Expert Consensus on Pediatric Urodynamics Reporting Using Modified Delphi Technique.

PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.

Intradetrusor botox injection and augmentation cystoplasty trends among spina bifida patients at US freestanding children's hospitals.

INTRODUCTION: Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida. Furthermore, there are little data regarding its use relative to bladder augmentation and patient volume on a national scale. OBJECTIVE: We sought to investigate the contemporary trends of intra-detrusor Botox injection and augment cystoplasty in free-standing children's hospitals. STUDY DESIGN: We queried the Pediatric Health Information System database to identify spina bifida patients from 2016 to 2019 who underwent intra-detrusor Botox injection and augment cystoplasty based on CPT and ICD-10 codes. Total spina bifida population under care in the free-standing children's hospitals was estimated by all inpatient and ambulatory surgery encounters as denominators to calculate frequency by time for both intra-detrusor Botox injections and augmentation cystoplasty. RESULTS: In total, we included 1924 intra-detrusor Botox injections and 842 augmentation cystoplasties. 1413 (51.1%) patients were female. Median age at surgery was 10.0 (interquartile range 6.98-13.5) years. There was a significant increase in intra-detrusor Botox injection frequency (p < 0.001). While there was an overall decreasing, but not significant, trend for augmentation cystoplasty, there was a significant increase in this procedure during the summer months compared to the rest of the year (p < 0.001, Figure 1). Sensitivity analysis using only first intra-detrusor Botox injection per patient demonstrated similarly significant increasing trend. DISCUSSION: Use of intra-detrusor Botox injection for the management of neurogenic bladder has significantly increased among patients with spina bifida while augmentation cystoplasty has slightly decreased, but not significantly. CONCLUSIONS: Over time, practice patterns for the treatments of neurogenic bladder among spina bifida children have favored minimally invasive Botox injections while augmentation cystoplasty use has not significantly changed.

The impact of clean intermittent catheterization on students and families in the school environment.

INTRODUCTION: Clean intermittent catheterization (CIC) is often used for bladder emptying in children with lower urinary tract dysfunction. Until recently, the emphasis in assessing the effects of CIC has been on preserving kidney function, reducing urinary tract infection, and achieving urinary continence. Few studies have investigated the impact of CIC on students and families in a school setting. This study sought to examine what students and caregivers experienced when CIC was required during the school day and how schools adjusted to a student needing to perform it. MATERIALS AND METHODS: A phenomenological approach utilizing semistructured interviews was performed to understand the impact of CIC on students. Purposeful sampling identified eligible families. A guide was developed from expert opinion validated by a pilot sample with feedback collated into a family/provider codesigned questionnaire. Interviews emphasized the impact and challenges students faced at school. Transcripts were coded using Dedoose software with emerging themes identified and a code book was created for closed coding that led to thematic analysis. RESULTS: A total of 40 families (52 caregivers and children > 12 years) were interviewed. Emergent themes included: Caregivers and students felt (1) school personnel were not always aware of nor prepared regarding the implications of CIC; (2) school bathrooms were often less than ideal (e.g., location, size, cleanliness, privacy, and availability); and (3) student participation in extracurricular activities was challenging. CONCLUSIONS: This study identifies potential areas of intervention in meeting the needs of students who require CIC and the importance of having collaborative efforts of caregivers, health care providers, and school personnel in addressing and meeting CIC needs. Care coordination that involves consistent communication and careful planning between health care teams, school personnel, students, and caregivers can optimize a student's educational experience.

Facilitators and challenges to transitioning to self-catheterization: Patient and caregiver perspectives.

