Relative anemia and perioperative stroke in children with moyamoya.

OBJECTIVES: Surgical revascularization for moyamoya arteriopathy decreases long-term stroke risk but carries a risk of perioperative ischemic complications. We aimed to evaluate modifiable stroke risk factors in children undergoing surgical revascularization for moyamoya. MATERIALS AND METHODS: In this exploratory, single-center, retrospective cohort study, medical records of pediatric patients undergoing surgical revascularization for moyamoya arteriopathy at our center between 2003 and 2021 were reviewed. Candidate modifiable risk factors were analyzed for association with perioperative stroke, defined as ischemic stroke ≤7 days after surgery. RESULTS: We analyzed 53 surgeries, consisting of 39 individual patients undergoing indirect surgical revascularization of 74 hemispheres. Perioperative ischemic stroke occurred following five surgeries (9.4%). There were no instances of hemorrhagic stroke. Larger pre-to-postoperative decreases in hemoglobin (OR 3.90, p=0.017), hematocrit (OR 1.69, p=0.012) and blood urea nitrogen (OR 1.83, p=0.010) were associated with increased risk of perioperative ischemic stroke. Weight-adjusted intraoperative blood loss was not associated with risk of perioperative ischemic stroke (OR 0.94, p=0.796). Among children with sickle cell disease, all of whom underwent exchange transfusion within one week prior to surgery, none experienced perioperative stroke. CONCLUSIONS: Decreases in hemoglobin, hematocrit, and blood urea nitrogen between the preoperative and postoperative periods are associated with increased risk of perioperative stroke. These novel findings suggest that dilutional anemia, possibly due to standardly administered hyperhydration, may increase the risk of perioperative stroke in some children with moyamoya. Further work optimizing both mean arterial pressure and oxygen-carrying capacity in these patients, including consideration of alternative blood transfusion thresholds, is necessary.

Anterior Ear Reconstruction with the Posterior Pull-through Flap.

Background: Defects of the central ear after skin cancer removal remain a common problem for the reconstructive surgeon. The experience with a one-stage, postauricular, skin-island flap passed through the cartilage to reconstruct ear defects is reported. Methods: Patients with an intact ear helix and an anterior full-thickness defect (cartilage defects included) were reconstructed with a skin-island flap based on posterior subcutaneous tissue deep to the flap base. The flap was passed through a generous aperture created in the ear cartilage. The skin at the base was incised superficially after the flap was passed through the cartilage to create a skin-island and avoid burial of epithelium. The flap periphery and postauricular harvest site were sutured with absorbable chromic sutures. Results: Twenty-two patients (six women, 16 men) with ear defects underwent single-stage reconstruction over a 9-year period. The defects reconstructed measured in diameter from 2 cm to 4.5 cm. Six patients required a second skin flap from the preauricular area to close ear canal defects. The pull-through flap added structural support, and prevented ear distortion. No flap necrosis occurred. Venous congestion was common and self-limiting. No epithelial cysts developed. Conclusions: A one-stage postauricular skin-island flap can reliably reconstruct anterior ear defects without distorting shape or position of the ear. Care is needed to provide a generous aperture through the ear cartilage to accommodate the flap. Healing proceeds predictably, and minimal complications are associated with this posteriorly-based, pass-through, skin-island flap in ear reconstruction.

Lip-Shortening Surgery.

BACKGROUND: Many changes are associated with the aging face. Upper lip lengthening with atrophy, lip thinning, and diminution of the lip margin are commonly seen. METHODS: Lip-shortening surgery over a 32-year period by a single surgeon is reviewed. A direct surgical excision of the upper lip skin at the base of the nose with an irregular or curvilinear incision was used. RESULTS: Facial aesthetics were improved with this direct surgical approach. A more youthful vermilion border and an increased lip projection were achieved. Lip asymmetry and an improvement in lip dynamics were also observed. A high rate of revision surgery (approximately 25%) was found in this series. The highly visible, delicate, central facial landmarks involved in lip shortening magnify small scar irregularities, and revision, although relatively minor, is often necessary. Patient satisfaction is high, as a subjective improvement in lip aesthetics is readily appreciated. Patients frequently request further shortening. CONCLUSIONS: Surgeons need to review the exigent nature of this surgery with their patients and be willing to perform the associated revisions inherent in the procedure. Lip-shortening surgery reliably improves facial aesthetics and should be used by plastic surgeons when treating the aging face.

