Differences in Neuropathology between Nitroglycerin-Induced Mouse Models of Episodic and Chronic Migraine.

Multiple animal models of migraine have been used to develop new therapies. Understanding the transition from episodic (EM) to chronic migraine (CM) is crucial. We established models mimicking EM and CM pain and assessed neuropathological differences. EM and CM models were induced with single NTG or multiple injections over 9 days. Mechanical hypersensitivity was assessed. Immunofluorescence utilized c-Fos, NeuN, and Iba1. Proinflammatory and anti-inflammatory markers were analyzed. Neuropeptides (CGRP, VIP, PACAP, and substance P) were assessed. Mechanical thresholds were similar. Notable neuropathological distinctions were observed in Sp5C and ACC. ACC showed increased c-Fos and NeuN expression in CM (p < 0.001) and unchanged in EM. Sp5C had higher c-Fos and NeuN expression in EM (p < 0.001). Iba1 was upregulated in Sp5C of EM and ACC of CM (p < 0.001). Proinflammatory markers were strongly expressed in Sp5C of EM and ACC of CM. CGRP expression was elevated in both regions and was higher in CM. VIP exhibited higher levels in the Sp5C of EM and ACC of CM, whereas PACAP and substance P were expressed in the Sp5C in both models. Despite similar thresholds, distinctive neuropathological differences in Sp5C and ACC between EM and CM models suggest a role in the EM to CM transformation.

Effectiveness of endovascular treatment for in-hospital stroke vs. community-onset stroke: a propensity score-matched analysis.

BACKGROUND: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment. METHODS: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis. RESULTS: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups. CONCLUSION: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients.

Effects of parental holding on pain response in young children during cystometry: A randomized controlled trial.

INTRODUCTION: Cystometry is essential for evaluating bladder function. However, children may react negatively to the physical pain of urethral catheterization or anxiety and fear of an unfamiliar environment. These pain responses during the cystometry procedure may interfere with the cystometry procedure and make it difficult to interpret the cystometry result. In this regard, the International Children's Continence Society has advised performing cystometry while holding infants as an effective nonpharmacological pain management method, but there is insufficient evidence to support this. PURPOSE: This study aimed to analyze the effect of parental holding on reducing pain in children during cystometry. METHODS: This was an experimental study in a randomized controlled pre-post test design. A total of 64 participants aged 6-18 months were recruited. During cystometry, the participants in the experimental group were placed on the parent's laps and held in the parents' arms. The participants in the control group were laid down on the examination table. During the procedure, both groups of parents were allowed to touch their children in all ways except holding them and to use the pacifier if they wished. The behavioral (face, leg, activity, cry, consolability scale) and physiological (oxygen saturation and heart rate) pain responses were measured at three-time points (immediately, 3, and 10 min after urethral catheter insertion). RESULTS: Comparing the two groups, in the experimental group, the behavioral pain response at 3 min after urethral catheter insertion (t = -2.165, p = 0.034) and 10 min after (t = -3.155, p = 0.002) was decreased compared with that immediately after urethral catheter insertion. In addition, oxygen saturation increased more (t = 2.021, p = 0.048), and the heart rate decreased more (t = -2.033, p = 0.047) at 10 min than at 3 min after urethral catheter insertion in the experimental group. CONCLUSIONS: This study revealed that parental holding could reduce pain responses during cystometry in children. Further research is required to confirm the applicability and usefulness of parental holding during cystometry.

Macrophages mobilized by the overexpression of the macrophage-colony stimulating factor promote efficient recovery of the ischemic muscle functionality.

