Preclinical applications of high-definition manometry system to investigate pelvic floor muscle contribution to continence mechanisms in a rabbit model.

External anal sphincter (EAS), external urethral sphincters, and puborectalis muscle (PRM) have important roles in the genesis of anal and urethral closure pressures. In the present study, we defined the contribution of these muscles alone and in combination with the sphincter closure function using a rabbit model and a high-definition manometry (HDM) system. A total of 12 female rabbits were anesthetized and prepared to measure anal, urethral, and vaginal canal pressures using a HDM system. Pressure was recorded at rest and during electrical stimulation of the EAS and PRM. A few rabbits (n = 6) were subjected to EAS injury and the impact of EAS injury on the closure pressure profile was also evaluated. Anal, urethral, and vaginal canal pressures recorded at rest and during electrical stimulation of EAS and PRM demonstrated distinct pressure profiles. EAS stimulation induced anal canal pressure increase, whereas PRM stimulation increased the pressures in all the three orifices. Electrical stimulation of EAS after injury resulted in about 19% decrease in anal canal pressure. Simultaneous electrical stimulation of EAS and PRM resulted in an insignificant increase of individual anal canal pressures when compared with pressures recorded after EAS or PRM stimulations alone. Our data confirm that HDM is a viable system to measure dynamic pressure changes within the three orifices and to define the role of each muscle in the development of closure pressures within these orifices in preclinical studies.NEW & NOTEWORTHY We anticipate that with this new HDM technology, physiological changes within these orifices may be redefined using the extensive data that are generated from 96 sensors. When compared with conventional methods, HDM offers the advantages of an increased response rate, as well as the utilization of 96 circumferential sensors to simultaneously measure pressure along the three orifices. Our findings suggest a potential use of this technology to better define urinary leak point pressure.

Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction.

PURPOSE: Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a non-invasive intervention for ED, but its effect on penile microvascular function, remains unclear. Our objectives are to (i) evaluate the effect of Li-ESWT (specifically radial type ESWT [rESWT]) on penile microvascular perfusion (PMP) in aging rats, (ii) elucidate a possible mechanism, and (iii) evaluate its impact on angiogenic and smooth muscle biomarkers in cavernosal tissue. MATERIALS AND METHODS: Male rats (n=9; 15-18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. Rats were euthanized at the end of the study and penile tissues were analyzed for angiogenic markers (vascular endothelial growth factor-A [VEGF-A], endothelial nitric oxide synthase [eNOS]) and smooth muscle content (α-actin) using immunostaining, Western blot, and quantitative polymerase chain reaction (qPCR). RESULTS: rESWT resulted in more than a 2-fold increase in PMP (from 68.5 arbitrary units; 163.7 AU). L-NAME injection produced a <40%-50% decrease (185.3 to 101.0 AU) in rESWT-induced PMP response. Immunostaining revealed increased α-actin, eNOS, and VEGF-A in the cavernosum and these findings were confirmed by qPCR and Western blot results. CONCLUSIONS: rESWT improved PMP, which may be mediated via increased VEGF expression, which stimulates the NO/cyclic guanosine monophosphate pathway, resulting in sustained PMP. rESWT devices could offer a safe, non-invasive treatment for age-related ED.

High-Risk Patients Undergoing Holmium Laser Enucleation of the Prostate Have Fewer Infections with a Longer Course of Preoperative Antibiotics.

Introduction: There are minimal data to guide antibiotic management of patients undergoing holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia. Specifically, management of high-risk patients who are catheter dependent or have positive preoperative urine cultures varies widely. We aimed to evaluate the effect of preoperative antibiotic duration on infectious complications in high-risk patients undergoing HoLEP. Methods: A multi-institutional retrospective review of patients undergoing HoLEP between 2018 and 2023 at five institutions was performed. Patients were defined as high risk if they were catheter-dependent (indwelling urethral catheter, self-catheterization, or suprapubic tube) or had a positive preoperative urine culture. These patients were categorized into long course (>3 days) or short course (≤3 days) of preoperative antibiotics. The primary outcome was 30-day infectious complications defined as a positive urine culture with symptoms. A t-test or Wilcoxon rank-sum test was used for continuous variables and Fisher's exact test was used for categorical variables. Logistic regression analysis was conducted to identify associations with infectious complications. Results: Our cohort included 407 patients, of which 146 (36%) and 261 (64%) were categorized as short course and long course of preoperative antibiotics, respectively. Median preoperative antibiotic duration was 1 day (interquartile range [IQR]: 0, 3 days) and 7 days (IQR: 5, 7 days) in the short and long cohorts, respectively. Thirty-day postoperative infectious complications occurred in 11 (7.6%) patients who received a short course of antibiotics and 5 (1.9%) patients who received a long course of antibiotics (odds ratio 0.24, 95% confidence interval 0.07-0.67; p = 0.009). Variables such as age, positive urine culture, and postoperative antibiotic duration were not significantly associated with postoperative infection after propensity score weighting. Conclusion: In high-risk patients undergoing HoLEP, infectious complications were significantly lower with a long course vs short course of antibiotics. Further prospective trials are needed to identify optimal preoperative antibiotic regimens.