Are weight or age limits for pediatric laparoscopic pyeloplasty? Results of a multicentric study.

INTRODUCTION: Anderson-Hynes pyeloplasty is the technique of choice for the treatment of pyeloureteral junction obstruction (PUJO) with an excellent success rate. Minimally invasive surgery has become the standard of care for the management of PUJO in children. Although it has been comparable to the open approach at all levels, its diffusion or employment in younger children has not been widely adopted. Our aim is to evaluate laparoscopic pyeloplasty outcomes from international academic centers in children under 1 year of age, focusing on feasibility and outcomes including possible complications. MATERIALS AND METHODS: This is review of consecutive infants under 1 year of age who underwent laparoscopic pyeloplasty between 2009 and 2018 with more than 12 months of follow-up. Seven different training centers with different backgrounds participated in this study. Evaluation was carried out with ultrasound and renogram before and after surgery. Demographic data, perioperative characteristics, complications, and results are described and analyzed. RESULTS: Over 9 years, 124 transperitoneal laparoscopic Anderson-Hynes pyeloplasties were performed on 123 children under 1 year of age; 88 males and 35 females, with 1 case of bilateral PUJO. Of the 124 renal units, 86 were left-sided. Mean age at surgery was 6.6 months (1 week-12 months), with 56% (n = 70) done before 6 months of age. Mean weight at surgery was 6.8 kg (3-12 kg), with 59% (n = 73) weighing less than 8 kg. Mean operative time (skin-to-skin) was 150 min (75-330 min). After a mean follow-up of 46 months (12-84 months), 12 (9%) patients developed complications, with only 1 needing a redo pyeloplasty also done laparoscopically. One child, with deterioration in renal function, underwent nephrectomy. CONCLUSION: Laparoscopic pyeloplasty under 1 year of age and/or less than 12 kilos is feasible with lower complication rate. Furthermore, age younger than 6 months and weight less than 8 kg are no longer limiting factors for a successful pyeloplasty as shown by this multicentre study.

Unique Evaluation and Management Considerations for Adolescents with Late Gynecologic and Colorectal Issues in the Setting of Anorectal Malformations.

STUDY OBJECTIVE: There is little guidance for managing pubertally identified Mullerian anomalies in patients with anorectal malformations (ARMs). We sought to assess these unique issues. DESIGN: Retrospective review SETTING: Single-institution study PARTICIPANTS: Natal female patients aged 10-25, with an ARM, cloaca, or exstrophy, who presented from 2009 to 2019 with a gynecologic concern were included. INTERVENTION: Data collection was performed and included the presenting problem, psychological evaluation, fertility and sexuality concerns, and management strategies for these problems. MAIN OUTCOME MEASURES: The main outcome was unique needs that had to be addressed in the young adult population and the type of colorectal and gynecological procedures needed on representation. RESULTS: Twelve patients were identified; all had gynecologic concerns. Ten had ARMs, including cloaca (n = 3) and cloacal exstrophy (n = 5). Median age at representation was 14.6 years (IQR = 12.7, 15.3). Colorectal revisions included posterior sagittal anorectoplasty (n = 1), resection of bowel attached to urogenital sinus (n = 1), and appendicostomy revision (n = 1). Gynecologic issues included dysmenorrhea (n = 8), obstructed Mullerian anomaly (n = 6), and introital stenosis (n = 5). Behavioral health concerns (n = 9) and fertility/sexuality concerns (n = 4) were identified. Median time from first visit to reconstruction was 1.5 years (IQR = 0.5, 1.5), providing multiple visits to achieve consensus among patients and providers before intervention, including vaginal or introital repair (n = 5) and hysterectomy of obstructed uterine horns (n = 3). CONCLUSIONS: Goal-directed follow-up is required before surgical management to identify psychological and reproductive issues in patients with ARMs who have gynecologic concerns. Patient input and psychologic consultation are helpful for patients requiring staged reconstruction.

