Sialic acids in infection and their potential use in detection and protection against pathogens.

In structural terms, the sialic acids are a large family of nine carbon sugars based around an alpha-keto acid core. They are widely spread in nature, where they are often found to be involved in molecular recognition processes, including in development, immunology, health and disease. The prominence of sialic acids in infection is a result of their exposure at the non-reducing terminus of glycans in diverse glycolipids and glycoproteins. Herein, we survey representative aspects of sialic acid structure, recognition and exploitation in relation to infectious diseases, their diagnosis and prevention or treatment. Examples covered span influenza virus and Covid-19, Leishmania and Trypanosoma, algal viruses, Campylobacter, Streptococci and Helicobacter, and commensal Ruminococci.

Radiation induces long-term muscle fibrosis and promotes a fibrotic phenotype in fibro-adipogenic progenitors.

BACKGROUND: Radiation-induced muscle pathology, characterized by muscle atrophy and fibrotic tissue accumulation, is the most common debilitating late effect of therapeutic radiation exposure particularly in juvenile cancer survivors. In healthy muscle, fibro/adipogenic progenitors (FAPs) are required for muscle maintenance and regeneration, while in muscle pathology FAPs are precursors for exacerbated extracellular matrix deposition. However, the role of FAPs in radiation-induced muscle pathology has not previously been explored. METHODS: Four-week-old Male CBA or C57Bl/6J mice received a single dose (16 Gy) of irradiation (IR) to a single hindlimb with the shielded contralateral limb (CLTR) serving as a non-IR control. Mice were sacrificed 3, 7, 14 (acute IR response), and 56 days post-IR (long-term IR response). Changes in skeletal muscle morphology, myofibre composition, muscle niche cellular dynamics, DNA damage, proliferation, mitochondrial respiration, and metabolism and changes in progenitor cell fate where assessed. RESULTS: Juvenile radiation exposure resulted in smaller myofibre cross-sectional area, particularly in type I and IIA myofibres (P < 0.05) and reduced the proportion of type I myofibres (P < 0.05). Skeletal muscle fibrosis (P < 0.05) was evident at 56 days post-IR. The IR-limb had fewer endothelial cells (P < 0.05) and fibro-adipogenic progenitors (FAPs) (P < 0.05) at 56 days post-IR. Fewer muscle satellite (stem) cells were detected at 3 and 56 days in the IR-limb (P < 0.05). IR induced FAP senescence (P < 0.05), increased their fibrogenic differentiation (P < 0.01), and promoted their glycolytic metabolism. Further, IR altered the FAP secretome in a manner that impaired muscle satellite (stem) cell differentiation (P < 0.05) and fusion (P < 0.05). CONCLUSIONS: Our study suggests that following juvenile radiation exposure, FAPs contribute to long-term skeletal muscle atrophy and fibrosis. These findings provide rationale for investigating FAP-targeted therapies to ameliorate the negative late effects of radiation exposure in skeletal muscle.

Improving Patient Experience Scores Using Simultaneous Interpretation on Family-Centered Rounds.

OBJECTIVES: Patients speaking a primary language other than English face barriers to equitable care, particularly patient-provider communications. There is no gold standard for providing inpatient medical interpretation on family-centered rounds (FCR). We aimed to implement simultaneous, in-person interpretation of FCR for Spanish-speaking families and hypothesized improved satisfaction in care. METHODS: In-person, Spanish Equipment-Assisted Simultaneous Medical Interpretation (EASMI) was implemented in March 2018 on FCR. Child Hospital Consumer Assessment of Healthcare Providers and Systems (Child HCAHPS) experience scores on communication domains were analyzed for Spanish and English-speaking families pre- (n = 118) and postimplementation (n = 552). Postimplementation, we conducted medical team surveys (n = 104) and semistructured interviews with Spanish-speaking families (n = 25) to determine satisfaction with interpretation modalities (phone, video, and EASMI). RESULTS: Spanish-speaking families exhibited statistically significant improvements in Child HCAHPS top box scores compared to English-speaking families in multiple communication and informed care-related domains. For example, "How often did your child's doctors explain things to you in a way that was easy to understand?" top box scores improved from 58% to 95% for Spanish-speaking families, compared to 85% to 83% for English speakers, with the differential effect of the intervention showing statistical significance (P = .001). Medical team surveys demonstrated high satisfaction with EASMI. Qualitative themes from interviews and open-ended survey responses emphasized multiple care benefits with EASMI, including a perceived reduction of communication errors and increased family participation. CONCLUSIONS: EASMI was associated with significant improvements in Child HCAHPS scores in communication domains and increased medical team and family members' satisfaction with interpretation. EASMI presents a novel method for equitable FCR for Spanish-speaking families.