Extracorporeal Shockwave Therapy Alleviates Inflammatory Pain by Down-Regulating NLRP3 Inflammasome in Experimental Chronic Prostatitis and Chronic Pelvic Pain Syndrome.

PURPOSE: To evaluate the anti-inflammatory and antioxidative effects of extracorporeal shockwave therapy (ESWT) on prostatitis and explore the mechanism of alleviating pain. MATERIALS AND METHODS: For in vitro testing, RWPE-1 cells were randomly divided into 5 groups: (1) RWPE-1 group (normal control), (2) LPS group (lipopolysaccharide inducing inflammation), (3) 0.1ESWT group (treated by 0.1 mJ/mm² energy level), (4) 0.2ESWT group (treated by 0.2 mJ/mm² energy level), and (5) 0.3ESWT group (treated by 0.3 mJ/mm² energy level). After ESWT was administered, cells and supernatant were collected for ELISA and western blot. For in vivo testing, Sprague-Dawley male rats were randomly divided into 3 groups: (1) normal group, (2) prostatitis group, and (3) ESWT group (n=12 for each). Prostatitis was induced by 17 beta-estradiol and dihydrotestosterone (DHT) administration. Four weeks after ESWT, the pain index was assessed for all groups and prostate tissues were collected for immunohistochemistry, immunofluorescence, apoptosis analysis and, western blot. RESULTS: Our in vitro studies showed that the optimal energy flux density of ESWT was 0.2 mJ/mm². In vivo, ESWT ameliorated discomfort in rats with prostatitis and inflammation symptoms were improved. Compared to normal rats, overexpressed NLRP3 inflammasomes triggered apoptosis in rats with prostatitis and this was improved by ESWT. TLR4-NFκB pathway was overactive after experimental prostatitis, compared to normal and ESWT groups, and prostatitis induced alterations in BAX/BAK pathway were inhibited by ESWT. CONCLUSIONS: ESWT improved CP/CPPS by reducing NLRP3 inflammasome and ameliorated apoptosis via inhibiting BAX/BAK pathway in a rat model. TLR4 may play a key role in bonding NLRP3 inflammasome and BAX/BAK pathways. ESWT might be a promising approach for the treatment of CP/CPPS.

Modafinil Therapy and Mental Status Following Aneurysmal Subarachnoid Hemorrhage: Comprehensive Stroke Center Analysis.

BACKGROUND: Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. METHODS: Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. RESULTS: Modafinil (100-200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4-16) days and initiated 14 (7-17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. -0.2 [6.32], P = 0.003). CONCLUSIONS: A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting.

A Comparative Analysis between Flexible Ureteroscopic Lithotripsy and Tubeless Percutaneous Nephrolithotomy in the Treatment of >15 mm Non-Obstructing Proximal Ureteral Stones.

BACKGROUND: The proper surgical modality for large non-obstructing proximal ureteral stones is disputed. We compare effectiveness and safety of flexible ureteroscopic lithotripsy (FURL) and tubeless percutaneous nephrolithotomy (TPNL) in treatment of upper ureteral stones larger than 1.5 cm. METHODS: We reviewed the medical records of patients who performed FURL or TPNL for upper ureteral stones between June 2016 and November 2018. Comparative analysis was conducted regarding demographic parameters, stone free rate, postoperative pain and complications. RESULTS: This study included 58 patients treated with FURL and 60 patients treated with TPNL owing to upper ureteral stones larger than 1.5 cm. Stone size was similar in the FURL and TPNL groups (17.6 ± 2.6 vs. 18.0 ± 2.1 mm, p = 0.194). The overall 3-month stone clearance rate was 95.8% for FURL versus 96.0% for TPNL (p = 0.575). There was no difference between the FURL and TPNL groups for hospital stay (p = 0.280) and postoperative complications. On the other hand, patients treated with FURL had longer operative time (p = 0.012) and less postoperative pain (p = 0.008). CONCLUSIONS: Both surgical techniques were considered feasible and effective surgical procedures in the treatment of large upper ureteral stones.

