Effect of early vs. delayed extubation on functional outcome among patients with acute ischemic stroke treated with endovascular thrombectomy under general anesthesia: the prospective, randomized controlled EDESTROKE trial study protocol.

BACKGROUND: Recent meta-analyses and randomized studies have shown that among patients with acute ischemic stroke undergoing endovascular thrombectomy, general anesthesia with mechanical ventilation is associated with better functional status compared to local anesthesia and sedation, and they recommend its use. But once the procedure is completed, when is the optimal moment for extubation? Currently, there are no guidelines recommending the optimal moment for extubation. Prolonged mechanical ventilation time could potentially be linked to increased complications such as pneumonia or disturbances in cerebral blood flow due to the vasodilatation produced by most anesthetic drugs. However, premature extubation in a patient who has suffered a stroke could led to complications such as agitation, disorientation, abolished reflexes, sudden fluctuations in blood pressure, alterations in cerebral blood flow, respiratory distress, bronchial aspiration, and the need for reintubation. We therefore designed a randomized study hypothesizing that early compared with delayed extubation is associated with a better functional outcome 3 months after endovascular thrombectomy treatment under general anesthesia for acute ischemic stroke. METHODS: This investigator-initiated, single-center, prospective, parallel, evaluated blinded, superiority, randomized controlled trial will include 178 patients with a proximal occlusion of the anterior circulation treated with successful endovascular thrombectomy (TICI 2b-3) under general anesthesia. Patients will be randomly allocated to receive early (< 6 h) or delayed (6-12 h) extubation after the procedure. The primary outcome measure is functional independence (mRS of 0-2) at 90 days, measured with the modified Rankin Score (mRS), ranging from 0 (no symptoms) to 6 (death). DISCUSSION: This will be the first trial to compare the effect of mechanical ventilation duration (early vs delayed extubation) after satisfactory endovascular thrombectomy for acute ischemic stroke under general anesthesia. TRIAL REGISTRATION: The study protocol was approved April 11, 2023, by the by the Santiago-Lugo Research Ethics Committee (CEI-SL), number 2023/127, and was registered into the clinicaltrials.gov clinical trials registry with No. NCT05847309. Informed consent is required. Participant recruitment begins on April 18, 2023. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

Long-term outcome of pediatric renal transplantation with donors younger than 6 years.

BACKGROUND: Renal transplantation is currently the best treatment option for patients with end-stage renal disease. However, the use of kidneys from donors under 6 years of age as a possibility to increase the organ pool in pediatric recipients remains a controversial matter. We aimed to investigate whether donor age is associated to the long-term functionality of the renal graft. Likewise, we analyzed the adaptation of the graft to the ascending functional requirements in the pediatric patient. METHODS: Retrospective study of the results obtained in pediatric recipients transplanted with grafts from donors between 3 and 6 years of age, comparing them with those of grafts from donors older than 6 years. Among the variables compared are cumulative graft survival, renal size, need for antiproteinuric therapy, GFR, incidence of rejection, pyelonephritis, renal failure and surgical or tumor complications. RESULTS: A total of 43 transplants were performed with donors aged 3-6 years, and 42 transplants with donors older than 6 years. Cumulative graft survival at 5 years was 81% for the younger donor group compared to 98% for the older donor group (p < .05). At 8 years, cumulative graft survival for donors <6 years was 74%. As for the mean estimated graft survival, it was 11.52 years for the younger donor group and 14.51 years for older donors. During follow-up, the younger donor group presented greater renal enlargement and need for antiproteinuric therapy. The older donors group had a higher GFR during the first year of follow-up, which then equalized in both groups. There were no statistically significant differences in the incidence of acute or chronic rejection, acute pyelonephritis, acute renal failure or surgical or tumor complications. CONCLUSIONS: Renal transplants of grafts equal to or less than 6 years old have good short-term and acceptable long-term results in pediatric patients.

Intention to use physical restraint in paediatric intensive care units and correlated variables: A multicentre and cross-sectional study.