AIMS: Narrowing or occlusion of arteries that supply the limbs can evolve to critical limb ischemia. M-CSF promotes proliferation, differentiation and survival of monocytes and macrophages, and polarization of macrophages to M2-subtype, which are essential elements for vessel formation and tissue repair. Based on these properties of M-CSF, we hypothesize that transfection of M-CSF into ischemic limbs may promote vessel formation and repair of ischemic limbs. MAIN METHODS: Hindlimb ischemia was surgically induced in 10-12 weeks old Balb/c and gene therapy was performed with intramuscular application of either uP-MCSF or uP plasmids (100 µg). Macrophage and monocyte subpopulations were assessed by flow cytometry and blood flow was monitored by Laser Doppler Perfusion Imaging (LDPI). Thirty days after transfection, we assessed gastrocnemius mass and muscle force, subsequently collecting the muscle for histology. KEY FINDINGS: We successfully developed the uP-MCSF plasmid, which increases M-CSF expression in the muscle transiently. Thirty days after uP-MCSF gene therapy in ischemic muscles, the treated group presented: improved muscle force, reduced fibrosis and increased arteriogenesis, although LDPI analysis did not show any significant difference in blood flow among groups. Noteworthy, we observed a temporary increase in MHCIIhighCD206high macrophages after uP-MCSF transfection. SIGNIFICANCE: M-CSF gene therapy improved ischemic muscle functionality by promoting arteriogenesis and decreasing fibrosis, likely through increased MHCIIhighCD206high macrophages and not via classically known M2-macrophages.

Analysis of factors affecting permanent clean intermittent catheterization and bladder function after primary neurosurgical repair of lipomyelomeningocele.

AIMS: This study was conducted to identify potential risk factors for permanent clean intermittent catheterization (CIC) and incontinence in patients with lipomyelomeningocele (LMMC) and evaluate how LMMC affects bladder function prognosis, measured by urodynamic (UD) score. METHODS: This retrospective study analyzed the electronic health records of patients who underwent primary neurosurgical repair for LMMC at a single tertiary referral center between January 2012 and December 2016 and were followed at least 3 years after surgery. Data regarding bladder function were obtained from medical records for multiple time points, including before surgery, after surgery but before hospital discharge, 3 months after surgery, and at outpatient visits during follow-up. RESULTS: This study enrolled 120 patients. At a mean follow-up of 62.6 ± 13.9 months after primary neurosurgical LMMC repair, 22 (18.3%) patients continued to require CIC for bladder emptying, only 7 (31.8%) of whom maintained bladder continence. A multivariate logistic regression model identified age at the time of surgery and the type of LMMC as significant presurgical prognostic risk factors for permanent CIC. In addition, postoperative urinary retention and a UD score greater than or equal to 5 measured 3 months after surgery were identified as significant postsurgical risk factors for permanent CIC and urinary incontinence. A linear mixed model adjusted for age at the time of surgery showed that patients with a transitional or chaotic LMMC type were more likely to experience gradual bladder function decline than patients with other LMMC types. CONCLUSIONS: This study identified both presurgical (age at the time of surgery, LMMC type) and postsurgical (postoperative urinary retention, UD score greater than or equal to 5 at 3 months postsurgery) risk factors for permanent CIC and urinary incontinence. In addition, LMMC type was identified as a prognostic risk factor for bladder function decline. These results will enhance the current understanding of bladder function outcomes in patients who undergo surgical treatment for LMMC.

Adjuvant properties of IFN-γ and GM-CSF in the scFv6.C4 DNA vaccine against CEA-expressing tumors.

Tumor-associated carcinoembryonic antigen (CEA) is a natural target for vaccines against colorectal cancers. Our previous experience with a DNA vaccine with scFv6.C4, a CEA surrogate, showed a CEA-specific immune response with 40% of tumor-free mice after challenge with B16F10-CEA and 47% with MC38-CEA cells. These percentages increased to 63% after using FrC as an adjuvant. To further enhance the vaccine efficacy, we tested GM-CSF and IFNγ as adjuvants. C57BL/6J-CEA2682 mice were immunized 4 times with uP-PS/scFv6.C4, uP-PS/scFv6.C4 + uP-IFNγ, or uP-PS/scFv6.C4 + uP-GMCSF. After one week, the mice were challenged with MC38-CEA, and tumor growth was monitored over 100 days. Immunization with scFv6.C4 and scFv6.C4 + GM-CSF resulted in a gradual increase in the anti-CEA antibody titer, while scFv6.C4 + IFNγ immunization led to a rapid and sustained increase in the titer. The addition of IFNγ also induced higher CD4 + and CD8 + responses. When challenged, almost 80% of the scFv6.C4 + IFNγ-vaccinated mice did not develop tumors, while the others had a significant tumor growth delay. The probability of being tumor-free was 2700% higher using scFv6.C4 + IFNγ than scFv6.C4. The addition of GM-CSF had no additional effect on tumor protection. DNA immunization with scFv6.C4 + IFNγ, but not GM-CSF, increased the antitumor effect via readily sustained specific humoral and cytotoxic responses to CEA.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Trends in hydrogel-based encapsulation technologies for advanced cell therapies applied to limb ischemia.