Are hemostatic agents for selective cases of tubeless percutaneous nephrolithotomy necessary for access tract control? A randomized control trial.

PURPOSE: To evaluate the efficacy of percutaneous nephrolithotomy (PCNL) access tract sealing agent. Fibrin glue and Tachosil® were used for sealing the access tract and compared to the control. Post operative computed tomography (CT) scan was used to evaluate those efficacies. METHODS: A total of 108 patients were randomized to three groups: In group 1, the access tract was sutured, and compressive dressing was done. In group 2, the fibrin glue was injected into the access tract with a tip applicator at the end of operation. And group 3, Tachosil® was rolled on its longitudinal axis and plugged into the access tract. Non-contrast CT at POD 1 was taken and perirenal hematoma thickness was measured and graded. Hemoglobin, hematocrit, VAS score, stone-free status, and hospital stay were analyzed. RESULTS: Preoperative demographic differences were not significant in all three arms. Postoperative CT scans in all groups demonstrated mostly minimal grade access tract hematomas. Mean perirenal hematoma thickness showed no significant differences (2.66 ± 3.74, 2.73 ± 3.85, 2.54 ± 4.37 mm, p = 0.981), respectively. Postoperative hemoglobin drop (0.75 ± 0.58, 0.84 ± 0.47, 0.91 ± 0.60 g/dl, p = 0.74), stone-free rate (93.75, 87.87, 87.87%, p = 0.121), VAS (p = 0.499) and hospital stay (1.81 ± 0.84, 1.48 ± 0.71, 1.59 ± 0.75 day, p = 0.127) were not significantly different between the groups. CONCLUSION: Fibrin glue and Tachosil® in tubeless PCNL were not necessary for postoperative access tract control.

Socioeconomic Drivers of Outcomes After Aneurysmal Subarachnoid Hemorrhage Treatment at a Large Comprehensive Stroke Center.

BACKGROUND: Sparse data exist on socioeconomic disparities among patients treated for aneurysmal subarachnoid hemorrhage (aSAH). The authors analyzed factors possibly influencing patient outcomes, including having a primary care physician (PCP) at admission, family/caregiver support, a foreign language barrier, primary payer status, and race. METHODS: Socioeconomic data were abstracted for patients treated endovascularly or microsurgically for aSAH at a single center (January 1, 2014-July 31, 2019). Binary logistic regression analyses were used to identify independent predictors of an unfavorable outcome (modified Rankin Scale [mRS] score >2) and for predictive modeling. RESULTS: Among 422 patients, the median (interquartile range) follow-up was 2 (1-23) months. Lack of caregiver support was the only socioeconomic factor associated with an unfavorable outcome at discharge. Independent predictors of mRS score >2 at last follow-up included baseline markers of disease severity (P ≤ 0.03), nonwhite race (OR, 1.69; P = 0.047), lack of caregiver support (OR, 5.55; P = 0.007), and lack of a PCP (OR, 1.96; P = 0.007). Adjusting for follow-up mediated the effects of race and PCP, although caregiver support remained significant and PCP was associated with a lower mortality risk independent of follow-up (OR, 0.51; P = 0.047). Predischarge socioeconomic factors, alongside disease severity, predicted a follow-up mRS score >2 with excellent discrimination (area under the receiver operating curve, 0.81; 95% CI, 0.77-0.86). CONCLUSIONS: At a large, urban, comprehensive stroke center, patients with PCPs, caregiver support, and white race had significantly better long-term outcomes after aSAH. These results reflect disparities in access to healthcare after aSAH for vulnerable populations with extensive lifetime needs.

Transpelvic Magnetic Stimulation Enhances Penile Microvascular Perfusion in a Rat Model: A Novel Interventional Strategy to Prevent Penile Fibrosis after Cavernosal Nerve Injury.