OBJECTIVES: To determine the intention to use physical restraint (PR) and the relationship with sociodemographic and professional variables of the Paediatric Intensive Care Unit (PICU) nurses. RESEARCH METHODOLOGY/DESIGN AND SETTING: A multicentre and correlational study was carried out from October 2021 to December 2023 in five paediatric intensive care units from five maternal and child hospitals in Spain. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire was provided. Moreover, sociodemographic and employment variables were registered. RESULTS: A total of 230 paediatric nurses participated in the study. A total of 87.7 % were females with an average age of 35.5 ± 9.7 years and working experience of 10.5 ± 8.4 years. The mean scores obtained were 21.1 ± 3.8 for attitude, 13.1 ± 5.0 for subjective norms, 14.4 ± 4.3 for perceived behavioural control and 28.0 ± 6.0 for intention. The nurses apply more physical restraint to anxious patients, with scarce analgesics and sedation, those affected with pharmacological withdrawal symptoms and those with a high risk of accidental removal of vital support devices or fall from bed. The sex (p = 0.007) and type of employment contract (p = 0.01) are the variables that are significantly correlated with the intention to use of PR. CONCLUSION: The paediatric nurses analysed had a moderate attitude, social pressure and perceived behavioural control towards the use of PR. IMPLICATIONS FOR CLINICAL PRACTICE: It is important to know the factors that influence the intention to use physical restraint in order to standardise safe practice for critically ill paediatric and to ensure that patients' rights are respected by obtaining informed consent and assessing the prescription, continuation and removal of physical restraint.

Adaptation and validation of the Physical Restraint-Theory of Planned Behaviour Questionnaire to the paediatric context.

OBJECTIVE: To create and test psychometrically a paediatric version of the Physical Restraint-Theory of Planned Behaviour Questionnaire to assess paediatric critical care nurses' intention to use physical restraint. DESIGN: A psychometric study. SETTING: Five medical-surgical Paeditric Intensive care Units from five hospitals in Spain. METHODS: The study took place in three phases. In phase 1, the questionnaire was adapted. In phase 2, the content validity of each item was determined, and a pilot test was conducted. In phase 3, we administered the questionnaire and determined its psychometric properties. RESULTS: The assessment of the intention to use physical restraint was extended to all critical paediatric patients, two items were eliminated from the initial questionnaire, four new items were included, and the clinical scenarios of the intention subscale were expanded from three to six. Overall content validity index for the full instrument of 0.96 out of 1. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire is made up of four subscales (attitude, subjective norms (SN), perceived behavioural control (PBC), and intention) subdivided into 7 factors and 51 items. The internal consistency for the attitude subscale obtained a Cronbach's Alpha of 0.80 to 0.73, for the SN it was 0.72 to 0.89, for the PBC it was from 0.80 to 0.73 and for the intention subscale it was 0.75. CONCLUSIONS: The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire is an instrument composed of seven factors and 51 items that validly and reliably assesses the intention of paediatric nurses to apply PR in PICUs. RELEVANCE FOR CLINICAL PRACTICE: Having this instrument will help health centres move towards restraint-free care by allowing managers to assess professionals' attitudes, beliefs, and intentions around the use of PR in PICUs.

Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.

Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single bolus administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities of rtPA and TNK were evaluated in endothelial cells, astrocytes, and neuronal cells. In addition, their in vivo efficacy was independently assessed at two research centers using an ischemic thromboembolic mouse model. Both therapies were tested via early (20 and 30 min) and late administration (4 and 4.5 h) after stroke. rtPA, but not TNK, caused cell death only in neuronal cultures. Mice were less sensitive to thrombolytic therapies than humans, requiring doses 10-fold higher than the established clinical dose. A single bolus dose of 2.5 mg/kg TNK led to an infarct reduction similar to perfusion with 10 mg/kg of rtPA. Early administration of TNK decreased the hemorrhagic transformations compared to that by the early administration of rtPA; however, this result was not obtained following late administration. These two independent preclinical studies support the use of TNK as a promising reperfusion alternative to rtPA.

Neutrophil-to-lymphocyte ratio as a predictor of primary vesicoureteral reflux evolution in children with associated acute pyelonephritis.