Ischemia occurs when blood flow is reduced or restricted, leading to a lack of oxygen and nutrient supply and removal of metabolites in a body part. Critical limb ischemia (CLI) is a severe clinical manifestation of peripheral arterial disease. Atherosclerosis serves as the main cause of CLI, which arises from the deposition of lipids in the artery wall, forming atheroma and causing inflammation. Although several therapies exist for the treatment of CLI, pharmacotherapy still has low efficacy, and vascular surgery often cannot be performed due to the pathophysiological heterogeneity of each patient. Gene and cell therapies have emerged as alternative treatments for the treatment of CLI by promoting angiogenesis. However, the delivery of autologous, heterologous or genetically modified cells into the ischemic tissue remains challenging, as these cells can die at the injection site and/or leak into other tissues. The encapsulation of these cells within hydrogels for local delivery is probably one of the promising options today. Hydrogels, three-dimensional (3D) cross-linked polymer networks, enable manipulation of physical and chemical properties to mimic the extracellular matrix. Thus, specific biostructures can be developed by adjusting prepolymer properties and encapsulation process variables, such as viscosity and flow rate of fluids, depending on the final biomedical application. Electrostatic droplet extrusion, micromolding, microfluidics, and 3D printing have been the most commonly used technologies for cell encapsulation due to their versatility in producing different hydrogel-based systems (e.g., microgels, fibers, vascularized architectures and perfusable single vessels) with great potential to treat ischemic diseases. This review discusses the cell encapsulation technologies associated with hydrogels which are currently used for advanced therapies applied to limb ischemia, describing their principles, advantages, disadvantages, potentials, and innovative therapeutic ideas.

Long-term usage pattern and satisfaction survey of continent catheterizable channels.

INTRODUCTION: We investigated the long-term usage pattern and satisfaction of continent catheterizable channels (CCCs). METHODS: From 2005 to 2018, CCCs, including Mitrofanoff and antegrade continent enema (ACE) channels, were made in 67 patients (Mitrofanoff in 21 patients, ACE channels in 43 patients, and both in three patients) in our institution. An online survey was conducted for these patients in order to assess usage pattern, continent status, difficulty in usage, and patient satisfaction. RESULTS: Sixteen (66.7%) out of 24 patients with the Mitrofanoff channel and 39 (84.7%) out of 46 patients with the ACE channel completed the online survey. In the Mitrofanoff channel group, 10 (62.5%) patients had spina bifida, two (12.5%) had Hinman syndrome, one (6.3%) had posterior urethral valves, and three (18.8%) had urethral trauma or atresia. Additionally, the mean age of the patients at the time of surgery was 10.0 years, and the median follow-up duration was 10.9 years. All patients were using the Mitrofanoff channel to perform clean intermittent catheterization (CIC). Eleven patients (68.8%) had difficulty with catheterization, mostly at the stomal site. Most patients conducted CIC more than four times a day (13, 81.3%). Regarding urination status, seven patients (43.8%) responded that they were satisfied and nine (56.2%) responded they were neutral. In the ACE channel group, 35 patients (89.7%) had spina bifida, seven (17.9%) had cloacal anomalies, and 26 (66.7%) had anorectal malformations. The mean age of the patients at the time of surgery was 8.4 years, and the median follow-up period was 7.4 years. Two (5.1%) patients were no longer using their ACE channels, but 15 (38.5%) patients were still using their channels almost daily. Twenty-eight (71.8%) patients complained that performing enema was time-consuming, and seven (17.9%) patients reported pain when performing ACE and fecal incontinence. Most patients were satisfied with their defecation status (23, 59%), 15 (38.5%) were neutral, and one (2.6%) was dissatisfied. CONCLUSIONS: While most patients who had either Mitrofanoff or ACE channels were still using their channels effectively, approximately half of the patients with CCCs demonstrated neutral satisfaction with their current status; this shows a poor result compared to previous reports. Considering the results of our patient-based study, thorough explanations should be provided to patients who are candidates for Mitrofanoff and ACE procedures; additionally, the discomfort related to the procedures should be comprehensively assessed during follow-up consults.