PURPOSE: Penile microvascular dysfunction is a known contributor to erectile dysfunction (ED) and penile fibrosis has been shown to impair microvascular perfusion (MVP). Our objectives were to: (i) determine beneficial effects of TPMS to modulate penile MVP, (ii) determine its mechanism, (iii) evaluate impact of cavernosal nerve injury (CNI) on penile MVP, and (iv) determine time-course of cavernosal tissue elastin changes after CNI in rats. MATERIALS AND METHODS: Adult male rats (n=5) were anesthetized and subjected to TPMS (13%, 15%, and 17%) and MVP changes were recorded using laser speckle contrast imaging (LSCI). Another group of male rats were subjected to either bilateral cavernosal nerve injury (CNI; n=7) or sham surgery (n=7). After recovery, animals were monitored for MVP using LSCI before and after TPMS. Rat penile tissues were harvested and analyzed for fibrosis using a marker for elastin. RESULTS: Rat TPMS resulted in a stimulus dependent increase in MVP; maximal perfusion was observed at 17%. L-N(G)-Nitroarginine methyl ester (L-NAME) resulted in a marked decrease in TPMS induced MVP increase (393.33 AU vs. 210.67 AU). CNI resulted in 40% to 50% decrease in MVP. CNI produced a remarkable increase in elastin deposits that are noticeable throughout the cavernosal tissues post injury. CONCLUSIONS: TPMS is a novel and non-invasive intervention to improve penile MVP after CNI. Potential application includes treatment of ED and sexual function preservation following cancer treatment, possibly through improved penile hemodynamics that might help prevent penile hypoxia and fibrosis.

Evaluation of Age- and Radical-Prostatectomy Related Changes in Male Pelvic Floor Anatomy Based on Magnetic Resonance Imaging and 3-Dimensional Reconstruction.

PURPOSE: Puborectalis muscles (PRM) and ischiocavernosus muscles (ICM) play important roles in urinary continence and male erectile functions. Understanding of anatomy and surgical-injury related changes to these muscles is critical to monitor changes in continence or erectile function. Anatomical description of these muscles has undergone revisions because these conclusions were derived from cadavers. Our objectives were to: (i) elucidate male pelvic muscles by in-vivo magnetic resonance imaging (MRI) and 3-dimensional (3-D) reconstruction of these images and (ii) compare PRM and ICM thickness in healthy volunteers and symptomatic patients. MATERIALS AND METHODS: Healthy young male (mean age, 25 years; n=5), older male (age, 65-70 years; n=5), and post-prostatectomy patients with erectile dysfunction and urinary incontinence (age, 65-70 years; n=5) were scanned on a 3T-magnetic resonance scanner. Images were acquired from slices above urinary bladder base to urethra entry into penis. Pelvic bone, bladder/urethra, corpus cavernosum, ICM, PRM, and prostate were segmented. 3-D models of each structure were generated and assembled into composite images, and ICM and PRM thicknesses were calculated. RESULTS: We successfully reconstructed 3-D male pelvic floor anatomy including ICM, PRM, bladder, urethra, bulbospongiosus, corpus cavernosa, prostate and bones from the two groups. We documented significant reduction in PRM and ICM thickness in older men. CONCLUSIONS: This is perhaps the first 3-D reconstruction of male pelvic floor structures based on in-vivo MRI in healthy and symptomatic patients. Observed reduction in PRM and ICM thickness is possibly due to age-related atrophy.

Acceptability of Bedside Resuscitation With Intact Umbilical Cord to Clinicians and Patients' Families in the United States.

BACKGROUND: While delayed umbilical cord clamping in preterm infants has shown to improve long-term neurological outcomes, infants who are thought to need resuscitation do not receive delayed cord clamping even though they may benefit the most. A mobile resuscitation platform allows infants to be resuscitated at the mother's bedside with the cord intact. The newborn is supplied with placental blood during the resuscitation in view of the mother. The objective of the study is to assess the usability and acceptability of mobile resuscitation platform, LifeStart trolley, among the infants' parents and perinatal providers. METHODS: A resuscitation platform was present during every delivery that required advanced neonatal providers for high-risk deliveries. Perinatal providers and parents of the infants were given a questionnaire shortly after the delivery. RESULTS: 60 neonatal subjects were placed on the trolley. The majority of deliveries were high risk for meconium-stained amniotic fluid (43%), and non-reassuring fetal heart rate (45%). About 50% of neonatal providers felt that there were some concerns regarding access to the baby. No parents were uncomfortable with the bedside neonatal interventions, and most parents perceived that communication was improved because of the proximity to the care team. CONCLUSION: Bedside resuscitation with umbilical cord intact through the use of a mobile resuscitation trolley is feasible, safe, and effective, but about half of the perinatal providers expressed concerns. Logistical issues such as improved space management and/or delivery setup should be considered in centers planning to perform neonatal resuscitation with an intact cord.