Background: Neutrophil-to-lymphocyte ratio (NLR) has been recently postulated as an inflammatory biomarker for the diagnosis of vesicoureteral reflux (VUR). The aim of this study is to determine the role of NLR as a predictor of evolution of primary VUR in patients with associated acute pyelonephritis (APN). Methods: A retrospective observational cohort study was performed in patients with APN episodes with associated primary VUR diagnosed between 2013-2020. Patients were divided into two groups according to VUR evolution after APN: group A [spontaneous resolution (SR)] and group B [VUR complications development (CD) during follow-up: new APN or renal function worsening]. Demographic, prenatal, laboratory, microbiological and radiological data were analysed. Sensitivity and specificity for CD of VUR was determined by receiver operating characteristic (ROC) curves. Results: A total of 1,146 episodes of APN were analysed of which 273 patients with APN and associated primary VUR were finally included (median age of 11 months at APN diagnosis). SR of VUR occurred in 169 patients (SR group), while CD were observed in the remaining 104 patients (CD group). No differences in demographic, prenatal, microbiological and radiological features were observed. CD patients had significantly higher levels of leukocytes, neutrophils, NLR, C-reactive protein and creatinine. NLR was the parameter with the highest area under the curve (AUC =0.966) for predicting the development of VUR complications (cut-off point =3.41) with a maximum sensitivity of 92.7% and specificity of 91.1% (P<0.001). Conclusions: NLR may be considered as a simple and cost-effective predictor of clinical outcome of VUR, which may correlate with the increased risk of developing complications of primary VUR after an episode of APN. Therefore, it should be included in the management algorithm for these patients, although future prospective studies are still required to confirm these results.

Simultaneous bladder augmentation and artificial urinary sphincter placement in children with neuropathic urinary incontinence. Is it safe to perform? Long-term results.

INTRODUCTION: Simultaneous performance of artificial urinary sphincter (AUS) placement and bladder augmentation (BA) in patients with neuropathic bladder is currently controversial. OBJECTIVE: The aim of this study is to describe our very long-term results after a median follow-up of 17 years. STUDY DESIGN: A retrospective single-center case-control study was performed in patients with neuropathic bladder treated in our institution between 1994 and 2020, in whom AUS placement and BA were performed simultaneously (SIM group) or sequentially at different times (SEQ group). Demographic variables, hospital length of stay (LOS), long-term outcomes and postoperative complications were compared between both groups. RESULTS: A total of 39 patients (21 males, 18 females) were included, with a median age of 14.3 years. BA and AUS were performed simultaneously at the same intervention in 27 patients, and sequentially in different interventions in 12 cases, with a median of 18 months between both surgeries. No demographics differences were observed. SIM group had a shorter median LOS when compared to SEQ group, considering the two sequential procedures (10 vs. 15 days; p = 0.032). Median follow-up was 17.2 years (interquartile range 10.3-23.9). Four postoperative complications were reported, 3 patients in SIM group and 1 case in SEQ group, with no statistically significant differences between them (p = 0.758). Adequate urinary continence was achieved in more than 90% of patients in both groups. DISCUSSION: There are scarce recent studies comparing the combined performance of simultaneous or sequential AUS and BA in children with neuropathic bladder. The results of our study show a much lower postoperative infection rate than previously reported in the literature. It is a single-center analysis with a relatively small sample of patients although it is among the largest series published so far, and presents the longest long-term follow-up with more than 17 years of median follow-up time. CONCLUSION: Simultaneous BA and AUS placement appears safe and efficacious in children with neuropathic bladder, with shorter LOS and no differences in postoperative complications or long-term outcomes when compared to performing the two procedures sequentially at different times.

Resultados de un programa de ecocardioscopia realizada por neurólogos en el proceso integrado en red de atención al ictus en unidades de imagen cardiaca / Results of a focused cardiac ultrasound program conducted by neurologists within a stroke care network with cardiac imaging units

Introducción y objetivos Recientemente los neurólogos han comenzado a realizar ecocardioscopia para la detección de cardiopatías en pacientes con ictus isquémico, lo cual requiere un proceso previo de formación acreditada. Se diseñó un estudio prospectivo con el objetivo de analizar la incidencia de cardiopatías detectadas por ecocardioscopia en una unidad de ictus integrada en red con una Unidad de Imagen Cardiaca y el pronóstico de la detección de cardiopatía estructural a 1 año de seguimiento. Métodos Se incluyeron los casos que ingresaron por ictus isquémico o accidente isquémico transitorio en un hospital clínico universitario de 2017 a 2021 y fueron evaluados mediante ecocardioscopia. Se estudió la presencia de cardiopatía estructural y cardiopatía embolígena. Se analizaron los eventos cardiovasculares (ECV) durante el primer año de seguimiento. Resultados Se realizó ecocardioscopia a 706 pacientes. Se detectó cardiopatía estructural en el 52,1% de los casos y cardiopatía embolígena en el 31,9%. El 5,49% había sufrido ECV al año de seguimiento. La presencia de cardiopatía estructural de novo se asoció de manera independiente con una mayor probabilidad de ECV (HR=1,72; IC95%, 1,01-2,91; p=0,046). Conclusiones La ecocardioscopia dentro de un proceso integrado en red de atención al ictus con unidades de imagen cardiaca es una técnica accesible y de alta rentabilidad diagnóstica. Su uso permite actuaciones clínicas y terapéuticas directas en la prevención de nuevas embolias cerebrales y otros ECV en este grupo de pacientes. (AU)

