Long-Term Patient-Reported Outcomes following Oncological Facial Reconstructive Surgery using the FACE-Q Skin Cancer Module.

Background: Long-term patient-reported outcomes (PROs) of oncological facial reconstructive surgery are unknown. Objective: The present study aimed to assess long-term PROs and to identify possible correlations between patient and treatment characteristics and long-term PROs. Methods & Materials: Between 2006 and 2011, 202 patients underwent facial reconstruction after Mohs micrographic surgery for non-melanoma skin cancer at our institution. After 10 years of follow-up, 96 out of the remaining 122 patients completed the FACE-Q Skin Cancer Module. Results: Patients who were surgically treated for squamous cell carcinoma reported poorer scores on the satisfaction with facial appearance (p=0.038), appraisal of scars (p=0.039) and appearance-related psychosocial distress scales (p=0.036) compared to patients with basal cell carcinoma and lentigo maligna. Finally, female patients reported significantly higher scores on the Cancer Worry Scale than male patients (p=0.047). Conclusion: Long-term patient satisfaction with respect to their facial appearance and scars after reconstructive surgery for skin cancer was comparable to short-term patient satisfaction, whereas Cancer Worry Scale and psychosocial distress appeared to be slightly higher. Our results can be used to better inform patients on the long-term effects of facial reconstructive surgery on patient satisfaction and quality of life, which are important to improve patient counselling, patient expectation management and shared decision-making.

Development of a highly sensitive and specific intact proviral DNA assay for HIV-1 subtype B and C.

INTRODUCTION: HIV reservoir quantification is essential for evaluation of HIV curative strategies and may provide valuable insights about reservoir dynamics during antiretroviral therapy. The Intact Proviral DNA Assay (IPDA) provides the unique opportunity to quantify the intact and defective reservoir. The current IPDA is optimized for HIV-1 subtype B, the dominant subtype in resource-rich settings. However, subtype C is dominant in Sub-Saharan Africa, jointly accounting for around 60% of the pandemic. We developed an assay capable of quantifying intact and defective proviral HIV-1 DNA of subtype B and C. METHODS: Primer and probe sequences were strategically positioned at conserved regions in psi and env and adapted to subtype B&C. In silico analysis of 752 subtype B and 697 subtype C near-full length genome sequences (nFGS) was performed to predict  the specificity and sensitivity. Gblocks were used to determine the limit of blank (LoB), limit of detection (LoD), and different annealing temperatures were tested to address impact of sequence variability. RESULTS: The in silico analysis showed that the HIV-1 B&C IPDA correctly identified 100% of the intact subtype B, and 86% of the subtype C sequences. In contrast, the original IPDA identified 86% and 12% of these subtype B and C sequences as intact. Furthermore, the HIV-1 B&C IPDA correctly identified hypermutated (87% and 88%) and other defective sequences (73% and 66%) for subtype B and C with comparable specificity as the original IPDA for subtype B (59% and 63%). Subtype B cis-acting sequences were more frequently identified as intact by the HIV-1 B&C IPDA compared to the original IPDA (39% and 2%). The LoB for intact proviral DNA copies was 0, and the LoD for intact proviral DNA copies was 6 (> 95% certainty) at 60 °C. Quantification of 2-6 copies can be performed with > 80% certainty. Lowering the annealing temperature to 55 °C slightly lowered the specificity but prevented exclusion of samples with single mutations in the primer/probe region. CONCLUSIONS: We developed a robust and sensitive assay for the quantification of intact and defective HIV-1 subtype B and C proviral DNA, making this a suitable tool to monitor the impact of (large-scale) curative interventions.

Flat Γ Moiré Bands in Twisted Bilayer WSe_{2}.

The recent observation of correlated phases in transition metal dichalcogenide moiré systems at integer and fractional filling promises new insight into metal-insulator transitions and the unusual states of matter that can emerge near such transitions. Here, we combine real- and momentum-space mapping techniques to study moiré superlattice effects in 57.4° twisted WSe_{2} (tWSe_{2}). Our data reveal a split-off flat band that derives from the monolayer Γ states. Using advanced data analysis, we directly quantify the moiré potential from our data. We further demonstrate that the global valence band maximum in tWSe_{2} is close in energy to this flat band but derives from the monolayer K states which show weaker superlattice effects. These results constrain theoretical models and open the perspective that Γ-valley flat bands might be involved in the correlated physics of twisted WSe_{2}.