Latitudes and attitudes: A multinational study of laparoscopic pyeloplasty in children.

PURPOSE: The Anderson-Hynes technique has been the treatment of choice for primary ureteropelvic junction obstruction in children. Laparoscopic approach has shown similar outcomes to open, with advantages of shorter hospital stay and less pain. We reviewed the experience of 11 geographically diverse, tertiary pediatric urology institutions focusing on the outcomes and complications of laparoscopic pyeloplasty. MATERIALS AND METHODS: A descriptive, retrospective study was conducted evaluating patients undergoing Anderson-Hynes dismembered laparoscopic pyeloplasty. Centers from four different continents participated. Demographic data, perioperative management, results, and complications are described. RESULTS: Over a 9-year period, 744 laparoscopic pyeloplasties were performed in 743 patients. Mean follow-up was 31 months (6-120m). Mean age at surgery was 82 months (1 w-19 y). Median operative time was 177 min. An internal stent was placed in 648 patients (87%). A catheter was placed for bladder drainage in 702 patients (94%). Conversion to open pyeloplasty was necessary in seven patients. Average length of hospital stay was 2.8 days. Mean time of analgesic requirement was 3.2 days. Complications, according to Clavien-Dindo classification, were observed in 56 patients (7.5%); 10 (1%) were Clavien-Dindo IIIb. Treatment failure occurred in 35 cases with 30 requiring redo pyeloplasty (4%) and 5 cases requiring nephrectomy (0.6%). CONCLUSION: We have described the laparoscopic pyeloplasty experience of institutions with diverse cultural and economic backgrounds. They had very similar outcomes, in agreement with previously published data. Based on these findings, we conclude that laparoscopic pyeloplasty is safe and successful in diverse geographics areas of the world.

Risk Factors and Imaging Biomarkers Associated With Perioperative Stroke in Pediatric Moyamoya Arteriopathy.

Patients with moyamoya arteriopathy are at high risk for developing ischemic stroke in the perioperative period. We sought to evaluate whether preoperative clinical and neuroimaging biomarkers are associated with postoperative stroke and transient ischemic attack in children with moyamoya following revascularization surgery. We performed a retrospective chart review of pediatric patients who underwent revascularization surgery for moyamoya in the last 15 years. Fifty-three patients who underwent 69 surgeries met the inclusion criteria. We recorded clinical predictors of stroke or transient ischemic attack within 7 days following surgery. We used Suzuki stage and Composite Cerebrovascular Stenosis Score to analyze neuroimaging. Significant risk factors for developing postoperative stroke or transient ischemic attack were younger age at surgery (P = .004) and transient ischemic attack less than 1 month prior to surgery (P < .001). Children under 5 and those with recent preoperative ischemic events should be the focus of investigation to evaluate modifiable risk factors and targeted interventions.

Oligomerization, trans-reduction, and instability of mutant NOTCH3 in inherited vascular dementia.

Cerebral small vessel disease (SVD) is a prevalent disease of aging and a major contributor to stroke and dementia. The most commonly inherited SVD, CADASIL, is caused by dominantly acting cysteine-altering mutations in NOTCH3. These mutations change the number of cysteines from an even to an odd number, but the impact of these alterations on NOTCH3 protein structure remain unclear. Here, we prepared wildtype and four mutant recombinant NOTCH3 protein fragments to analyze the impact of CADASIL mutations on oligomerization, thiol status, and protein stability. Using gel electrophoresis, tandem MS/MS, and collision-induced unfolding, we find that NOTCH3 mutant proteins feature increased amounts of inappropriate disulfide bridges, reduced cysteines, and structural instability. Presence of a second protein factor, an N-terminal fragment of NOTCH3 (NTF), is capable of further altering disulfide statuses of both wildtype and mutant proteins, leading to increased numbers of reduced cysteines and further destabilization of NOTCH3 structure. In sum, these studies identify specific cysteine residues alterations and quaternary structure induced by CADASIL mutations in NOTCH3; further, we validate that reductive factors alter the structure and stability of this small vessel disease protein.