Social distancing causally impacts the spread of SARS-CoV-2: a U.S. nationwide event study.

We assess the causal impact of social distancing on the spread of SARS-CoV-2 in the U.S. using the quasi-natural experimental setting created by the spontaneous relaxation of social distancing behavior brought on by the protests that erupted across the nation following George Floyd's tragic death on May 25, 2020. Using a difference-in-difference specification and a balanced sample covering the [- 30, 30] day event window centered on the onset of protests, we document an increase of 1.34 cases per day, per 100,000 population, in the SARS-CoV-2 incidence rate in protest counties, relative to their propensity score matching non-protest counterparts. This represents a 26.8% increase in the incidence rate relative to the week preceding the protests. We find that the treatment effect only manifests itself after the onset of the protests and our placebo tests rule out the possibility that our findings are attributable to chance. Our research informs policy makers and provides insights regarding the usefulness of social distancing as an intervention to minimize the spread of SARS-CoV-2.

The role of L-type amino acid transporter 1 (Slc7a5) during in vitro myogenesis.

Satellite cells are required for muscle regeneration, remodeling, and repair through their activation, proliferation, and differentiation; however, how dietary factors regulate this process remains poorly understood. The L-type amino acid transporter 1 (LAT1) transports amino acids, such as leucine, into mature myofibers, which then stimulate protein synthesis and anabolic signaling. However, whether LAT1 is expressed on myoblasts and is involved in regulating myogenesis is unknown. The aim of this study was to characterize the expressional and functional relevance of LAT1 during different stages of myogenesis and in response to growth and atrophic conditions in vitro. We determined that LAT1 is expressed by C2C12 and human primary myoblasts, and its gene expression is lower during differentiation (P < 0.05). Pharmacological inhibition and genetic knockdown of LAT1 impaired myoblast viability, differentiation, and fusion (all P < 0.05). LAT1 protein content in C2C12 myoblasts was not significantly altered in response to different leucine concentrations in cell culture media or in two in vitro atrophy models. However, LAT1 content was decreased in myotubes under atrophic conditions in vitro (P < 0.05). These findings indicate that LAT1 is stable throughout myogenesis and in response to several in vitro conditions that induce muscle remodeling. Further, amino acid transport through LAT1 is required for normal myogenesis in vitro.

Exercise Improves Cancer-free Survival and Health Span in a Model of Radiation-induced Cancer.

INTRODUCTION: Radiation therapy increases the risk of secondary malignancy and morbidity in cancer survivors. The role of obesity and exercise training in modulating this risk is not well understood. As such, we used a preclinical model of radiation-induced malignancy to investigate whether diet-induced obesity and/or endurance exercise training altered lifelong survival, cancer incidence, and morbidity. METHODS: Male CBA mice were randomly divided into control diet/sedentary group (CTRL/SED), high-fat diet (45% fat)/sedentary group (HFD/SED), control diet/exercise group (2-3 d·wk-1; CTRL/EX), or high-fat diet/exercise group (HFD/EX) groups then exposed to whole-body radiation (3 Gy). End point monitoring and pathology determined mortality and cancer incidence, respectively. Health span index, a measure of morbidity, was determined by a composite measure of 10 anthropometric, metabolic, performance, and behavioral measures. RESULTS: Overall survival was higher in HFD/SED compared with CTRL/SED (P < 0.05). The risk of cancer-related mortality by 18 months postradiation was 1.99 and 1.63 in HFD/SED compared with CTRL/EX (RR = 1.99, 95% confidence interval = 1.20-3.31, P = 0.0081) and CTRL/SED (RR = 1.63, 95% confidence interval = 1.06-2.49, P = 0.0250), respectively. The number of mice at end point with cancer was higher in HFD/SED compared with CTRL/EX and CTRL/SED (P < 0.05). Health span index was highest in CTRL/EX (score = +2.5), followed by HFD/EX (score = +1), and HFD/SED (score = -1) relative to CTRL/SED. CONCLUSION: This work provides the basis for future preclinical studies investigating the dose-response relationship between exercise training and late effects of radiation therapy as well as the mechanisms responsible for these effects.