Altered lipid metabolism in synovial fibroblasts of individuals at risk of developing rheumatoid arthritis.

OBJECTIVE: Fibroblast-like synoviocytes (FLS) can augment the inflammatory process observed in synovium of patients with rheumatoid arthritis (RA). A recent transcriptomic study in synovial biopsies revealed changes in metabolic pathways before disease onset in absence of synovial tissue inflammation. This raises the question whether alterations in cellular metabolism in tissue resident FLS underlie disease pathogenesis. MATERIALS AND METHODS: To study this, we compared the metabolic profile of FLS isolated from synovial biopsies from individuals with arthralgia who were autoantibody positive but without any evidence of arthritis (RA-risk individuals, n = 6) with FLS from patients with RA (n = 6), osteoarthritis (OA, n = 6) and seronegative controls (n = 6). After synovial digestion, FLS were cultured in vitro and cellular metabolism was assessed using quantitative PCR, flow cytometry, XFe96 Seahorse Analyzer and tritium-labelled oleate oxidation assays. RESULTS: Real-time metabolic profiling revealed that basal (p < 0.0001) and maximum mitochondrial respiration (p = 0.0024) were significantly lower in RA FLS compared with control FLS. In all donors, basal respiration was largely dependent on fatty acid oxidation while glucose was only highly used by FLS from RA patients. Moreover, we showed that RA-risk and RA FLS are less metabolically flexible. Strikingly, mitochondrial fatty acid ß-oxidation was significantly impaired in RA-risk (p = 0.001) and RA FLS (p < 0.0001) compared with control FLS. CONCLUSION: Overall, this study showed several metabolic alterations in FLS even in absence of synovial inflammation, suggesting that these alterations already start before clinical manifestation of disease and may drive disease pathogenesis.

Newborns with myelomeningocele: their health-related quality of life and daily functioning 10 years later.

OBJECTIVE: Ten years ago, the authors reported on the outcome of their study investigating the degree of discomfort and pain in newborns with myelomeningocele (MMC), using the parameters of unbearable and hopeless suffering. In the current study, they investigated the quality of life, daily functioning, pain and fatigue, ability to communicate, and number of surgeries in the same cohort of patients. They subdivided their study population into severe (Lorber) and less severe (non-Lorber) cases and compared these cases with a healthy population (non-MMC group) and with each other. METHODS: The parents of 22 of 28 patients gave informed consent for this study. The KIDSCREEN-27 and PEDI-CAT (Pediatric Evaluation of Disability Inventory) were used to assess quality of life and daily functioning. Pain and fatigue were self-reported on a 10-point numeric rating scale. Communication and ambulation levels were determined using the Communication Function Classification System (CFCS) and the Hoffer ambulation scale. Using reference data from the KIDSCREEN-27 and PEDI-CAT, the authors created a healthy population comparison group. RESULTS: There was no significant difference in health-related quality-of-life (HRQOL) scores between Lorber and non-Lorber patients, except that school environment domain scores were lower in the Lorber group. When comparing the HRQOL of MMC patients with that of the non-MMC group, the physical well-being and parent relations and autonomy domains scored significantly lower. The daily functioning of MMC patients was lower on all domains of the PEDI-CAT compared with the non-MMC group. Lorber MMC patients scored lower on all domains of the PEDI-CAT when compared with non-Lorber patients. All patients were capable of communicating effectively; most patients (n = 18) were considered CFCS level I, and 4 patients were considered CFCS level II. CONCLUSIONS: This study shows that MMC is a severe, lifelong condition that affects patients' lives in many domains. All the patients in this study are capable of effective communication, irrespective of severity of MMC. Overall, the data show that in newborn MMC patients, future unbearable suffering with respect to pain, mobility, cognition, and communication is hard to predict and may not always occur.

Long-term quality of life and aesthetic outcomes after breast conserving surgery in patients with breast cancer.