Single institution review of Mini-ACE® low-profile appendicostomy button for antegrade continence enema administration.

PURPOSE: Malone antegrade continence enemas (MACE) provide a conduit in which the patient can achieve improved continence, be clean of stool, and gain independence in maintaining bowel function. The Mini-ACE® is a low-profile balloon button that is used to facilitate the administration of antegrade enemas. We sought to describe our practice and short-term outcomes. METHODS: This work is a retrospective review of the Mini-ACE® appendicostomy button from April 2019 to March 2021, with follow-up concluding in October 2021. Patient demographics, colorectal diagnoses, and outcomes were examined. RESULTS: Forty-three patients underwent Mini-ACE® placement; 22 (51%) were male. The average age at Mini-ACE® insertion was 9.2 years (range 3-20 years). The most common diagnoses were functional constipation in 19 (44%), anorectal malformation in 15 (35%), and Hirschsprung disease in 3 (7%), spinal differences 3 (7%). There were no intra-operative complications, but 5 (12%) required prolapse resection. The median length of stay was two days (IQR 1, 4). Patients achieved self-catheterization at 4.5 [3,7] months from MACE creation, with 38 children (88%) reporting excellent success in remaining clean of stool. CONCLUSION: The Mini-ACE® appears to be a safe and low-profile option for antegrade continence enema access. Further research is needed directly comparing complications and patient satisfaction rates between different MACE devices and overall quality of life. LEVEL OF EVIDENCE: Level IV.

Adolescent Varicocelectomy: Success at What Cost? Clinical Outcome and Cost Comparison of Surgical Ligation and Percutaneous Embolization.

Objectives: Evaluate clinical outcome, recurrence, morbidity, and cost associated with laparoscopic surgical ligation versus percutaneous embolization of adolescent varicocele. We hypothesize that both approaches are similar in outcomes, complications, and cost. Materials and Methods: A retrospective review of 56 consecutive adolescent males, ≤18 years from 2006 to 2016 with clinical varicocele who underwent laparoscopic surgical ligation or percutaneous embolization. Patient demographics, operative time, postoperative complications, success, varicocele grade, recurrence, and hospital charges were abstracted. Results: Mean age was 14.2 ± 2.1 years; 48 (86%) patients having undergone laparoscopic surgical ligation and 8 (14%) percutaneous embolization. Intervention in 45 (80%) patients was for testicular hypotrophy (mean 27.4% ± 15.6%) and 11 (20%) for pain symptomology. Median follow-up was 17.5 months (range 1-65 months). After ligation, 2 (4%) patients developed hydroceles (1 with subsequent hydrocelectomy) and 6 (12%) varicocele recurrence. There were no cases of hydrocele or varicocele recurrence after percutaneous embolization. Twenty ligation patients had postoperative scrotal ultrasound demonstrating an increase in testicular volume by a reduction in difference in testicular volume from 27.3% ± 14.7% preoperatively to 11.2% ± 13.6% postoperatively (P < .001). There was significant difference in mean operative time between the groups (surgical ligation 41.3 minutes versus percutaneous embolization 117.9 minutes, P < .001) and hospital charges for the procedure (surgical ligation $3983 versus percutaneous embolization $18.165, P < .001). Conclusions: Contrary to our hypothesis, percutaneous embolization has seemingly lower rates of postoperative hydrocele and varicocele recurrence in comparison to surgical ligation but with three times the exposure to general anesthesia and at four times the price.

Clinical Presentation and Stroke Incidence Differ by Moyamoya Etiology.