Weight loss with exercise improves muscle architecture and progenitor cell populations compared with weight loss alone in mice with preneoplastic colorectal lesions.

Weight loss and exercise reduce colorectal cancer (CRC) risk in persons with obesity. Whether weight loss and exercise effect myofiber characteristics and muscle stem/progenitor cell populations in mice with preneoplastic colorectal lesions, a model of CRC risk, is unknown. To address this gap, male C57Bl/6J mice were fed a high-fat diet (HFD) to induce obesity or a control (CON) diet prior to azoxymethane injection to induce preneoplastic colorectal lesions. The HFD group was then randomized to weight loss conditions that included (1) switching to the CON diet only (HFD-SED) or switching to the CON diet with treadmill exercise training (HFD-EX). Average myofiber cross-sectional area was not different between groups. There were more smaller-sized fibres in HFD-EX (p < 0.05 vs. CON), and more fibrosis in HFD-SED (p < 0.05 vs. HFD-EX and CON). There was a trend for more committed (Pax7+MyoD+) myoblasts (p = 0.059) and more fibro-adipogenic progenitors in HFD-EX (p < 0.05 vs. CON). Additionally, the canonical pro-inflammatory marker p-NF-κB was markedly reduced in the interstitium of HFD-EX (p < 0.05 vs. CON and HFD-SED). Our findings suggest that in mice with preneoplastic colorectal lesions, HFD followed by weight loss with exercise reduces muscle fibrosis and results in a higher content of muscle stem/progenitor cells. Novelty: Exercise improves muscle architecture in mice with preneoplastic colorectal lesion Exercise increases fibro/adipogenic progenitors and reduces inflammatory signaling in mice with preneoplastic colorectal lesions.

Degradable Hydrogels for the Delivery of Immune-modulatory Proteins in the Wound Environment.

Chronic wounds represent a growing clinical problem for which limited treatment strategies exist. Defects in immune cell-mediated healing play an important role in chronic wound development, presenting an attractive clinical target in the treatment of chronic wounds. However, efforts to improve healing through the application of growth factors and cytokines have been limited by the rapid degradation and diffusion of these molecules in the wound environment. In this study we sought to overcome the challenge of rapid diffusion through the development of a hydrogel delivery system in which protein cargo can be released into the wound environment at a constant and tunable rate. This system was used to deliver the intercellular adhesion molecule-1 (ICAM-1) in order to target endogenous cells upstream of growth factor and cytokine production and circumvent the issue of their rapid degradation. We demonstrated that our delivery system was able to release cargo at different and highly controllable rates and thereby improved cargo retention in the wound environment. Additionally, treatment with ICAM-1 in the delivery system improved healing in both ICAM-1-deficient mice and an aged mouse model of delayed healing, highlighting a potential clinical benefit for this protein in the treatment of chronic wounds.

Lower extremity characteristics in recurrent clubfoot: Clinical and gait analysis findings that may influence decisions for additional surgery.

