoscrotal or perineal incision depending on surgeon preference. METHODS: The present study compares initial AUS implantation through two surgical approaches focusing on outcomes of continence and revision. All AUS implanted at an academic medical center between 2000 and 2018 were retrospectively reviewed. RESULTS: A total of 225 AUS implantations were identified, of which, 114 patients who underwent virgin AUS placement were included in the study with a mean follow-up of 28.5 months. A total of 68 patients (59.6%) had AUS placement through penoscrotal incision; while, 46 (40.4%) had a perineal incision. While operative time was significantly shorter for penoscrotal placement (98.6 min vs. 136.3 min, p = 0.001), there were no significant differences in continence rates between either surgical approach with 76.5% socially continent defined as using zero to less than 1 pad per day (safety pad). The overall rate of device erosion or infection was not significantly different between groups. However, the rate of revision or replacement was significantly higher in the perineal group (26.1% v. 8.8%; p = 0.01). On multivariate analysis, the penoscrotal incision predicted a lower rate of device revision (p = 0.01). CONCLUSIONS: The penoscrotal approach of AUS placement is associated with shorter operative time. While we observed a lower revision rate compared to the perineal approach, there were equivalent continence outcomes.