Investigation of anti-PEG antibody response to PEG-containing cosmetic products in mice.

Polyethylene glycol (PEG), a polyether compound, is available in molecular weights from ∼300 g/mol to ∼10,000,000 g/mol. In the molecular weight range of ∼750 to ∼5000, PEG is commonly used in bioconjugation technology and nano-formulations to improve the circulation half-life of the formulations and increase their stability. In cosmetics, lower molecular weight PEG compounds such as PEG 60 or PEG 100 are widely used as emulsifiers and skin penetration enhancers. PEG polymers are generally recognized as biologically inert and non-immunogenic. However, it is recently reported that the "pre-existing" anti-PEG antibodies have been detected in high percentages of healthy individuals who have never received treatment with parenteral PEGylated formulations. To the best of our knowledge, we are the first to attempt to find an explanation for the source of pre-existing anti-PEG antibodies in healthy individuals. In a murine study, we demonstrated that topically applied PEG derivatives, present in two commercially available cosmetic products, could efficiently penetrate the stratum corneum and reach the systemic circulation. The skin penetration of PEG derivatives was further enhanced in injured or otherwise compromised skin. Daily application of cosmetic PEG derivatives primed the immune system, inducing anti-PEG IgM production. Anti-PEG IgM was detected by Day 14 in mice with normal skin, while anti-PEG IgM was detected as early as day 7 in mice with compromised skin. In addition, in mice with pre-induced circulating levels of anti-PEG IgM, topically applied PEG derivatives from cosmetic products appeared to bind to the pre-induced anti-PEG IgM, lowering blood levels. Current results indicate that PEG derivatives in cosmetic products may be an important contributor to the source of the "pre-existing" anti-PEG antibodies that have been detected in healthy individuals.

Iatrogenic Ureterocolic Fistula in Pediatric Age Group: A Case Report and Review of the Literature.

Ureteral injury is one of the major complications related to colorectal and gynecologic procedures. Injuries are sometimes identified intraoperatively, but the diagnosis of ureteral injury is often delayed. Ureterocolic fistula is a relatively rare condition and mostly due to obstructing calculi, diverticular disease of the colon, radiotherapy, cancer, or trauma. Here in, we present a boy with an iatrogenic left ureterocolic fistula following multiple colonic surgeries that were complicated by an un-noticed left ureteric injury. This injury was not diagnosed early and the patient presented later with recurrent UTIs and decreased left differential renal function which necessitated open left nephroureterectomy.

Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products.

Polyethylene glycol (PEG) is a versatile polymer that is widely used as an additive in foods and cosmetics, and as a carrier in PEGylated therapeutics. Even though PEG is thought to be less immunogenic, or perhaps even non-immunogenic, with a variety of physicochemical properties, there is mounting evidence that PEG causes immunogenic responses when conjugated with other materials such as proteins and nanocarriers. Under these conditions, PEG with other materials can result in the production of anti-PEG antibodies after administration. The antibodies that are induced seem to have a deleterious impact on the therapeutic efficacy of subsequently administered PEGylated formulations. In addition, hypersensitivity to PEGylated formulations could be a significant barrier to the utility of PEGylated products. Several reports have linked the presence of anti-PEG antibodies to incidences of complement activation-related pseudoallergy (CARPA) following the administration of PEGylated formulations. The use of COVID-19 mRNA vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs), has recently gained wide acceptance, although many cases of post-vaccination hypersensitivity have been documented. Therefore, our review focuses not only on the importance of PEGs and its great role in improving the therapeutic efficacy of various medications, but also on the hypersensitivity reactions attributed to the use of PEGylated products that include PEG-based mRNA COVID-19 vaccines.

Pediatric metanephric adenoma with Fanconi-Bickel syndrome: a case report and review of literature.