BACKGROUND: Patients with recurrent clubfoot may seek intervention to address impairments that impact gait function. An understanding of these impairments and associated gait issues will provide valuable information about ongoing treatment requirements. RESEARCH QUESTION: The purpose of this study was to describe the prevalence of impairments and associated gait deviations in children with recurrent clubfoot and to evaluate whether these findings differ depending on unilateral or bilateral presentation. METHODS: Eighty-four affected feet (42 unilateral, 21 bilateral) were retrospectively reviewed. History, clinical exam, and gait data were collected. Statistical analysis included evaluations of associations between clinical exam and gait parameters and differences among patients with unilateral versus bilateral clubfoot and a database of healthy controls. RESULTS: The average age was 7.5 ±â€¯3.3 years for unilateral and 7.0 ±â€¯2.8 years for bilateral patients. Patients presented with limited passive ankle dorsiflexion (unilateral/bilateral:67%/57%), limited ankle plantar flexion strength (unilateral/bilateral:53%/55%), metatarsus adductus (unilateral/bilateral:86%/83%) and internal foot-thigh angles (unilateral/bilateral:83%/82%), while only a subset presented with internal bi-malleolar axis angles (unilateral/bilateral:36%/45%). The most common gait deviations were internal foot progression (unilateral/bilateral:76%/73%), external hip rotation (unilateral/bilateral:66%/69%), reduced peak ankle plantar flexion moments (unilateral/bilateral:84%/83%), and reduced peak ankle power generation (unilateral/bilateral:67%/74%). Passive dorsiflexion was significantly correlated with peak dorsiflexion during stance and swing in both groups. Patients with unilateral compared to bilateral clubfoot showed decreased peak dorsiflexion and an associated knee flexor moment. SIGNIFICANCE: Patients with recurrent clubfoot show gait deviations at the ankle that can be explained by joint level impairment and compensations at the knee, hip and pelvis. Patients with unilateral clubfoot typically show decreased dorsiflexion range of motion and associated greater gait impacts and compensations than bilateral clubfoot. Understanding the relationships between impairments and gait function and the implications of unilateral versus bilateral clubfoot will help improve prognostic ability and optimize future treatment outcomes.

Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT.

BACKGROUND: Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI. OBJECTIVE: To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds. DESIGN: Phase A - semistructured interviews, outcome measure development, practice survey, literature reviews and value-of-information analysis. Phase B - pilot RCT with qualitative research and questionnaire validation. Patients and the public were involved. SETTING: Usual NHS care. PARTICIPANTS: Patients undergoing elective/non-elective abdominal surgery, including caesarean section. INTERVENTIONS: Phase A - none. Phase B - simple dressing, glue-as-a-dressing (tissue adhesive) or 'no dressing'. MAIN OUTCOME MEASURES: Phase A - pilot RCT design; SSI, patient experience and wound management questionnaires; dressing practices; and value-of-information of a RCT. Phase B - participants screened, proportions consented/randomised; acceptability of interventions; adherence; retention; validity and reliability of SSI measure; and cost drivers. DATA SOURCES: Phase A - interviews with patients and health-care professionals (HCPs), narrative data from published RCTs and data about dressing practices. Phase B - participants and HCPs in five hospitals. RESULTS: Phase A - we interviewed 102 participants. HCPs interpreted 'dressing' variably and reported using available products. HCPs suggested practical/clinical reasons for dressing use, acknowledged the weak evidence base and felt that a RCT including a 'no dressing' group was acceptable. A survey showed that 68% of 1769 wounds (727 participants) had simple dressings and 27% had glue-as-a-dressing. Dressings were used similarly in elective and non-elective surgery. The SSI questionnaire was developed from a content analysis of existing SSI tools and interviews, yielding 19 domains and 16 items. A main RCT would be valuable to the NHS at a willingness to pay of £20,000 per quality-adjusted life-year. Phase B - from 4 March 2016 to 30 November 2016, we approached 862 patients for the pilot RCT; 81.1% were eligible, 59.4% consented and 394 were randomised (simple, n = 133; glue, n = 129; no dressing, n = 132); non-adherence was 3 out of 133, 8 out of 129 and 20 out of 132, respectively. SSI occurred in 51 out of 281 participants. We interviewed 55 participants. All dressing strategies were acceptable to stakeholders, with no indication that adherence was problematic. Adherence aids and patients' understanding of their allocated dressing appeared to be key. The SSI questionnaire response rate overall was 67.2%. Items in the SSI questionnaire fitted a single scale, which had good reliability (test-retest and Cronbach's alpha of > 0.7) and diagnostic accuracy (c-statistic = 0.906). The key cost drivers were hospital appointments, dressings and redressings, use of new medicines and primary care appointments. LIMITATIONS: Multiple activities, often in parallel, were challenging to co-ordinate. An amendment took 4 months, restricting recruitment to the pilot RCT. Only 67% of participants completed the SSI questionnaire. We could not implement photography in theatres. CONCLUSIONS: A main RCT of dressing strategies is feasible and would be valuable to the NHS. The SSI questionnaire is sufficiently accurate to be used as the primary outcome. A main trial with three groups (as in the pilot) would be valuable to the NHS, using a primary outcome of SSI at discharge and patient-reported SSI symptoms at 4-8 weeks. TRIAL REGISTRATION: Phase A - Current Controlled Trials ISRCTN06792113; Phase B - Current Controlled Trials ISRCTN49328913. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 39. See the NIHR Journals Library website for further project information. Funding was also provided by the Medical Research Council ConDuCT-II Hub (reference number MR/K025643/1).