Introduction and objectives Recently, neurologists have begun to perform focused cardiac ultrasound for the detection of a cardiac source of embolism in stroke patients, requiring them to undergo a prior accredited training process. We designed a prospective study to analyze the incidence of heart disease detected by a focused cardiac ultrasound program within a stroke care network with cardiac imaging units and to identify the outcomes of detected structural heart disease at 1 year of follow-up. Methods We included patients admitted to a university hospital for ischemic stroke or a transient ischemic attack between 2017 and 2021 who were evaluated by focused cardiac ultrasound. We studied the presence of structural heart disease and cardioembolic sources. We analyzed cardiovascular events (CVE) during the first year of follow-up. Results Focused cardiac ultrasound was performed in 706 patients. Structural heart disease was detected in 52.1% and a cardioembolic source in 31.9%. Adverse CVE occurred in 5.49% of the patients in the first year of follow-up. The presence of de novo structural heart disease was independently associated with a higher probability of adverse CVE (HR, 1.72; 95%CI, 1.01- 2.91; P=.046). Conclusions Focused cardiac ultrasound within a stroke care network with cardiac imaging units is an accessible technique with high diagnostic yield. Its use allows clinical and therapeutic actions in the prevention of stroke recurrences and other CVEs in this group of patients. (AU)

Results of a focused cardiac ultrasound program conducted by neurologists within a stroke care network with cardiac imaging units.

INTRODUCTION AND OBJECTIVES: Recently, neurologists have begun to perform focused cardiac ultrasound for the detection of a cardiac source of embolism in stroke patients, requiring them to undergo a prior accredited training process. We designed a prospective study to analyze the incidence of heart disease detected by a focused cardiac ultrasound program within a stroke care network with cardiac imaging units and to identify the outcomes of detected structural heart disease at 1 year of follow-up. METHODS: We included patients admitted to a university hospital for ischemic stroke or a transient ischemic attack between 2017 and 2021 who were evaluated by focused cardiac ultrasound. We studied the presence of structural heart disease and cardioembolic sources. We analyzed cardiovascular events (CVE) during the first year of follow-up. RESULTS: Focused cardiac ultrasound was performed in 706 patients. Structural heart disease was detected in 52.1% and a cardioembolic source in 31.9%. Adverse CVE occurred in 5.49% of the patients in the first year of follow-up. The presence of de novo structural heart disease was independently associated with a higher probability of adverse CVE (HR, 1.72; 95%CI, 1.01- 2.91; P=.046). CONCLUSIONS: Focused cardiac ultrasound within a stroke care network with cardiac imaging units is an accessible technique with high diagnostic yield. Its use allows clinical and therapeutic actions in the prevention of stroke recurrences and other CVEs in this group of patients.

Amitriptyline for post-COVID headache: effectiveness, tolerability, and response predictors.

BACKGROUND: Headache is one of the most frequently reported symptoms in post-COVID patients. The clinical phenotype of COVID-19 headache combines phenotypic features of both tension-type headache (TTH) and migraine. We aimed to assess the effectiveness, side effects and predictors of amitriptyline (AMT) response in a real-world study setting. METHODS: We performed an observational multicentric study with a retrospective cohort. All consecutive patients with confirmed COVID-19 infection who received AMT for post-COVID headache from March 2020 to May 2021 were included. Response was evaluated by the reduction in the number of headache days per month (HDM) between weeks 8 and 12, compared with the baseline. We explored which variables were associated with a higher probability of response to AMT. RESULTS: Forty-eight patients were eligible for the study, 40/48 (83.3%) females, aged 46.85 (SD: 13.59) years. Patients had history of migraine 15/48 (31.3%) or TTH 5/48 (10.4%). The mean reduction of HDM was 9.6 (SD: 10.9; 95% CI 6.5, 12.7) days. Only 2/48 (5%) of patients discontinued AMT due to poor tolerability. History of TTH (10.9, 95% CI 1.3, 20.6) and nausea (- 8.5, 95% CI - 14.6, - 2.5) were associated with AMT response. CONCLUSIONS: This study provides real-world evidence of the potential benefit of AMT in patients with post-COVID-19 headache, especially in patients with history of TTH and without concomitant nausea.

Surrogate biomarkers of outcome for wake-up ischemic stroke.