Comparison of intraoperative and short-term postoperative outcomes between robot-assisted laparoscopic multi-port pyeloplasty using the da Vinci Si system and single-port pyeloplasty using the da Vinci SP system in children.

PURPOSE: We compared the intraoperative and postoperative outcomes of single-port robot-assisted laparoscopic pyeloplasty (S-RALP) using the da Vinci SP® system and conventional multi-port robot-assisted laparoscopic pyeloplasty (M-RALP) in pediatric patients. MATERIALS AND METHODS: Multi-port and single-port pyeloplasty have been performed in pediatric patients in our institution since October 2015 and February 2019, respectively. We conducted an entire cohort comparison. Considering the learning curve of M-RALP, we defined the last 15 cases of M-RALP as a subgroup of M-RALP and compared this subgroup with the entire cohort of S-RALP patients. RESULTS: Thirty-one patients who underwent multi-port pyeloplasty and 15 patients who underwent single-port pyeloplasty were enrolled in this study. Age, height, body weight, laterality, surgical indication, and ipsilateral differential renal function were statistically similar in the M-RALP and S-RALP groups. The median operative time (3.0 h vs. 2.4 h; p=0.01) and the median console time (2.2 h vs. 1.5 h; p<0.001) were longer in the M-RALP group than in the S-RALP group. There was no significant difference in operative time or console time between the M-RALP subgroup and the S-RALP group. There were no significant differences in the length of hospitalization, pain score, morphine-equivalent use of analgesics, or postoperative differential renal function in all comparisons. CONCLUSIONS: This study confirmed that pyeloplasty using the da Vinci® SP system can be started by robotic surgeons who can overcome the learning curve. Robot-assisted laparoscopic single-port pyeloplasty is feasible in noninfant pediatric patients.

Comparison between prepubertal and postpubertal patients with obstructed hemivagina and ipsilateral renal anomaly syndrome.

BACKGROUND: Obstructive hemivagina with ipsilateral renal anomaly (OHVIRA) syndrome is a rare, complex congenital anomaly with an unknown prevalence. However, case reports and small studies on OHVIRA syndrome have increased rapidly in the last 20 years, which may be related to increased use of imaging, surgical techniques, and prenatal sonography. OBJECTIVE: This study aimed to analyze and compare patients with OHVIRA syndrome diagnosed in the prepubertal and postpubertal periods to understand the disease characteristics and improve clinical management. STUDY DESIGN: A retrospective cohort study was conducted including 65 patients with OHVIRA syndrome who were diagnosed between January 2004 and September 2018 at a tertiary university hospital. RESULTS: Among the 65 patients, 44 patients were diagnosed with OHVIRA syndrome during the prepubertal period and 21 patients were diagnosed postpubertally. Compared with postpubertally diagnosed patients with OHVIRA syndrome, those diagnosed prepubertally were mostly asymptomatic at initial presentation (82% versus [vs.] 0%, P < 0.001), had a higher incidence of ectopic ureter (68% vs. 24%, P = 0.001), and presented with a higher incidence of multicystic dysplastic kidney (61% vs. 19%, P = 0.01). Approximately half of the patients with prepubertal OHVIRA syndrome (53%) showed spontaneous resolution of hemivaginal fluid within 5 years. Among the patients with postpubertally diagnosed OHVIRA syndrome, those in the pain-dominant group had a larger amount of hemivaginal fluid than those in the painless discharge-dominant group (54% vs. 10%, P = 0.036). Superimposed infection of hemivaginal fluid was markedly present in the discharge-dominant group (9% vs. 75%, P = 0.006). CONCLUSIONS: Clinical characteristics of patients with OHVIRA syndrome are altered based on the time of initial diagnosis. Follow-up and timely intervention should be proceeded accordingly.