Wound infections are common after surgery. Some are cured with simple treatment, but others may lead to serious problems. Reducing the risk of a wound infection is important. We do not know if the type of dressing, or not using a dressing, influences the risk of infection. A study that allocated patients to receive different dressings (or no dressing) would answer this question. We did preliminary research to explore whether or not such a study is possible. We interviewed doctors, nurses and patients about their views on dressings and a future study. We also described dressings currently being used in the NHS and found that simple dressings and tissue adhesive (glue) 'as-a-dressing' are used most frequently. We studied existing evidence and interviewed experts to develop a questionnaire, completed by patients, to identify wound infections after patients leave hospital and tested its accuracy. We also explored taking photographs of wounds. We investigated whether or not a major study would be worth the cost and designed a pilot study to test its feasibility. The pilot study recruited 394 patients undergoing abdominal operations in five NHS hospitals. These patients were allocated to have a simple dressing, glue-as-a-dressing or no dressing, and 92% received the allocated dressing method. Patients and their doctors and nurses found the dressing methods to be acceptable. We showed that the new patient questionnaire accurately identified infections. Patients or their carers also found it acceptable to photograph their wounds. Our research suggests that a future large study would be worth the investment and is possible.

Transvaginal Cystolithotomy: A Novel Approach.

OBJECTIVE: To describe a novel surgical option for cystolithiasis management in female patients with no urethral access and prior abdominal surgeries. We present a 51-year-old female with a history of traumatic spinal cord injury with pelvic fractures and resultant neurogenic bladder. She underwent transabdominal bladder neck closure and bladder augmentation with continent diversion 2 years prior. CT abdomen/pelvis demonstrated a 3 cm stone and significant amount of bowel anterior to the bladder. METHODS: Pouchoscopy was performed via ureteroscope through the catheterizable stoma to assess stone location and mobility. A 14F-Foley was inserted for intraoperative decompression. An inverted-U incision was made on the anterior vaginal wall overlying the bladder base. Sharp and blunt dissection was performed in an avascular plane to dissect the vagina off of the bladder. Electrocautery was utilized to open perivesical tissue and the detrusor layer transversely. Further sharp dissection of perivesical tissue was achieved using Metzenbaum scissors. The bladder was filled via stoma Foley to improve visualization of bladder mucosa. Cystotomy was made and the 3 cm stone was removed, intact, using a Babcock. The bladder was closed in 2 layers with absorbable suture in running fashion. The bladder was refilled and the closure was watertight. The outer detrusor layer was closed with running locking 2-0 Polysorb, and a separate layer of perivesical tissue was closed over our 2-layer bladder closure using simple interrupted stitches. The vaginal flap was closed with running-locking 2-0 Polysorb. RESULTS: Operative time was 55 minutes. Estimated blood loss was 25 cc. The patient was discharged on postoperative-day 0 with a 14F-Foley in the catheterizable channel. The Foley was removed at the 3-week postoperative visit and patient resumed self-catheterization. No postoperative imaging was required. No complications were reported within 1 year. CONCLUSION: We demonstrate the feasibility of transvaginal cystolithotomy in females with bowel overlying bladder and no urethral access.

The Late Effects of Radiation Therapy on Skeletal Muscle Morphology and Progenitor Cell Content are Influenced by Diet-Induced Obesity and Exercise Training in Male Mice.