INTRODUCTION: Breast surgery has become less invasive without compromising survival and aimed at improving quality of life (QoL) in terms of satisfaction with cosmesis. Despite that, short-term patient-perceived aesthetic results after breast-conserving surgery (BCS) can still be displeasing. Long-term analysis regarding contentment with cosmesis are lacking and could be different, considering that over time, patients' priorities might change and a different thought-out judgment could be given. The goal of this study is to describe long-term results in QoL after BCS and to identify possible predictors for disappointing aesthetic results. METHODS: In this retrospective cohort study, the long-term outcomes of QoL, patient-reported outcome measurements and aesthetic outcomes were investigated 4.5-10.8 years after BCS. In total, 104 patients received standardized questionnaires from the European Organisation of Research and Treatment of Cancer. The aesthetic results after BCS were evaluated subjectively through a diverse panel of healthcare observers. Objective assessment of the aesthetic results was done using the BCCT.core system of evaluating standardised breast photographs. Factors influencing aesthetic outcome were statistically analysed. RESULTS: QoL was high in around 75% of the patients. Correlation between QoL and aesthetic outcomes was found according to Spearman's correlation (r = 0.262, p = 0.007). Significant factors negatively influencing patient reported aesthetic outcomes were sentinel node procedure (p = 0.016), axillary lymph node dissection (p = 0.004), chemotherapy (p = 0.001), and hormonal therapy (p = 0.001). CONCLUSION: The majority of the patients have acceptable QoL after BCS during long-term follow-up. Unacceptable aesthetic outcomes after BCS are associated with lower QoL and are influenced by sentinel node procedure, axillary lymph node dissection, chemotherapy, and hormonal therapy.

Quantitative analysis of spectroscopic low energy electron microscopy data: High-dynamic range imaging, drift correction and cluster analysis.

For many complex materials systems, low-energy electron microscopy (LEEM) offers detailed insights into morphology and crystallography by naturally combining real-space and reciprocal-space information. Its unique strength, however, is that all measurements can easily be performed energy-dependently. Consequently, one should treat LEEM measurements as multi-dimensional, spectroscopic datasets rather than as images to fully harvest this potential. Here we describe a measurement and data analysis approach to obtain such quantitative spectroscopic LEEM datasets with high lateral resolution. The employed detector correction and adjustment techniques enable measurement of true reflectivity values over four orders of magnitudes of intensity. Moreover, we show a drift correction algorithm, tailored for LEEM datasets with inverting contrast, that yields sub-pixel accuracy without special computational demands. Finally, we apply dimension reduction techniques to summarize the key spectroscopic features of datasets with hundreds of images into two single images that can easily be presented and interpreted intuitively. We use cluster analysis to automatically identify different materials within the field of view and to calculate average spectra per material. We demonstrate these methods by analyzing bright-field and dark-field datasets of few-layer graphene grown on silicon carbide and provide a high-performance Python implementation.

Modelling fungal hypha tip growth via viscous sheet approximation.

In this paper we present a new model for single-celled, non-branching hypha tip growth. The growth mechanism of hypha cells consists of transport of cell wall building material to the cell wall and subsequent incorporation of this material in the wall as it arrives. To model the transport of cell wall building material to the cell wall we follow Bartnicki-Garcia and Gierz in assuming that the cell wall building material is transported in straight lines by an isotropic point source. To model the dynamics of the cell wall, including its growth by new material, we use the approach of Campàs and Mahadevan, which assumes that the cell wall is a thin viscous sheet sustained by a pressure difference. Furthermore, we include a novel equation which models the hardening of the cell wall as it ages. We validate the new model by comparing it to experimental data.

Cowper's syringocele in the pediatric population: a retrospective study of 122 patients.