Immediate and Long-Term Outcomes of Reperfusion Therapy in Patients With Cancer.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528­6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

A retrospective analysis of ureteropelvic junction obstructions in patients with horseshoe kidney.

BACKGROUND: Ureteropelvic junction obstruction (UPJO) is often encountered in patients with a horseshoe kidney (HSK) and may require surgical intervention. This study retrospectively investigated obstruction causes in HSK patients with UPJOs to determine the most suitable surgical method. METHODS: Twenty HSK patients with UPJO who underwent pyeloplasty between July 2000 and June 2020 and were followed-up for more than six months in our institution were included in the study. The clinical characteristics, obstruction causes, and surgical outcomes were analyzed. RESULTS: The median age at the time of the operation was 4.1 years [interquartile range (IQR): 1.8-10.6]. Hydronephrosis (HN) was found prenatally in 5 patients (25.0%). Pyeloplasty was performed by open, laparoscopic, and robotic techniques in 6, 10, and 4 patients, respectively. Sixteen patients (80.0%) had high ureteral insertion. Twelve patients (60.0%) had crossing vessels, and eight had a high ureteral insertion and crossing vessels. The median follow-up duration was 4.0 years (IQR: 1.8-8.9); no patient required additional surgery. The median differential renal function was 38.0% (IQR: 16.9-43.0%) preoperatively and 38.0% (IQR: 13.3-48.2%) postoperatively. CONCLUSIONS: UPJOs in HSKs were primarily caused by a high ureteral insertion and crossing vessels. Dismembered pyeloplasty was successfully performed in all surgical modalities such as the open, laparoscopic, and robotic approaches. Attention must be given to patients with HSKs, even in those without HN, to avoid UPJO development.

Renal growth slope in children with congenital and acquired solitary functioning kidneys.

PURPOSE: This study aimed to analyze the renal growth slope in children with congenital and acquired solitary functioning kidneys. METHODS: This retrospective study included all renal ultrasonography examinations performed in children in the agenesis, multicystic dysplastic kidney (MCDK), or nephrectomy group between September 2002 and February 2019. We reviewed the images and recorded the contralateral kidney size only when there was no focal lesion. Linear mixed model or piecewise linear mixed model analyses with a time point of 24 months of age were performed. RESULTS: There were 132 patients, including 26 patients in the agenesis group, 35 in the MCDK group, and 71 in the nephrectomy group. The nephrectomy group showed the largest baseline kidney size (7.4 cm vs. 5.3 cm in the agenesis group [P<0.001] and 5.2 cm in the MCDK group [P<0.001]) and the smallest overall growth slope (0.04 cm/mo vs. 0.06 cm/mo in the agenesis group [P=0.004] and 0.07 cm/mo in the MCDK group [P<0.001]). However, considering the time point of 24 months for reaching adult renal function, there were significant changes in slope, from 0.1 cm/mo before 24 months of age to 0.03 cm/mo after 24 months of age in all three groups (P<0.001), without a significant difference among the groups. CONCLUSION: Significant changes were found in the renal growth slope before and after 24 months of age, with no significant difference between congenital and acquired solitary functioning kidneys.

Skeletal muscle healing by M1-like macrophages produced by transient expression of exogenous GM-CSF.