Radiation exposure during muscle development induces long-term decrements to skeletal muscle health, which contribute to reduced quality of life in childhood cancer survivors. Whether the effects of radiation on skeletal muscle are influenced by relevant physiological factors, such as obesity and exercise training remains unknown. Using skeletal muscle from our previously published work examining the effects of obesity and exercise training on radiation-exposed bone marrow, we evaluated the influence of these physiological host factors on irradiated skeletal muscle morphology and cellular dynamics. Mice were divided into control and high fat diet groups with or without exercise training. All mice were then exposed to radiation and continued in their intervention group for an additional 4 weeks. Diet-induced obesity resulted in increased muscle fibrosis, while obesity and exercise training both increased muscle adiposity. Exercise training enhanced myofibre cross-sectional area and the number of satellite cells committed to the myogenic lineage. High fat groups demonstrated an increase in p-NFĸB expression, a trend for a decline in IL-6, and increase in TGFB1. These findings suggest exercise training improves muscle morphology and satellite cell dynamics compared to diet-induced obesity in irradiated muscle, and have implications for exercise interventions in cancer survivors.

Education Research: Evaluation of curriculum to teach resilience skills to neurology residents.

OBJECTIVE: To evaluate feasibility and acceptability of a health professional resilience skills training program with neurology residents. METHODS: The curriculum consists of five 1-hour-long modules that included the following skills: reflective narrative practices, emotion regulation, communication with highly distressed individuals, boundary management, and the identification of depression and trauma. Using a web-based survey tool, we administered the Brief Resilience Scale (BRS) and Abbreviated Maslach Burnout Inventory (aMBI) at baseline, in addition to a pre- and post-survey assessing change in beliefs and self-efficacy, as well as satisfaction with the intervention. Means were compared using the Wilcoxon rank-sum and signed rank tests. RESULTS: Twenty-two residents representing each year of training completed the pre-survey; 41% were women. Subscale scores on the aMBI revealed that 50% had moderate or high emotional exhaustion, 41% had moderate depersonalization, and 37% had moderate or low personal accomplishment, though 77.3% reported high career satisfaction. Female residents had lower scores on the BRS (mean 3.26 vs 3.88, p < 0.05), though scores on aMBI subscales did not differ by sex. Scores did not differ by year of training. Sixteen residents completed both the pre- and post-survey. Significant increases were detected in 4 of 9 self-efficacy statements. Seventy-one percent of residents were satisfied or extremely satisfied with the training. CONCLUSIONS: Residents were satisfied with the curriculum and reported improved ability to identify and cope with work-related stress. Further study is needed to evaluate the influence of skills adoption and practice on resilience and burnout.

Feasibility of same day discharge after robotic assisted pelvic floor reconstruction.

INTRODUCTION: Robotic surgical procedures have become more common in female pelvic reconstruction. Purported benefits of robotic assisted pelvic floor reconstruction (RAPFR) procedures include shorter hospital stay, faster recovery, lower blood loss, and decreased postoperative pain. Following RAPFR procedures, the current accepted practice is discharge after a one-night hospitalization. We assessed whether same day discharge (SDD) affects the short term safety of and patient satisfaction with robotic assisted pelvic floor reconstructive procedures, relative to those who remain hospitalized overnight. MATERIALS AND METHODS: We retrospectively reviewed the charts of women who underwent RAPFR procedures between October 2015 and October 2016. A same day discharge protocol for RAPFR was initiated in July 2016. To date, 10 patients have undergone SDD. These patients were compared to the consecutive patients from the prior 9 months who stayed overnight. To evaluate short term safety, we reviewed the medical record for any unscheduled Cleveland Clinic emergency department (ED) and/or office visits within 30 days of the RAPFR procedure. We then sent a mailed survey to all patients, querying their pelvic organ prolapse-related PGI-I and also offering a postoperative satisfaction questionnaire. Demographic, perioperative, postoperative data and survey results were compared using Student's t test and Fisher's exact test. RESULTS: In our series, 38 patients (95%) underwent robotic assisted sacrocolpopexy (RASC). Only 2 (5%) had a different RAPFR procedure, a robotic assisted vaginal mesh excision. Concomitant robotic assisted supracervical hysterectomy (SCH) was performed in 9 patients (30%) in the overnight group, whereas 1 of the SDD patients underwent SCH (10%). Demographics and operative characteristics did not differ between groups. Ultimately, patients in the SDD group were no more likely than the overnight group to require an unscheduled ED or office visit in the early postoperative period. With respect to satisfaction, no significant differences were observed between groups, with both groups noting substantial improvement in POP symptoms following surgery. CONCLUSIONS: In this pilot study, same day discharge after RAPFR procedures appears to be safe and feasible. RAPFR procedures were well-tolerated, with no difference in ED or non-urology office visits occurring during the early post-operative period in our series, regardless of length of stay. Patient satisfaction was equivalent between groups and universally high.