BACKGROUND: Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. METHODS: 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. RESULTS: Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p < 0.0001). Patients with wake-up IS had higher levels of inflammation biomarkers; IL-6 levels at admission (51.5 ± 15.1 vs. 27.8 ± 18.6 pg/ml; p < 0.0001), and low vitamin D levels at 24 h (5.6 ± 5.8 vs. 19.2 ± 9.4 ng/ml; p < 0.0001) are worthy of attention. In a logistic regression model adjusted for vitamin D, OR was 15.1; CI 95%: 8.6-26.3, p < 0.0001. However, we found no difference in vitamin D levels between patients with or without clinical-DWI mismatch (no: 18.95 ± 9.66; yes: 17.84 ± 11.77 ng/mL, p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895). CONCLUSIONS: Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events.

Carotid web: the challenging diagnosis of an under-recognized entity.

BACKGROUND: Determining the cause of acute ischemic stroke is crucial for patient management, particularly for preventing future stroke. In recent years, carotid web (CW), a non-atherosclerotic disorder of the carotid wall, has been found to be an underestimated source of cerebral emboli. OBJECTIVE: The present study aimed to analyze the clinical, radiological, and pathological findings, along with the treatments performed in patients with CW and ipsilateral ischemic events. METHODS: Patients with anterior circulation ischemic stroke or transient ischemic attack and ipsilateral CW were prospectively included from January 2019 to December 2021. RESULTS: Nine patients were enrolled. The median age was 55 (43-62) years, with a female-to-male ratio of 3.5:1. Of the total, seven patients (78%) consulted for recurrent ipsilateral ischemic events. Despite medical treatment, 44% of the patients experienced new episodes. Computed tomographic angiography was suggestive of CW in all cases in which it was performed. The interval between the first ischemic event and diagnosis of CW was of 13 (6-68) months. After ruling out any other possible etiology, every patient underwent carotid revascularization, one underwent stenting and eight underwent carotidectomy. No severe or long-term complications were noted. Histological studies confirmed the diagnosis of CW. There were no recurrences after carotid revascularization during a follow-up of 24 (13-35) months. CONCLUSION: Knowledge of CW and differentiating it from atheroma plaques is essential, as medical management seems to be insufficient in many cases. Revascularization, which has been shown to be safe and effective, might be the best treatment modality.

Correction: Autoacetylation of the Ralstonia solanacearum Effector PopP2 Targets a Lysine Residue Essential for RRS1-R-Mediated Immunity in Arabidopsis.

[This corrects the article DOI: 10.1371/journal.ppat.1001202.].

Artificial urinary sphincter in congenital neuropathic bladder: Very long-term outcomes.

OBJECTIVE: Artificial urinary sphincter has been used to treat urinary incontinence in children with neuropathic bladder, although there are few studies reporting very long-term results. We assess our experience over the last 27 years in the management of artificial urinary sphincter. METHODS: A retrospective study was performed in patients with neuropathic bladder in whom an artificial urinary sphincter was placed in our institution between 1994 and 2020. Demographic variables, pre- and post-artificial urinary sphincter implantation urodynamic studies, long-term outcomes, and postoperative complications were collected. RESULTS: An artificial urinary sphincter was implanted in 71 patients (median age 14.5; interquartile range 12.8-15.9), with a median follow-up time of 17.2 years (interquartile range 9.8-23.9 years). Thirty-nine patients underwent enterocystoplasty combined with artificial urinary sphincter placement and 32 underwent artificial urinary sphincter implantation alone, of whom 12 patients (16.9%) eventually required an enterocystoplasty because of unexpected bladder behavior changes, usually within 3 years of artificial urinary sphincter implantation. Adequate urinary continence was reported in 90.1% of patients, nine void their bladders spontaneously, and 62 need clean intermittent catheterization. Eighteen mechanical malfunctions occurred in 15 patients (21.1%), with an average artificial urinary sphincter working life of 15.1 ± 1.3 years. In five patients artificial urinary sphincter was removed due to infection or erosion. In 12 patients (30.8%), a continent catheterizable stoma was made (before or during the follow-up) because of problems with clean intermittent catheterization through the urethra. CONCLUSION: The very long-term results of this study demonstrate that artificial urinary sphincter is an effective treatment for urinary incontinence in neuropathic bladder patients. Long-term follow-up is important to identify potential unexpected changes in bladder behavior in these patients.

Buried penis surgical treatment in children: Dorsal dartos flap VS. Fascia fixation. A retrospective cohort study.