BACKGROUND: After traumatic skeletal muscle injury, muscle healing is often incomplete and produces extensive fibrosis. The sequence of M1 and M2 macrophage accumulation and the duration of each subtype in the injured area may help to direct the relative extent of fibrogenesis and myogenesis during healing. We hypothesized that increasing the number of M1 macrophages early after traumatic muscle injury would produce more cellular and molecular substrates for myogenesis and fewer substrates for fibrosis, leading to better muscle healing. METHODS: To test this hypothesis, we transfected skeletal muscle with a plasmid vector to transiently express GM-CSF shortly after injury to drive the polarization of macrophages towards the M1 subset. C57BL/6 mouse tibialis anterior (TA) muscles were injured by contusion and electroporated with uP-mGM, which is a plasmid vector that transiently expresses GM-CSF. Myogenesis, angiogenesis, and fibrosis were evaluated by histology, immunohistochemistry, and RT-qPCR; subpopulations of macrophages by flow cytometry; and muscle functioning by the maximum running speed on the treadmill and the recovery of muscle mass. RESULTS: Muscle injury increased the number of local M1-like macrophages and decreased the number of M2-like macrophages on day 4, and uP-mGM treatment enhanced this variation. uP-mGM treatment decreased TGF-ß1 protein expression on day 4, and the Sirius Red-positive area decreased from 35.93 ± 15.45% (no treatment) to 2.9% ± 6.5% (p < 0.01) on day 30. uP-mGM electroporation also increased Hgf, Hif1α, and Mtor gene expression; arteriole density; and muscle fiber number during regeneration. The improvement in the quality of the muscle tissue after treatment with uP-mGM affected the increase in the TA muscle mass and the maximum running speed on a treadmill. CONCLUSION: Collectively, our data show that increasing the number of M1-like macrophages immediately after traumatic muscle injury promotes muscle recovery with less fibrosis, and this can be achieved by the transient expression of GM-CSF.

Buccal Mucosa Tube Graft for Failed Hypospadias Repair: Worth it or Not?

OBJECTIVE: To report the outcome of buccal mucosa tube graft (BMTG) over time in correcting failed hypospadias. METHODS: We conducted a retrospective analysis, reviewing charts of all 69 patients who underwent BMTG to repair hypospadias between January 2005 and October 2016. Twenty-one patients were excluded, leaving 48 eligible study subjects. In patients with penile curvatures, corrective procedures (including urethral division, corporoplasty, and local skin flap) took place prior to grafting. RESULTS: Mean age at surgery was 8.96 years, and mean duration of follow-up was 73.10 ± 30.31 months. A mean of 1.88 previous surgeries was recorded. During follow-up, only 7 patients (14.5%) were complication free. The other 41 patients required at least 1 additional procedure. Stricture-free rates were 50%, 35.4%, and 27% at 1, 3, and 12 months after BMTG, respectively. Among 37 patients with postoperative stricture, 25 were treated only by endoscopic procedures. Single operation prior to BMTG (P= .004) and usage of larger catheter size (>8Fr) (P = .029) were confirmed significant factors associated with better stricture-free survival after BMTG by log-rank test. After several additional procedures, 46 patients (95.8%) reported normal urination with mean maximal urinary flow of 9.55 mL/s and post-void residual of 16.08 mL for at least 12 months on last visit. CONCLUSION: BMTG after failed hypospadias repair seems prone to complications, primarily urethral stricture. However, a large number of patients with postoperative stricture could be treated simply by endoscopic procedures. Given the better results of staged approach, BMTG should be only applied to highly selected patients with failed hypospadias.

Urethral duplication in male children: A study of 12 cases.

PURPOSE: To present our experience in urethral duplication focusing on detailed surgical management. METHODS: We retrospectively reviewed the records of 12 male patients treated for urethral duplication between 2005 and 2017. Evaluations included ultrasound, retrograde urethrography, cystoscopy, and voiding cystourethrography. RESULTS: The age at presentation ranged from birth to 11 years. All 12 cases were classified using the Effmann classification. Case 1-4 patients with type I underwent excision of the dorsal accessory urethra by stripping technique. In case 5 patient(type IA) with two adjacent apical urethras, the septum was opened to form a single channel. Case 6 patient with type IB underwent visual internal urethrotomy near bulbous urethra to combine urethra into one channel. Five patients classified as type II (one with a type IIA1, and four with type IIA2 urethras). Urethral duplication was incidentally found during epispadias repair in case 7 patient with type IIA1, which was corrected by ventral plication, and excision of the dorsal epispadial urethra with stripping technique just below pubic bone. Case 8 patient with type IIA2 also required dorsal urethral excision with stripping technique. The two Y-type patients (case 10, 11) underwent urethrourethrostomy with a single-stage buccal mucosa tube graft, followed by repetitive surgeries owing to urethral stricture. One type III patient presented with penile inflammation and suprapubic pain, and underwent excision of both the dorsal urethra and nonfunctional anterior bladder. CONCLUSIONS: Urethral duplication requires individualized surgical approaches based on the anatomical and functional characteristics. Because prognosis is variable depending on type and accompanied anomalies, these should be taken into account when planning a comprehensive workup and surgical management. LEVEL OF EVIDENCE: Level IV.