International Continence Society best practice statement for use of sacral neuromodulation.

AIMS: Sacral neuromodulation (SNM) is an accepted therapy for a variety of conditions. However, despite over 20 years of experience, it remains a specialized procedure with a number of subtleties. Here we present the recommendations issued from the International Continence Society (ICS) SNM Consensus Panel. METHODS: Under the auspices of the ICS, eight urologists, three colorectal surgeons and two urogynecologists, covering a wide breadth of geographic and specialty interest representation, met in January 2017 to discuss best practices for neuromodulation. Suggestions for statements were submitted in advance and specific topics were assigned to committee members, who prepared and presented supporting data to the group, at which time each topic was discussed in depth. Best practice statements were formulated based on available data. This document was then circulated to multiple external reviewers after which final edits were made and approved by the group. RESULTS: The present recommendations, based on the most relevant data available in the literature, as well as expert opinion, address a variety of specific and at times problematic issues associated with SNM. These include the use of SNM for a variety of underlying conditions, need for pre-procedural testing, use of staged versus single-stage procedures, screening for success during the trial phase, ideal anesthesia, device implantation, post-procedural management, trouble-shooting loss of device function, and future directions for research. CONCLUSIONS: These guidelines undoubtedly constitute a reference document, which will help urologists, gynecologists, and colorectal surgeons optimize their use of SNM for refractory urinary urgency and frequency, UUI, NOR, and FI.

Improving the utility of clinical phenotyping in interstitial cystitis/painful bladder syndrome: from UPOINT to INPUT.

INTRODUCTION: The phenotyping system UPOINT has proven effective in classifying patients with Urologic Pelvic Pain Syndromes in a clinically meaningful way and to guide therapy. While highly successful in men with chronic pelvic pain syndrome (CPPS), UPOINT is more limited in patients with interstitial cystitis/painful bladder syndrome (IC/PBS) since by definition all patients have the urinary and organ specific phenotype. Furthermore, AUA guidelines recommend a sequential tiered approach to therapy rather than the multimodal UPOINT scheme. We sought to modify UPOINT to be more practical and efficacious for IC/PBS. MATERIALS AND METHODS: We developed a new phenotype by removing the urinary and organ specific domains from UPOINT and adding a Hunner's ulcers (U) domain, since these patients benefit from phenotype specific therapies (fulguration, cyclosporine). This yields 'INPUT': infection, neurologic/systemic, psychosocial, ulcers and tenderness of muscles. We applied this system retrospectively to our previously validated upointmd.com IC/PBS database. Symptoms were measured by the Genitourinary Pain Index (GUPI) (valid for men and women). The database was searched for patients with complete data to assess the INPUT domains and include GUPI. Men were included if they reported pain relieved by voiding and/or presence of Hunner's ulcers. Groups were compared with ANOVA, Mann-Whitney, t test or chi squared when appropriate and correlated with Spearman r. RESULTS: There were 239 patients, 154 female (64%) with age range 18-79 (mean 41.8). Incidence of domains was infection 11%, neurologic/systemic 51%, psychosocial 81%, ulcers 18% and tenderness 85%. Mean total domains was 2.46 (range 0-5) and 65% had 2 or 3 positive domains while only 5% had none. There was a stepwise increase in GUPI score with increasing number of positive INPUT domains (ANOVA for differences between groups p < 0.0001. Correlation by Spearman r = 0.355 p < 0.0001). Presence of Hunner's ulcers increased mean symptom score (25.7 versus 29.7, p = 0.004) and indeed each of the domains significantly increased total GUPI score except for Infection. CONCLUSIONS: The INPUT phenotype in IC/PBS appears to replicate the validity and potential clinical utility of UPOINT in CPPS. Patients have a diversity of phenotypes and more positive domains correlate with more severe symptoms. Since 95% of patients have at least 1 positive domain it may benefit patients to receive multimodal therapy up front for these extra domains (eg. pelvic floor physical therapy, fulguration of ulcers) rather than relying on a sequential tiered approach.