INTRODUCTION: Moyamoya arteriopathy, which can be idiopathic or associated with sickle cell disease, neurofibromatosis, Down syndrome, or cranial radiation therapy, is a progressive cerebral arteriopathy associated with high rates of incident and recurrent stroke. Little is known about how these subgroups differ with respect to clinical presentation, radiographic findings, stroke risk, and functional outcomes. METHODS: Using ICD codes, we identified children ages 28 days to 18 years treated for moyamoya arteriopathy at our tertiary care center between 2003 and 2019. Demographic, clinical, and radiographic data were extracted from the medical record. The Pediatric Stroke Recurrence and Recovery Questionnaire was administered to consenting participants. RESULTS: Sixty-nine patients met inclusion criteria (33 idiopathic, 18 sickle cell disease, 11 neurofibromatosis, 6 Down syndrome, 1 cranial radiation therapy). Median follow-up time was 7.7 years; 24 patients had at least 5 years of follow-up data. Frequency of stroke at presentation differed by subgroup (P < .001). Of patients with at least 2 years of follow-up, 33 (55%) experienced stroke. The proportion of patients experiencing stroke differed by subgroup (50% of idiopathic cases, 72% of sickle cell disease, 11% of neurofibromatosis, and 100% of Down syndrome, P = .003). The frequency of bilateral versus unilateral disease (P = .001) and stroke-free survival following presentation (P = .01) also differed by subgroup. CONCLUSIONS: In this single-center cohort, moyamoya subgroups differed with respect to clinical and radiographic characteristics, with neurofibromatosis-associated moyamoya syndrome having a milder phenotype and Down syndrome-associated moyamoya portending a more aggressive course. These findings need confirmation in a larger, multi-center cohort with longer duration of follow-up.

Optimization of Pediatric Bowel Management Using an Antegrade Enema Troubleshooting Algorithm.

BACKGROUND: A successful flush is the ability to flush through the appendicostomy or cecostomy channel, empty the flush through the colon, and achieve fecal cleanliness. We evaluated our experience with patients who were having flush difficulties based on a designed algorithm. METHODS: Eight patients with flush difficulties were initially evaluated. Based on the need for additional surgery versus changes in bowel management therapy (BMT), we developed an algorithm to guide future management. The algorithm divided flush issues into before, during, and after flushing. Children aged <20 y who presented with flush issues from September 2018 to August 2019 were evaluated to determine our algorithm's efficacy. Specific outcomes analyzed included changes in BMT versus need for additional surgery. RESULTS: After algorithm creation, 29 patients were evaluated for flush issues. The median age was 8.4 y (interquartile range: 6, 14); 66% (n = 19) were men. Underlying diagnoses included anorectal malformations (n = 17), functional constipation (n = 7), Hirschsprung's disease (n = 2), spina bifida (n = 2), and prune belly (n = 1). A total of 35 flush issues/complaints were noted: 29% before the flush, 9% during the flush, and 63% after the flush. Eighty percent of issues before the flush required surgical intervention, wherease 92% of issues during or after the flush were managed with changes in BMT. CONCLUSIONS: Most flush issues respond to changes in BMT. This algorithm can help delineate which types of flush issues would benefit from surgical intervention and what problems might be present if patients are not responding to changes in their flush regimen.

Large-scale identification of human cerebrovascular proteins: Inter-tissue and intracerebral vascular protein diversity.

The human cerebrovascular system is responsible for regulating demand-dependent perfusion and maintaining the blood-brain barrier (BBB). In addition, defects in the human cerebrovasculature lead to stroke, intracerebral hemorrhage, vascular malformations, and vascular cognitive impairment. The objective of this study was to discover new proteins of the human cerebrovascular system using expression data from the Human Protein Atlas, a large-scale project which allows public access to immunohistochemical analysis of human tissues. We screened 20,158 proteins in the HPA and identified 346 expression patterns correlating to blood vessels in human brain. Independent experiments showed that 51/52 of these distributions could be experimentally replicated across different brain samples. Some proteins (40%) demonstrated endothelial cell (EC)-enriched expression, while others were expressed primarily in vascular smooth muscle cells (VSMC; 18%); 39% of these proteins were expressed in both cell types. Most brain EC markers were tissue oligospecific; that is, they were expressed in endothelia in an average of 4.8 out of 9 organs examined. Although most markers expressed in endothelial cells of the brain were present in all cerebral capillaries, a significant number (21%) were expressed only in a fraction of brain capillaries within each brain sample. Among proteins found in cerebral VSMC, virtually all were also expressed in peripheral VSMC and in non-vascular smooth muscle cells (SMC). Only one was potentially brain specific: VHL (Von Hippel-Lindau tumor suppressor). HRC (histidine rich calcium binding protein) and VHL were restricted to VSMC and not found in non-vascular tissues such as uterus or gut. In conclusion, we define a set of brain vascular proteins that could be relevant to understanding the unique physiology and pathophysiology of the human cerebrovasculature. This set of proteins defines inter-organ molecular differences in the vasculature and confirms the broad heterogeneity of vascular cells within the brain.