INTRODUCTION AND OBJECTIVE: Syringocele is a rare cystic dilatation of the duct of Cowper's gland, afflicting mostly the pediatric population. Syringoceles have a wide range of symptoms and may cause urethral obstruction. The authors analyzed to clarify the clinical manifestation, diagnostic approach, management, and incidence in the pediatric population. MATERIALS AND METHODS: All patients (122 cases) diagnosed with a syringocele at the department of Pediatric Urology in a tertiary referral university children's hospital between August 1991 and October 2016 were analyzed retrospectively by assessing medical charts. RESULTS: The clinical manifestation, diagnostic findings, and follow-up are summarized in the table. Half of the patients (50.0%) also had typical posterior urethral valves (PUVs) and/or a single valve in the 12 o'clock position (flap-valve). The symptoms of open and closed syringoceles showed no significant difference. Treatment consisted of incision of the syringocele with a diathermia hook. The incidence of urinary tract infection (UTI) before and after surgery in the group that had a syringocele only was significant different. The overall incidence of syringoceles seen at urethrocystoscopy in this series was 3.0%. DISCUSSION: This series suggests that the presenting age is strongly related to the consequences of syringoceles, as the youngest half of the patients had significantly more UTIs at presentation than older patients, who presented with significantly more obstructive voiding symptoms, postvoiding residuals, and incontinence. In addition, the younger group had a significantly higher incidence of vesicoureteral reflux and dilatation of the upper urinary tract. The found association between syringoceles and PUV may be due to overgrowth of epithelium, as possible origin in both anomalies. CONCLUSION: With an incidence of 3.0%, syringoceles, in this tertiary referral series, should be considered in the differential diagnosis of obstructive urethral lesions. The presentation ranges between signs of severe obstructions in the prenatal and postnatal period to mild urinary incontinence problems at later age. Urethrocystoscopy proved to be useful in confirming the diagnosis and allows for immediate transurethral incision.

[Diagnosis and treatment of fracture-related infections]. / Diagnostiek en behandeling van fractuur-gerelateerde infecties.

Fracture-related infection (FRI) is a serious complication after fracture care and can lead to severe morbidity with loss of quality of life, a significant increase in medical expenses and loss of participation in work and social life. Early recognition, adequate surgical debridement, deep uncontaminated tissue cultures with (if indicated) soft tissue reconstruction and fracture stabilization followed by antibiotic therapy are the cornerstones of the successful management of FRI. Recently, in 2018, the AO/EBJIS consensus definition for FRI was published and both national and international working groups are being assembled and provide guidelines and tools for the care of patients with FRI. This paper is a synopsis of the Dutch guideline on FRI (2018), illustrated by a clinical case, and is aiming to provide an overview of the current knowledge on diagnosis and treatment of this disease.

[To act or not to act? Developments in prenatal and postnatal care for children with spina bifida aperta]. / Handelen of niet handelen?

To act or not to act? Developments in prenatal and postnatal care for children with spina bifida aperta Until the middle of the twentieth century, newborns with spina bifida aperta had low chances of survival. Advances in the treatment of hydrocephalus, among other conditions, led to increased chances of survival during the 1960s. This also revealed the downsides of the treatment of spina bifida patients since some considered the quality of life of a number of these patients to be unacceptable. But withholding treatment also had negative consequences, leading to an ethical deadlock. Over the past thirty years - besides postnatal closure of the neural tube defect - more emphasis has been put on selective pregnancy termination and sporadic active termination of life in newborns with very severe forms of spina bifida. At the same time, new treatment strategies, such as foetal surgery, are being developed. With this historical overview, we illustrate the way in which technological developments and ethical dilemmas are constantly affecting each other.

Comparison of preputioplasty and circumcision in distal hypospadias correction: long-term follow-up.

OBJECTIVE: A normal penile cosmesis is an important goal in distal hypospadias repair. Depending on cultural standards, repairs are combined with a preputioplasty or circumcision to attain a 'normal' penile appearance. Although short-term complication rates of preputioplasty are available, data on long-term outcomes are scarce. Therefore, this study assessed long-term functional and cosmetic outcomes of distal hypospadias repair with either a preputioplasty or a circumcision. PATIENTS AND METHODS: Eligible for inclusion were patients with distal hypospadias operated in childhood between 1987 and 1993. Complications and reasons for secondary circumcision were extracted from the medical charts. Participants completed a questionnaire including the International Index of Erectile Function (IIEF-15), the International Prostate Symptom score (IPSS), and additional non-validated questions. Penile cosmesis was judged with the Penile Perception Score (PPS), stretched penile length was measured, and uroflowmetry was performed. RESULTS: Of the 86 eligible and traceable patients, 40 (47%) participated; of them, 27 had a preputioplasty and 13 a circumcision. Six patients underwent a secondary circumcision due to a preputial defect (n = 2), unsatisfactory cosmetic result (n = 2), religious reason (n = 1), or phimosis (n = 1). Complication rates were similar in both the groups. Long-term outcomes in the preputioplasty and circumcision group were comparable regarding cosmetic, sexual, and micturition outcomes. CONCLUSIONS: Distal hypospadias correction combined with preputioplasty had complication rates similar to those of hypospadias repair with circumcision. In these patients, preputioplasty had a failure rate of 22%. In both the groups, long-term outcomes of urinary function, sexual function, and cosmesis were good.