INTRODUCTION: Clean intermittent catheterization (CIC) is a well-established method of managing lower urinary tract dysfunction. Depending on the age at introduction, caregivers might perform CIC initially but then transition responsibility to their children. Little is known about how to support families during this transition. Our aim is to learn the facilitators and challenges experienced when supporting the transition from caregiver-led CIC to patient self-CIC. MATERIALS AND METHODS: A phenomenological approach was used to gather information from caregivers and children >12 years through semistructured interviews. Thematic analysis was utilized to generate themes around experience with the transition from caregiver-led CIC to patient self-CIC. RESULTS: Of the 40 families interviewed, 25 families underwent successful transition to patient self-CIC. Analysis of excerpts identified a three-step process, including (1) desiring to learn self-CIC, (2) practical learning of CIC techniques, and (3) mastering of techniques leading to emotional and physical independence. Many families experienced challenges in transitioning to self-CIC, including patient or caregiver reluctance, improper equipment, past negative experiences, lack of knowledge about urinary tract anatomy and function, abnormal anatomy, and/or moderate to severe intellectual disability. DISCUSSION: Authors reviewed interventions to address challenges and provide clinical care recommendations to enhance success during the transition to patient self-CIC. CONCLUSION: No prior studies have identified this stepwise process that occurs in the transition from caregiver-led CIC to patient self-CIC. Healthcare providers and school officials (where indicated) can support families during this transition, with attention to facilitators and challenges identified in this study.

Improvement of Islet Engrafts via Treg Induction Using Immunomodulating Polymeric Tolerogenic Microparticles.

Type 1 diabetes (T1D) is a life-threatening condition for which islet transplantation offers a way to extend longevity and vastly improve quality of life, but the degree and duration of success can vary greatly due to the patient's protective immunity against foreign material. The field is in need of cellular engineering modalities to promote a localized, tolerogenic environment to protect transplanted islet tissue. Artificial antigen-presenting cells (aAPCs) can be designed exogenously to mimic immune cells, such as dendritic cells, and administered to patients, allowing greater control over T cell differentiation. As regulatory T cell (Treg) modulation can reduce the activity of cytotoxic T-effector populations, this strategy can be used to promote immune acceptance of both biomaterials and cellular transplants, such as islets. A new class of poly(lactic-co-glycolic acid) (PLGA) and PLGA/PBAE-blend aAPCs containing transforming growth factor beta and conjugated with anti-CD3 and anti-CD28 antibodies, called tolerogenic aAPCs (TolAPCs), are specifically designed to generate a tolerogenic response by inducing Tregs. We characterized TolAPCs' physical and chemical properties via advanced particle imaging and sizing modalities and investigated their impact on the local and systemic immune system across BALB/c and C57BL/6 mouse strains as well as healthy male and female mice via histologic, gene expression, and immunofluorescence staining methods. Strain-specific differences were observed, whereas sex made no difference in the TolAPC response. TolAPCs stimulated the expansion of FOXP3+ Tregs and provided islet cell protection, maintaining improved glucose-stimulated insulin secretion in vitro when co-cultured with cytotoxic CD8+ T cells. We also explored the ability of this TolAPC platform to promote tolerance in a streptozotocin-induced murine T1D C57BL/6 mouse model. We achieved partial islet protection over the first few days following co-injection with PLGA/PBAE TolAPCs; however, grafts failed soon thereafter. Analysis of the local injection site demonstrated that other immune cell types, including APCs and cytotoxic natural killer cells, increased in the islet injection site. While we aimed to promote a localized tolerogenic microenvironment in vivo using biodegradable TolAPCs to induce Tregs and extend islet transplant durability, further TolAPC improvements will be required to both elongate efficacy and control additional immune cell responders.

Low-Intensity Pulsed Ultrasound Neuromodulation of a Rodent's Spinal Cord Suppresses Motor Evoked Potentials.

OBJECTIVE: Here we investigate the ability of low-intensity ultrasound (LIUS) applied to the spinal cord to modulate the transmission of motor signals. METHODS: Male adult Sprague-Dawley rats (n = 10, 250-300 g, 15 weeks old) were used in this study. Anesthesia was initially induced with 2% isoflurane carried by oxygen at 4 L/min via a nose cone. Cranial, upper extremity, and lower extremity electrodes were placed. A thoracic laminectomy was performed to expose the spinal cord at the T11 and T12 vertebral levels. A LIUS transducer was coupled to the exposed spinal cord, and motor evoked potentials (MEPs) were acquired each minute for either 5- or 10-minutes of sonication. Following the sonication period, the ultrasound was turned off and post-sonication MEPs were acquired for an additional 5 minutes. RESULTS: Hindlimb MEP amplitude significantly decreased during sonication in both the 5- (p < 0.001) and 10-min (p = 0.004) cohorts with a corresponding gradual recovery to baseline. Forelimb MEP amplitude did not demonstrate any statistically significant changes during sonication in either the 5- (p = 0.46) or 10-min (p = 0.80) trials. CONCLUSION: LIUS applied to the spinal cord suppresses MEP signals caudal to the site of sonication, with recovery of MEPs to baseline after sonication. SIGNIFICANCE: LIUS can suppress motor signals in the spinal cord and may be useful in treating movement disorders driven by excessive excitation of spinal neurons.