INTRODUCTION: Several surgical techniques for buried penis (BP) treatment have been described, although there is not a reference pattern for it. In our institution, we have traditionally performed penis fixation to Buck's fascia at 3 points. In 2014 we introduced a dorsal dartos flap technique, fixed at both sides of the penis base. OBJETIVE: To compare both techniques and their long-term outcomes. METHODS: A retrospective cohort study was conducted on consecutive patients with BP who underwent surgery between 2010 and 2018. They were divided according to surgical technique performed: group A (fascia fixation) and B (dorsal dartos flap). Demographic variables, surgical time and postoperative complications were analyzed. Long-term cosmetic outcomes were evaluated through a telephone survey to patients parents. RESULTS: Thirty-five patients were included (16 group A; 19 group B). Median age at intervention was 9.7 years in group A, with no statistical differences with group B (7.3 years; p = 0.071). No statistically significant differences were observed in mean surgical time or postoperative complications between both groups. Cosmetic outcomes (Table 2) were significantly better in group B, which presented higher percentages of satisfaction with the outcomes (95% vs. 64%; p = 0.02) and age at intervention (89% vs. 59%; p = 0.032), higher perception of the procedure as "minimally invasive" (100% vs. 71%; p = 0.013) and higher recommendation rate of the intervention (95% vs. 57%; p = 0.029). CONCLUSIONS: Dorsal dartos flap is a reproducible, minimally invasive technique with minimal adverse effects and satisfactory long-term results. It has fewer postoperative complications and more satisfactory cosmetic results compared to fascia fixation.

Creation of Tissue-Engineered Urethras for Large Urethral Defect Repair in a Rabbit Experimental Model.

Introduction: Tissue engineering is a potential source of urethral substitutes to treat severe urethral defects. Our aim was to create tissue-engineered urethras by harvesting autologous cells obtained by bladder washes and then using these cells to create a neourethra in a chronic large urethral defect in a rabbit model. Methods: A large urethral defect was first created in male New Zealand rabbits by resecting an elliptic defect (70 mm2) in the ventral penile urethra and then letting it settle down as a chronic defect for 5-6 weeks. Urothelial cells were harvested noninvasively by washing the bladder with saline and isolating urothelial cells. Neourethras were created by seeding urothelial cells on a commercially available decellularized intestinal submucosa matrix (Biodesign® Cook-Biotech®). Twenty-two rabbits were divided into three groups. Group-A (n = 2) is a control group (urethral defect unrepaired). Group-B (n = 10) and group-C (n = 10) underwent on-lay urethroplasty, with unseeded matrix (group-B) and urothelial cell-seeded matrix (group-C). Macroscopic appearance, radiology, and histology were assessed. Results: The chronic large urethral defect model was successfully created. Stratified urothelial cultures attached to the matrix were obtained. All group-A rabbits kept the urethral defect size unchanged (70 ± 2.5 mm2). All group-B rabbits presented urethroplasty dehiscence, with a median defect of 61 mm2 (range 34-70). In group-C, five presented complete correction and five almost total correction with fistula, with a median defect of 0.3 mm2 (range 0-12.5), demonstrating a significant better result (p = 7.85 × 10-5). Urethrography showed more fistulas in group-B (10/10, versus 5/10 in group-C) (p = 0.04). No strictures were found in any of the groups. Group-B histology identified the absence of ventral urethra in unrepaired areas, with squamous cell metaplasia in the edges toward the defect. In group-C repaired areas, ventral multilayer urothelium was identified with cells staining for urothelial cell marker cytokeratin-7. Conclusions: The importance of this study is that we used a chronic large urethral defect animal model and clearly found that cell-seeded transplants were superior to nonseeded. In addition, bladder washing was a feasible method for harvesting viable autologous cells in a noninvasive way. There is a place for considering tissue-engineered transplants in the surgical armamentarium for treating complex urethral defects and hypospadias cases.

Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome.

BACKGROUND AND PURPOSE: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSSbaseline - NIHSS24hours = ΔNIHSS6-24h), to examine its relevance to AIS mechanisms and long-term outcomes. METHODS: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced ΔNIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS6-24h was examined. Finally, the association of ΔNIHSS6-24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). RESULTS: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median ΔNIHSS6-24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS6-24h (R2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R2=0.27), but much of the variance remained unexplained. ΔNIHSS6-24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS3-24h was similarly associated with 90-day outcomes. CONCLUSIONS: The dynamic phenotype, ΔNIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS6-24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.