Does a serious game increase intrinsic motivation in children receiving urotherapy?

INTRODUCTION: Urotherapy is considered the treatment of choice for children suffering daytime urinary incontinence (DUI). Urotherapy intends to improve bladder dysfunction for children with DUI. For children with refractory DUI, an intensive inpatient bladder training program exists, which focuses on relearning, concentration on, and awareness of the bladder. Children's motivation and adherence are key determinants of a successful training outcome. It is hypothesized that motivation endurance throughout the treatment process may be enhanced by a serious game training tool, which could make the training more appealing and rewarding. OBJECTIVE: The study explores intrinsic motivation in children receiving bladder training for DUI and whether using a serious game improves their intrinsic motivation. STUDY DESIGN: In this pragmatic study, 50 children were allowed to choose among receiving bladder training with (intervention group) or without the application of a serious game (control group). At 4, 8, and 12 weeks of training, children and parents were asked to complete the Intrinsic Motivation Inventory (IMI). Children also completed the Pediatric Urinary Incontinence Quality of Life Tool (PinQ) before the start of the training and 6 months thereafter. At 6-month follow-up, patients were ask to participate in two focus groups, wherein the children discussed how they used the serious game and which improvements they would prefer. RESULTS: Children who received standard bladder training with the addition of a serious game did not differ in terms of intrinsic motivation from children who underwent standard bladder training only. Training results were equal in both the groups, with 80% good or improved. Incontinence-related quality of life (QoL) improved accordingly. DISCUSSION: In contrast to the study expectations, this game did not increase intrinsic motivation. Findings on training and QoL results are consistent with those of previous studies in both interventions. Although a randomized design could have yielded more valid results than this preference-based approach, the latter is more congruent with clinical practice. In contrast to existing bladder diary apps, this game offers a combination of child-friendly instructions, explanation of bladder (dys)function, and keeping a bladder diary. Mobile devices are playing an increasingly important role in health care; therefore, an urotherapy app can be a complementary therapeutic tool. CONCLUSION: Most children find it attractive to combine bladder training with a serious game. However, no added value was found regarding intrinsic motivation and training results. All children with persistent DUI in this cohort were highly motivated to complete an intensive bladder training program.

SENS-U: validation of a wearable ultrasonic bladder monitor in children during urodynamic studies.

PURPOSE: Urinary incontinence is a common problem in school-age children. Because many children remain unaware of a full-bladder sensation, the SENS-U™ Bladder Sensor was developed. The SENS-U is a small, wearable ultrasound sensor, which is positioned on the lower abdomen using a skin-friendly adhesive. The sensor continuously estimates the bladder filling status and informs the user when it is time to go to the toilet. In this study, the clinical performance of the SENS-U is evaluated in children during (video) urodynamics. MATERIAL AND METHODS: In this study, 30 children (6-12 years) were included who were scheduled for a (video) urodynamic study. During urodynamics, the SENS-U determined the average anterior-posterior (A-P) bladder dimension (every 30 s) to estimate the filling status. The correlation between the average A-P bladder dimension and the infused volume is analyzed by Spearman's correlation. RESULTS: Thirty patients (boys/girls: 15/15; mean age: 7.9 ± 1.4 years) were included, in whom the SENS-U detected the full bladder before voiding in 90% of the patients (27/30). In the other patients, the bladder was outside the detection area due to either erroneous sensor placement (n = 1) or an (relative) obese abdomen in the upright position (n = 2). There was a strong correlation (median rs = 0.94) between the average A-P bladder dimension and the infused volume. The detectable maximum bladder volume ranged between 71 and 463 ml. CONCLUSION: The SENS-U is able to detect a full bladder with a success rate of 90%. When excluding erroneous data due to sensor misplacement or an (relative) obese abdomen, the detection rate may even be higher. Future research will focus on investigating the effect of theSENS-U in incontinence training.