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier-White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey-Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population-based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.

The art of introducing clean intermittent catheterization: How families respond and adapt: A qualitative study.

INTRODUCTION: Since its inception >50 years ago, clean intermittent catheterization (CIC) has become ubiquitous in managing lower urinary tract dysfunction in children. Emphasis has been on its impact on daily life, but little on its implementation and adjustment in families. The aim of the current study was to discover how families learned to implement and manage their child's CIC needs by interviewing caregivers, adolescents, and young adults about their experiences. Interviews were designed to uncover facilitators and barriers to beginning CIC to initiate potential improvements in a multidisciplinary approach. METHODS: A semi-structured interview guide was developed and piloted initially to 12 families for validation. Between August 2018 and October 2019, 40 families (52 interviews of caregivers and patients >12 years) were then interviewed with open-ended questions interspersed with more specific ones to generate discussion. Transcripts were coded using Dedoose software to create a base list with emergent codes. Inductive and deductive methods were employed to generate themes. Consensus was reached during successive team meetings. RESULTS: Five major and several subthemes emerged regarding implementation of CIC by caregivers and patients learning CIC for the first time. THEME 1: Parental reaction to CIC: Caregivers described benefits of an adjustment period on learning their child's need for CIC. Prenatal information to caregivers of spina bifida children gave them time to mentally process the need for CIC. THEME 2: Ease of learning CIC: impact of age and gender: caregivers identified advantages of initiating CIC in infancy. Caregivers speculated CIC was physically easier in boys than girls due to meatus location. Developmentally ready children expressed a desire for independence and privacy as they learned to initiate CIC. THEME 3: The impact of additional caregiver support in learning and performing CIC: presence of multiple caregivers optimized learning and implementation of CIC. Having secondary caregivers available provided peace of mind and more flexibility in maintaining reliable CIC care. Patients learning CIC found it helpful to have a parent present at the teaching session. Occasionally, female caregivers reported feelings of anger and frustration when male caregivers were reluctant to be involved in catheterization, irrespective of their child's gender. THEME 4: Satisfaction with healthcare team's approach: The healthcare team's responsiveness to their learning needs affected how they mastered CIC. The healthcare team's teaching and reassurance helped build caregiver confidence. Developmentally appropriate children were able to learn self-catheterization when supported by the healthcare team. Patients learning self-CIC articulated having a supportive healthcare team was helpful with implementation. THEME 5: Effect of CIC on employment status relative to job changes, insurance, and daycare: implementing and performing CIC presented a spectrum of issues related to employment. Educating employers regarding CIC facilitated a caregiver's ability to both remain at work and administer to their child. Caregivers underscored the importance of adequate insurance when considering employment choices. Concerns about daycare availability affected caregivers' work schedules. CONCLUSIONS: It is anticipated this information will aid healthcare personnel to more effectively teach and initiate CIC in families, and in individuals learning for the first time. The findings should serve as the basis for conducting future patient satisfaction studies, which would determine the effectiveness and reproducibility of these approaches.

Accuracy of contrast-enhanced voiding urosonography using Optison™ for diagnosis of vesicoureteral reflux in children.