Effects of 1% Lidocaine Instillation on Overactive Bladder Induced by Bladder Outlet Obstruction in Rats.

PURPOSE: Lidocaine is a common local anesthetic and antiarrhythmic drug that acts via the local anesthetic effect of blocking voltage-gated sodium channels in peripheral neurons. To evaluate lidocaine as a therapeutic agent, we investigated optimal concentrations and effects of intravesical lidocaine instillation in a bladder outlet obstruction (BOO)-induced rat model of overactive bladder (OAB). MATERIALS AND METHODS: To determine the therapeutic dosage of lidocaine, 16 female Sprague-Dawley (SD) rats (mean weight = 200 ± 20 g) were divided into four treatment groups: those receiving saline, 0.5% lidocaine, 1% lidocaine, and 2% lidocaine (n = 4 per group). Twenty-four additional SD rats were divided into two groups to investigate the effect of 1% lidocaine treatment in rats with BOO and normal rats (n = 12 per group). Cystometry was performed by infusing physiological saline and lidocaine into the bladder at a slow infusion rate (0.04 mL/min). Cystometric parameters were analyzed using PowerLab®. The expression of c-Fos, a protein expressed by C-fibers in the spinal cord (L6), was investigated via western blotting. RESULTS: Among the test lidocaine doses, only 1% lidocaine increased the intercontraction interval (ICI) (control mean = 500.56 ± 24.4 s; treatment mean = 641.0 ± 49.3 s; p < .01) without changes in threshold pressure and basal pressure. In the BOO-induced OAB group, the ICI increased significantly after instillation of 1% lidocaine (control mean = 135.8 ± 12.87 s; OAB-group mean = 274.2 ± 33.21 s; p < .01). Detrusor overactivity and non-voiding contraction were observed in the control group but not in rats with BOO after lidocaine instillation. The expression of c-Fos in C-fibers in the spinal cord (L6) decreased significantly after 1% lidocaine treatment in rats with BOO. CONCLUSION: Intravesical instillation of 1% lidocaine improves cystometric parameters without deterioration of contractility by blocking excessive C-fiber activity in the rat model of BOO-induced OAB. Therefore, instillation of 1% lidocaine has minimal effects on normal nerves while blocking nerves that contribute to OAB. Our findings suggest that intravesical instillation of 1% lidocaine is a useful treatment for OAB.

Robot-assisted laparoscopic single-port pyeloplasty using the da Vinci SP® system: initial experience with a pediatric patient.

INTRODUCTION: The da Vinci SP® Robotic Surgical Platform (Intuitive Surgical) was recently introduced to overcome triangulation and motion restriction during laparoendoscopic single-site surgery. The authors describe a pure, single-site, robot-assisted, laparoscopic pyeloplasty (RALP) using the da Vinci SP System in a pediatric patient. MATERIAL AND METHODS: A 10-year-old patient with ureteropelvic junction obstruction underwent pyeloplasty conducted using the da Vinci SP® System. Retrospective perioperative and immediate postoperative outcomes were investigated. RESULTS: Surgery was completed with pure single-site surgery without additional port placement or standard multiport conversion. The total operation time was 211 min, and the console time was 90 min. The docking time was much greater than that of previous pyeloplasty operations using multiport system. This result may be because of difficulties caused by bulky instrumentation entering the pneumoperitoneum. The estimated blood loss was minor, and there were no intraoperative or perioperative complications. Ureteral stent was removed after 4 weeks. Cosmetic outcomes were satisfactory. CONCLUSIONS: Pure, single-site RALP using da Vinci SP® System seems feasible in aging children. Additional studies involving more patients, younger children, and long-term outcomes are required.