Pediatric Testicular Torsion.

The pediatric patient presenting with acute scrotal pain requires prompt evaluation and management given the likelihood of testicular torsion as the underlying cause. Although other diagnoses can present with acute testicular pain, it is important to recognize the possibility of testicular torsion because the best chance of testicular preservation occurs with expeditious management. When testicular torsion is suspected, prompt surgical exploration is warranted. A delay in surgical management should not occur in an effort to obtain confirmatory imaging. When torsion is discovered, the contralateral testicle should undergo fixation to reduce the risk of asynchronous torsion.

Laparoscopic vs Open Pyeloplasty in Children: Results of a Randomized, Prospective, Controlled Trial.

PURPOSE: Open dismembered pyeloplasty is the preferred repair for ureteropelvic junction obstruction. Minimally invasive techniques have been applied to the original open approach but no clear advantage has been demonstrated for these technological advances. We evaluate outcomes between transperitoneal laparoscopic and open pyeloplasty in children. MATERIALS AND METHODS: All children 1 to 18 years old with ureteropelvic junction obstruction requiring operative repair were offered enrollment in the study. Patients were prospectively randomized to either laparoscopic or open pyeloplasty through a flank incision. RESULTS: A total of 50 patients in the laparoscopic group and 48 in the open group were enrolled from 2005 to 2014. Mean followup was similar between the groups (13.7 months in the laparoscopic group vs 12.3 months in the open group, p = 0.54). The only significantly different outcomes were for mean operative time, which was 139.5 minutes (range 94 to 213) in the laparoscopic group and 122.5 minutes (83 to 239) in the open group (p <0.01), and mean length of stay, which was 25.9 hours (18 to 143) in the laparoscopic group and 28.2 hours (16 to 73) in the open group (p = 0.02). Analgesic usage, success rate, total charges and all parameters in children older than 11 years were similar between the groups. CONCLUSIONS: Open and laparoscopic dismembered pyeloplasty are comparable and effective methods for repair of ureteropelvic junction obstruction. Although operative time was statistically shorter in the open group and length of stay was shorter in the laparoscopic group, the clinical significance of these variables is questionable. The approach to repair may best be based on family preference for incision aesthetics and surgeon comfort with either approach, rather than more classically objective outcome measures.

Laparoscopic Pyeloplasty for Ureteropelvic Junction Obstruction Following Open Pyeloplasty in Children.

OBJECTIVE: Few studies have evaluated the role of laparoscopic dismembered pyeloplasty in the setting of recurrent ureteropelvic junction (UPJ) obstruction following open dismembered pyeloplasty in the pediatric population. We present our experience at a single institution. PATIENTS AND METHODS: A retrospective analysis was performed of patients treated with laparoscopic pyeloplasty for secondary UPJ obstruction from March 2003 to August 2011 at a single institution. These patients were age and temporally matched with a control group of patients undergoing primary laparoscopic pyeloplasty. RESULTS: In total, 5 patients were identified as having undergone laparoscopic pyeloplasty for secondary UPJ obstruction following open dismembered pyeloplasty. Operative time was longer in the secondary repair group compared with the control group (190 versus 141 minutes; P = .24), although this was complicated by 1 patient in the secondary repair group undergoing multiple procedures. Morphine equivalent use and length of stay were similar (4.1 versus 6.6 mg [P = .21] and 1.4 versus 1.2 days [P = .67] in control patients versus secondary repair patients, respectively). All of the 5 (100%) patients undergoing secondary repair had successful outcomes with improved hydronephrosis on ultrasound, and 4 of 4 (100%) had improved or normal T½ times on postoperative mercaptoacetyltriglycine (MAG3) renal scan. One family in each group declined the renal scan for personal reasons. No complications were noted with a mean follow-up time of 13 months in both groups. CONCLUSIONS: Laparoscopic repair of secondary UPJ obstruction is a well-tolerated and effective option. When this technique is compared with primary laparoscopic pyeloplasty, results appear equivalent even after failed open repair, with comparable postoperative narcotic requirement and length of stay. Further studies are needed to better define the role of secondary laparoscopic pyeloplasty in the pediatric population, especially with regard to cost compared with other open and minimally invasive techniques.