BACKGROUND: There is limited quality of evidence regarding the accuracy of contrast-enhanced voiding urosonography (ceVUS) for diagnosis of vesicoureteral reflux (VUR) compared to fluoroscopic voiding cystourethrography (VCUG), and minimal data on the use of the ultrasound contrast agent Optison™ for this purpose. OBJECTIVE: To compare the accuracy of ceVUS using Optison™ to VCUG, and to assess inter-rater agreement regarding presence and grading of VUR. STUDY DESIGN: In this retrospective investigation, all sequential ceVUS with Optison™ and VCUG studies performed in children between 2014 and 2017 were reviewed. Two raters independently graded all ceVUS studies using a 5-point scale. CeVUS sensitivity and specificity were estimated separately for each rater using the VCUG report as the ground truth for presence and degree of VUR. Logistic and ordinary linear regression models assessed rater-report agreement and inter-rater agreement for each kidney, Optison™ dose, and referral diagnosis. RESULTS: 97 children (51 females) with 101 paired studies were included. Sensitivity and specificity of ceVUS for VUR detection were identical for both raters: right kidney 75%/90.9%; left kidney 85.7%/78.9% (Figure). There was no statistically significant difference in disagreement between raters and the VCUG report for the right or left kidney. Inter-rater agreement on ceVUS grading was 90% and 88% for right and left kidneys, respectively. There was a significant negative association between fetal hydronephrosis vs urinary tract infection and disagreement between Rater 2 and the VCUG report for the left kidney. There were no other significant associations with respect to either kidney, Optison™ dose, or referral diagnosis. DISCUSSION: Our study showed that detection of VUR with ceVUS and Optison™ is comparable to fluoroscopic VCUG. Based on the VCUG reports, the incidence of VUR in our patient population was substantially lower than in the meta-analysis of Chua et al. and in the study of Kim et al. The explanation for the large discrepancy in VUR incidence may reflect differences in the patient populations, and in our reporting of VUR with respect to kidney number rather than to pelviureteral units. Study limitations include its retrospective nature and potential bias in terms of patient selection. Since VUR is an intermittent phenomenon, sequential rather than simultaneous performance of the ceVUS and fluoroscopic studies might have influenced VUR detection. CONCLUSION: A blinded comparison of ceVUS performed with Optison™ to fluoroscopic VCUG showed moderate-good sensitivity and specificity for diagnosis of VUR.

Copy Number Variation Analysis Facilitates Identification of Genetic Causation in Patients with Congenital Anomalies of the Kidney and Urinary Tract.

Background: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease among children and adults younger than 30 yr. In our previous study, whole-exome sequencing (WES) identified a known monogenic cause of isolated or syndromic CAKUT in 13% of families with CAKUT. However, WES has limitations and detection of copy number variations (CNV) is technically challenging, and CNVs causative of CAKUT have previously been detected in up to 16% of cases. Objective: To detect CNVs causing CAKUT in this WES cohort and increase the diagnostic yield. Design setting and participants: We performed a genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on the same CAKUT cohort for whom WES was previously conducted. Outcome measurements and statistical analysis: We evaluated and classified the CNVs using previously published predefined criteria. Results and limitations: In a cohort of 170 CAKUT families, we detected a pathogenic CNV known to cause CAKUT in nine families (5.29%, 9/170). There were no competing variants on genome-wide CNV analysis or WES analysis. In addition, we identified novel likely pathogenic CNVs that may cause a CAKUT phenotype in three of the 170 families (1.76%). Conclusions: CNV analysis in this cohort of 170 CAKUT families previously examined via WES increased the rate of diagnosis of genetic causes of CAKUT from 13% on WES to 18% on WES + CNV analysis combined. We also identified three candidate loci that may potentially cause CAKUT. Patient summary: We conducted a genetics study on families with congenital anomalies of the kidney and urinary tract (CAKUT). We identified gene mutations that can explain CAKUT symptoms in 5.29% of the families, which increased the percentage of genetic causes of CAKUT to 18% from a previous study, so roughly one in five of our patients with CAKUT had a genetic cause. These analyses can help patients with CAKUT and their families in identifying a possible genetic cause.

A truncating NRIP1 variant in an Arabic family with congenital anomalies of the kidneys and urinary tract.

Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of early-onset chronic kidney disease. In a previous study, we identified a heterozygous truncating variant in nuclear receptor-interacting protein 1 (NRIP1) as CAKUT causing via dysregulation of retinoic acid signaling. This large family remains the only family with NRIP1 variant reported so far. Here, we describe one additional CAKUT family with a truncating variant in NRIP1. By whole-exome sequencing, we identified one heterozygous frameshift variant (p.Asn676Lysfs*27) in an isolated CAKUT patient with bilateral hydroureteronephrosis and right grade V vesicoureteral reflux (VUR) and in the affected father with left renal hypoplasia. The variant is present twice in a heterozygous state in the gnomAD database of 125,000 control individuals. We report the second CAKUT family with a truncating variant in NRIP1, confirming that loss-of-function mutations in NRIP1 are a novel monogenic cause of human autosomal dominant CAKUT.

Whole-exome sequencing identifies FOXL2, FOXA2 and FOXA3 as candidate genes for monogenic congenital anomalies of the kidneys and urinary tract.

BACKGROUND: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of chronic kidney disease in the first three decades of life. Variants in four Forkhead box (FOX) transcription factors have been associated with CAKUT. We hypothesized that other FOX genes, if highly expressed in developing kidneys, may also represent monogenic causes of CAKUT. METHODS: We here performed whole-exome sequencing (WES) in 541 families with CAKUT and generated four lists of CAKUT candidate genes: (A) 36 FOX genes showing high expression during renal development, (B) 4 FOX genes known to cause CAKUT to validate list A, (C) 80 genes that we identified as unique potential novel CAKUT candidate genes when performing WES in 541 CAKUT families and (D) 175 genes identified from WES as multiple potential novel CAKUT candidate genes. RESULTS: To prioritize potential novel CAKUT candidates in the FOX gene family, we overlapped 36 FOX genes (list A) with lists C and D of WES-derived CAKUT candidates. Intersection with list C identified a de novo FOXL2 in-frame deletion in a patient with eyelid abnormalities and ureteropelvic junction obstruction, and a homozygous FOXA2 missense variant in a patient with horseshoe kidney. Intersection with list D identified a heterozygous FOXA3 missense variant in a CAKUT family with multiple affected individuals. CONCLUSIONS: We hereby identified FOXL2, FOXA2 and FOXA3 as novel monogenic candidate genes of CAKUT, supporting the utility of a paralog-based approach to discover mutated genes associated with human disease.

Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT.

PURPOSE: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES. METHODS: We conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping. RESULTS: In 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype-phenotype correlation. CONCLUSION: We conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.

Onabotulinumtoxin A (Botox): A reasonable alternative for refractory neurogenic bladder dysfunction in children and young adults.

AIMS: We aimed to describe the effectiveness of Onabotulinumtoxin A (Botox) in children with neurogenic bladder (NGB) unresponsive to medical therapy to determine urodynamic parameters predictive of success. METHODS: Children receiving Botox for refractory NGB, between 2008 and 2019, from a single academic center, were included in this study. Botox success was defined as improvement of incontinence and/or urodynamic parameters. RESULTS: Of 34 patients who received Botox, 13 (38.2%) had a positive response from their first injection, with improvement in capacity by a median of 35% of expected capacity for age compared to only a 9% increase in those who did not respond clinically. When patients were divided into groups by baseline urodynamic parameters, high-pressure (Pdetmax > 20 cm H2 O) patients had significantly greater improvement in compliance compared with low-pressure patients (p = 0.017). Low compliance patients (<10 ml/cm H2 O) had a dramatic improvement of 3.08 ml/cm H2 O in their compliance compared with minimal change in the high compliance group (p = 0.003). Finally, low-capacity (<50% of expected CC) patients had significant improvement in capacity and compliance when compared with high-capacity patients (p = 0.004 and p = 0.036, respectively). Improvement in detrusor overactivity (DO) was noted in both the clinical responders and non-responders. CONCLUSION: In our series, 38% had clinical success with intradetrusor Botox injections for refractory neurogenic bladder. When successful, improvement in capacity and compliance, DO, and/or incontinence was consistent with prior literature. While we could not determine which parameters predicted success, subdividing patients into categories based on baseline urodynamic parameters identified who would benefit from Botox treatment based on differential improvements in capacity and compliance. At least 1 injection of Botox should be considered for a subset of children with refractory NGB, before undertaking more invasive treatments.

The surface topography of silicone breast implants mediates the foreign body response in mice, rabbits and humans.