The Double Dutch technique: A new way of creating an ileocystoplasty with a lengthy catheterizable ileal tube.

INTRODUCTION: A tubularized conduit from an open 2-cm vascularized ileal segment is a frequently used technique to create a continent catheterizable channel in cases of an inappropriate or absent appendix. In the long term, many patients experience catheterization problems with the classic ileal segment tube, and even more with spiral or double-segment tubes. OBJECTIVE: The objective of this paper was to introduce an ileocystoplasty modification combined with a long ileal segment tube that has better support by surrounding tissue than other lengthy ileal segment tubes. Briefly summarized, this newly introduced method begins with isolating approximately 30 cm of ileum and dividing it into two parts. Two strips are then created and closed as a double-length tube. The ileal segments are opened antimesenterically and closed over the tube in the middle. The lower part of the tube is implanted with a submucosal tunnel in the bladder wall, and the ileal patch is then anastomosed with the bladder. The tube is anastomosed to the umbilicus in an ordinary way without any traction (see Summary Fig.). STUDY DESIGN: Between May 2005 and November 2012 the new technique was used at the current institution in nine children who needed an ileocystoplasty (mean age: 9 years and 3 months). Underlying etiology was neurogenic bladder in seven cases and epispadias in two. RESULTS: All patients ultimately had stomas without leakage or strictures. During follow-up, three of nine tubes developed stenoses that were corrected; four stomas in total had some sort of surgical revision. Median follow-up was 93 months. Intermittent catheterization was uncomplicated in all at this time. DISCUSSION: With this modification of the standard technique it seemed to be possible to create a more stable channel. The blood supply of the tube was secured by completely embedding the mesentery of the tube. Limitations included the small number of patients treated so far. CONCLUSION: The lengthy tubes appeared to be straight and well supported by the surrounding tissues, which prevented kinking and sacculation. It is hoped that this technique will have better results and fewer complications at long-term follow-up.

Performance of aneuploid backcross hybrids between the crop Brassica napus and its wild relative B. rapa.

Crossings between the diploid wild Brassica rapa (AA, 2n = 20) and the tetraploid cultivar B. napus (AACC, 2n = 38) can readily be made. Backcrosses to the wild B. rapa (BC1 ) produce aneuploids with variable chromosome numbers between 20 and 29. How does survival and performance relate to DNA content of plants? Growth of the BC1 plants was measured in the lab. One plant in the F1 self-pollinated spontaneously and produced abundant F2 seeds that were also examined. The number of C-chromosomes was estimated from DNA values obtained with flow cytometry. Average DNA value of the BC1 was similar to that of the parents, which shows that C-chromosomes do not reduce success of pollen or embryos. The average DNA value in the F2 was 13% higher than in the F1 , suggesting that extra C-chromosomes facilitated gamete success and/or embryo survival. Under both optimal and drought stress conditions growth and survival of BC1 hybrids was similar to that of B. rapa. No significant correlations existed between growth or survival and DNA value. Aneuploid plants were not inferior under the conditions of the growth room and may persist in nature. We discuss other factors, such as herbivory, that could prevent hybrid establishment in the field.

Minimally Invasive, Spring-Assisted Correction of Sagittal Suture Synostosis: Technique, Outcome, and Complications in 83 Cases.

BACKGROUND: This series describes the results of minimally invasive strip craniotomy with additional spring distraction. METHODS: Included are the first 83 consecutive patients who underwent this procedure (January 1, 2010, to January 1, 2014). Outcome parameters were collected prospectively and included surgical parameters and complications, the occurrence of papilledema, skull growth, cephalic index, and photographic scores. RESULTS: Duration of surgery was 63 minutes, 19 percent required blood transfusion, and complications were minor. Postoperative papilledema occurred in two patients (2.4 percent). Head growth increased after insertion of the springs and declined afterward to 0.7 SD, comparable to earlier cohorts in the authors' center. The cephalic index increased from 67 before surgery to 74 after surgery and showed a small decrease during the 4-year follow-up. Photographic scores confirmed the initial improvement and showed a trend to further improvement during follow-up. CONCLUSIONS: In this cohort, spring-assisted, minimally invasive strip craniotomy was safe and effective. Results were similar to those from other techniques but with smaller incisions, shorter interventions, reduced blood loss, and a lower incidence of postoperative papilledema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Testosterone prior to hypospadias repair: Postoperative complication rates and long-term cosmetic results, penile length and body height.