Surgical Approaches to Pediatric Ureteropelvic Junction Obstruction.

Approximately 10-30% of infants with hydronephrosis are found to have ureteropelvic junction (UPJ) obstruction. Technological advances in imaging have allowed physicians to better identify the location of the obstruction. The classic repair is the Anderson-Hynes repair which shows a 90-100% success rate and appears superior to many less complex techniques. Is it best to approach this repair through an open incision or laparoscopically with or without a surgical robot? That question remains to be answered and largely depends on how you define "best."

Improved robotic stereotactic body radiation therapy plan quality and planning efficacy for organ-confined prostate cancer utilizing overlap-volume histogram-driven planning methodology.

BACKGROUND AND PURPOSE: This study is to determine if the overlap-volume histogram (OVH)-driven planning methodology can be adapted to robotic SBRT (CyberKnife Robotic Radiosurgery System) to further minimize the bladder and rectal doses achieved in plans manually-created by clinical planners. METHODS AND MATERIALS: A database containing clinically-delivered, robotic SBRT plans (7.25 Gy/fraction in 36.25 Gy) of 425 patients with localized prostate cancer was used as a cohort to establish an organ's distance-to-dose model. The OVH-driven planning methodology was refined by adding the PTV volume factor to counter the target's dose fall-off effect and incorporated into Multiplan to automate SBRT planning. For validation, automated plans (APs) for 12 new patients were generated, and their achieved dose/volume values were compared to the corresponding manually-created, clinically-delivered plans (CPs). A two-sided, Wilcoxon rank-sum test was used for statistical comparison with a significance level of p<0.05. RESULTS: PTV's V(36.25 Gy) was comparable: 95.6% in CPs comparing to 95.1% in APs (p=0.2). On average, the refined approach lowered V(18.12 Gy) to the bladder and rectum by 8.2% (p<0.05) and 6.4% (p=0.14). A physician confirmed APs were clinically acceptable. CONCLUSIONS: The improvements in APs could further reduce toxicities observed in SBRT for organ-confined prostate cancer.

Using electrospun poly(ethylene-oxide) nanofibers for improved retention and efficacy of bacteriolytic antibiotics.

The aim of this study was to demonstrate targeted delivery of protein-based bactericidal antibiotics using electrospun polymer nanofibers. Previous studies have utilized electrospinning to create nanofibers for the localized delivery of therapeutic agents, including non-steroidal anti-inflammatory drugs (NSAIDs) and low molecular weight heparin. By employing established electrospinning techniques, nanofibers of varying diameters (100-500 nm) were generated from a 0.05 % solution of poly(ethylene-oxide) (PEO) and the antimicrobial peptide, LL-37 was incorporated into the nanofiber meshwork. Initial experiments determined that the strong electric fields caused by electrospinning do not disrupt the antimicrobial properties of LL-37, thus justifying the application of LL-37 as an electrospun component. Disk diffusion assays and especially bacterial filtration studies with E. coli were conducted to quantify the drug delivery potential of the nanofibers. Disk diffusion revealed a small zone of inhibition of about 1 mm around the LL-37-incorporated nanofiber disk. Filtration tests demonstrated that electrospun PEO fibers were capable of delivering LL-37 consistently while still maintaining their antimicrobial abilities.