Silicone is widely used in chronic implants and is generally perceived to be safe. However, textured breast implants have been associated with immune-related complications, including malignancies. Here, by examining for up to one year the foreign body response and capsular fibrosis triggered by miniaturized or full-scale clinically approved breast implants with different surface topography (average roughness, 0-90 µm) placed in the mammary fat pads of mice or rabbits, respectively, we show that surface topography mediates immune responses to the implants. We also show that the surface surrounding human breast implants collected during revision surgeries also differentially alters the individual's immune responses to the implant. Moreover, miniaturized implants with an average roughness of 4 µm can largely suppress the foreign body response and fibrosis (but not in T-cell-deficient mice), and that tissue surrounding these implants displayed higher levels of immunosuppressive FOXP3+ regulatory T cells. Our findings suggest that, amongst the topographies investigated, implants with an average roughness of 4 µm provoke the least amount of inflammation and foreign body response.

Low energy availability and impact sport participation as risk factors for urinary incontinence in female athletes.

INTRODUCTION: Relative Energy Deficiency in Sport (RED-S) is a clinical syndrome that includes the many complex health and performance consequences of low energy availability (EA) in athletes, when there is insufficient caloric intake to meet exercise-related energy expenditure and to support basic physiologic functions. There is a high prevalence of urinary incontinence (UI) in female athletes and it is more common in female athletes than non-athletes. The objective of this study was to determine if low EA is associated with UI in a population of adolescent and young adult female athletes and to evaluate for an association between sport categories and UI. MATERIAL AND METHODS: 1000 nulliparous female patients, ages 15-30 years, presenting to a sports medicine subspecialty clinic, provided informed consent/assent to participate in a cross-sectional study involving a comprehensive survey, anthropomorphic measurements, and medical record review. Low EA was defined as meeting ≥1 criterion: self-reported history of eating disorder/disordered eating (ED/DE), and/or a high score on the Brief Eating Disorder in Athletes Questionnaire (BEDA-Q), and/or a high score on the Eating Disorder Screen for Primary Care (ESP). UI was assessed using questions adapted from the International Consultation on Incontinence-Urinary Incontinence Short Form (ICIQ-UI-SF), questions regarding timing of UI onset/duration, and a binary question regarding UI during sport activities. A total of 36 sport types were included in the survey and sub-divided into categories. RESULTS AND DISCUSSION: Of the 1000 female athletes surveyed, 165 (16.5%) reported a history of experiencing UI during athletic activities. ICIQ- UI-SF responses indicated that 14% (137/1000) of the cohort experienced slight incontinence, 4% (35/1000) moderate incontinence, and 2 athletes experienced severe incontinence. There was a significant difference between UI categories in age (p = 0.01), low EA (p < 0.001), and sport category (p < 0.001). Females who had low EA had twice the likelihood (OR = 1.97; 95% CI = 1.39 to 2.81; p < 0.001) of UI compared to those with adequate EA, controlling for sports category and menstrual dysfunction. Females who participated in high impact sports were 4.5 times more likely (OR = 4.47; 95% CI = 2.29 to 8.74; p < 0.001) to have had UI compared to females who participated in ball sports, controlling for EA and menstrual dysfunction. CONCLUSIONS: UI during athletic activities is a common problem among nulliparous adolescent and young adult female athletes, occurring in 16.5% of female athletes surveyed. UI was significantly associated with low EA across all sport categories. Sport type was significantly associated with UI, with the highest impact sport group demonstrating a higher prevalence and symptom severity compared to other sport categories.

Losartan prevents bladder fibrosis and protects renal function in rat with neurogenic paralysis bladder.

AIMS: To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB). MATERIALS AND METHODS: Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (Pves.leak ) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (Pves.thre ) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin Ⅱ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor ß1 (TGFß1), Collagen Ⅲ, and collagen fibrin in the bladder tissue were detected too. RESULTS: ΔC in TSNG and LSTG decreased significantly compared to the CG. Pves.leak in TSNG and LSTG were significantly higher than Pves.thre in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang Ⅱ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFß1, Collagen Ⅲ, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG. CONCLUSION: Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFß1 and consequently may reduce kidney damage from occurring.