INTRODUCTION: The use of hormonal therapy was first described in 1971 before hypospadias surgery, and it has been debated ever since. The long-term outcomes after puberty of patients treated with pre-operative testosterone in childhood are lacking. OBJECTIVES: Possible long-term effects of testosterone are often asked about in daily practice. The current study investigated the long-term outcomes regarding height, penile length and penile cosmesis in adult men after hypospadias surgery in childhood with and without pre-operative testosterone. METHODS: Adult men (n = 121) who underwent primary hypospadias repair in childhood were included. Pre-operative penile appearance, judged by a paediatric urologist, determined the use of pre-operative testosterone. Data on hypospadias characteristics, healing complications, surgical repair, and testosterone use were collected retrospectively. At adult age, stretched penile length and body height were measured, and penile cosmesis was evaluated using the Pediatric Penile Perception Score (PPPS). RESULTS: Postoperative complication rates in patients (n = 121) with and without testosterone were similar (50% vs. 43%; P = 0.54). Sixty adult patients (50%) with a median age of 19.8 years and follow-up time of 18.3 years were examined at the outpatient clinic at adult age. Of this group, testosterone was applied in 12/43 patients with distal, 3/6 patients with midshaft, and 9/11 patients with proximal hypospadias. Adult stretched penile length (12.0 cm vs. 12.4 cm; P = 0.47) and adult height (180.1 cm vs. 179.0 cm P = 0.65) showed no difference between patients with and without testosterone treatment. Penile cosmesis was (very) satisfactory in all PPPS domains, and showed no difference between the testosterone group and the non-testosterone group. Univariate and multivariate analysis was conducted to determine if the hypospadias type or pre-operative testosterone therapy had more influence on the long-term outcomes. None of the long-term outcomes were significantly associated with pre-operative testosterone therapy on multivariate analysis. DISCUSSION: This was the first study reporting long-term outcomes of hypospadias patients after puberty who received pre-operative hormonal therapy. Validated instruments were used as much as possible. Shortcomings of this study were the 50% response rate, the retrospective design, and the lack of objective inclusion criteria reported to indicate pre-operative testosterone therapy. CONCLUSION: This study suggested that the long-term results of patients receiving pre-operative testosterone treatment, who often had more challenging hypospadias, were similar to those who did not. However, a randomised controlled study is needed to confirm these results.

Urban-rural inequalities in suicide mortality: a comparison of urbanicity indicators.

BACKGROUND: Urban-rural disparities in suicide mortality have received considerable attention. Varying conceptualizations of urbanity may contribute to the conflicting findings. This ecological study on Germany assessed how and to what extent urban-rural suicide associations are affected by 14 different urban-rural indicators. METHODS: Indicators were based on continuous or k-means classified population data, land-use data, planning typologies, or represented population-based accessibility indicators. Agreements between indicators were tested with correlation analyses. Spatial Bayesian Poisson regressions were estimated to examine urban-rural suicide associations while adjusting for risk and protective factors. RESULTS: Urban-rural differences in suicide rates per 100,000 persons were found irrespective of the indicator. Strong and significant correlation was observed between different urban-rural indicators. Although the effect sign consistently referred to a reduced risk in urban areas, statistical significance was not universally confirmed by all regressions. Goodness-of-fit statistics suggested that the population potential score performs best, and that population density is the second best indicator of urbanicity. Numerical indicators are favored over classified ones. Regional planning typologies are not supported. CONCLUSIONS: The strength of suicide urban-rural associations varies with respect to the applied indicator of urbanicity. Future studies that put urban-rural inequalities central are recommended to apply either unclassified population potentials or population density indicators, but sensitivity analyses are advised.