Mechanism of Action of the Transobturator Sling for Post-Radical Prostatectomy Incontinence: A Multi-institutional Prospective Study Using Dynamic Magnetic Resonance Imaging.

OBJECTIVE: To compare the length of the membranous (functional) urethra in male patients who underwent the male transobturator sling (TOS) for postradical prostatectomy urinary incontinence (PPI). The TOS is in established use for treatment of PPI; however, the precise mechanism of action is unknown. MATERIALS AND METHODS: This is a prospective case-controlled study on men undergoing male TOS surgery from 2008 to 2014. The comparison arm included patients without incontinence after radical prostatectomy. All participants underwent dynamic magnetic resonance imaging (MRI) at baseline and this was repeated after TOS placement for those who underwent the procedure. Three standardized points were measured using MRI and compared in both groups in addition to clinical measures. RESULTS: Thirty-nine patients were enrolled and 31 patients completed the protocols. The controls (N = 14) had a longer vesicourethral anastomosis to urethra measured at the penile bulb (functional urethral length) distance compared to the pre-TOS group at rest (1.92 cm controls vs 1.27 cm pre-TOS, P = .0018) and at Valsalva (2.13 cm controls vs 1.72 cm pre-TOS, P = .0371). Placement of the sling (N = 17) increased the functional urethral length distance at rest (1.92 cm control vs 1.53 cm post-TOS, P = .09) and at Valsalva (1.94 cm post-TOS vs 2.13 cm control, P = .61), so that the difference was no longer statistically significant. CONCLUSION: We identified that one possible mechanism in improvement in stress urinary incontinence post-TOS placement is the lengthening of the vesicourethral anastomosis to bulbar-urethra distance. This is the first such study utilizing dynamics MRI in post prostatectomy controls, incontinent pre-TOS, and post-TOS to assess and show these findings.

Trends in urodynamic testing prior to midurethral sling placement-What was the value of the VALUE trial?

BACKGROUND: Many urologists use urodynamic testing (UDS) to assist clinical decision-making. The VALUE study, a multi-institutional, randomized controlled trial published in 2012, demonstrated that UDS prior to midurethral sling placement for uncomplicated stress urinary incontinence (SUI) did not change management. We sought to determine whether use of UDS for evaluation of SUI diminished thereafter. METHODS: Records of patients who underwent isolated mid-urethral sling surgery at our tertiary-care referral center from 2008 to 2009 (pre-VALUE) and 2014 to 2016 (post-VALUE) were reviewed. Comorbidities, presenting symptoms, surgeon specialty, use of UDS, UDS results and sling type were recorded. Patients with neurologic comorbidities or prior anti-incontinence procedures were excluded. Descriptive statistics were calculated and multivariable logistic regression analyses performed. RESULTS: Three hundred and eighty-seven patients met inclusion criteria. Median age was 54 years. Patients most frequently presented with stress urinary incontinence (56% pre, 50% post), followed by stress predominant mixed urinary incontinence (40% pre, 48% post, P = 0.09). Before VALUE, UDS was performed in 70% of patients prior to primary sling; in the later cohort, this decreased to 41% (P < 0.0001). On multivariable analysis, provider specialty (P < 0.0001) and belonging to the pre-VALUE cohort (P = < 0.0001) predicted use of UDS prior to sling. CONCLUSION: It is paramount that new data be incorporated into diagnostic and treatment algorithms. We found that the rate of preoperative urodynamic testing decreased after publication of a randomized-controlled trial demonstrating that these studies did not change procedural decision-making. Future studies that identify instances of over-testing may have the ability to positively impact patient care and contain costs.