BACKGROUND: Metanephric adenoma (MA) is a rare benign renal tumor that resembles renal cell carcinoma and Wilms' tumor in radiological as well as pathological appearance. It can present at any age or gender, and it is extremely rare in the pediatric age group with less than 50 reported cases. Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism. Herein, we report a rare incidence of MA in a boy with a genetically confirmed FBS who underwent a nephron-sparing surgery. CASE PRESENTATION: A 21-month-old boy was referred to the pediatric urology clinic for further evaluation of an incidentally discovered left renal mass. His laboratory investigations showed normal renal function, hypophosphatemia, high blood glucose level, markedly elevated serum alkaline phosphatase, and low serum vitamin D. Blood picture showed signs of polycythemia and urinalysis showed glucosuria and aminoaciduria. Genetic testing was positive for Fanconi-Bickel syndrome. Radiological investigations were carried out with abdominal ultrasound and computerized tomography (CT) with intravenous contrast documented a sharply marginated peripheral hypoechoic hypovascular homogeneously enhancing mass at the upper pole of the left kidney measuring 2.0 × 1.8 × 2.0 cm. The child was admitted and started on supportive treatment until his medical condition was stabilized, then underwent elective open left partial nephrectomy via a left upper transverse abdominal transperitoneal incision. The excised renal mass was sent for histopathological assessment and was found to be a tumor composed of tightly packed tubules with no mitotic figures or necrosis and scanty cytoplasm consistent with MA. After good hydration and tumor resection, his polycythemia gradually improved. The patient was discharged home in a good condition with his proper replacement therapies. His follow-up abdominal ultrasound after 12 months showed no signs of recurrence. CONCLUSIONS: Metanephric adenoma is extremely rare in the pediatric age group, especially in those who have a FBS. The only way to diagnose and treat this tumor is by surgical resection as most patients are asymptomatic. A nephron-sparing surgery is better for this age group in which the future renal function is considered.

Reoperation for Channel Complications in Children With Continent Cutaneous Catheterizable Channels: The Test of Time.

OBJECTIVES: To examine the durability of continent cutaneous catheterizable urinary channels (CCCC) in children and assess whether channel complications continue to arise with extended follow-up. Previous studies demonstrated that complications of CCCC cluster in the early years following surgery. METHODS: The database of a tertiary center was queried for patients≤21 years who underwent CCCC. Patients with <6 years of follow-up were excluded. Patients were invited for follow-up to assess continence. Clinic visits and hospital admissions were reviewed for channel complications requiring reoperation. Complications were analyzed against patient and channel characteristics and time since initial surgery. RESULTS: Between 1993 and 2012, a total of 120 patients underwent CCCC at a median age of 6.8(0.4-21) years and a median follow-up of 11.4(6.6-27) years. CCCC were created using the appendix, Monti channels and tapered ileal segments in 74(61.7%), 33(27.5%) and 13(10.8%), respectively. Continence relied on the extra-mural serous lined principle in 85.8% and the stoma was anastomosed to the umbilicus in 90%. Dryness with catheterization intervals of 3 hours or longer was eventually achieved in 90.8% with similar rates among different channel types (P=.149). 26(21.7%) required 42 interventions to treat channel complications with 32.5% occurring >5 years following initial surgery irrespective of the channel type (P=.978). On multivariate analysis, ileal channels had 3.372 higher odds of needing reoperation compared to appendicovesicostomy (95%CI=1.240-9.166; P = .037). CONCLUSION: A high reoperation rate is anticipated throughout the lifetime of CCCC. Appendicovesicostomy has a low complication risk relative to ileal channels.

Budesonide-Loaded Eudragit S 100 Nanocapsules for the Treatment of Acetic Acid-Induced Colitis in Animal Model.

Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues as insufficient drug amount at diseased regions, high adverse effects of released drugs, and unintentionally premature drug release to noninflamed gastrointestinal regions. Herein, the prepared budesonide-loaded Eudragit S 100/Capryol 90 nanocapsules for the treatment of inflammatory bowel disease. Nanocapsules were prepared efficiently by nanoprecipitation technique and composed mainly of the pH-sensitive Eudragit S 100 polymeric coat with a semisynthetic Capryol 90 oily core. Full 31 × 21 factorial design was applied to obtain optimized nanocapsules. Optimal nanocapsules showed mean particle size of 171 nm with lower polydispersity index indicating the production of monodispersed system and negative zeta-potential of - 37.6 mV. Optimized nanocapsules showed high encapsulation efficiency of 83.4% with lower initial rapid release of 10% for first 2 h and higher rapid cumulative release of 72% after 6 h. The therapeutic activity of the prepared budesonide-loaded nanocapsules was evaluated using a rat colitis model. Disease activity score, macroscopical examination, blood glucose level, and histopathological assessment showed marked improvements over that free drug suspension. Obtained results demonstrate that the budesonide-loaded Eudragit S 100 nanocapsules are an effective colon-targeting nanosystem for the treatment of inflammatory bowel disease. Capryol 90 was found to be a successful, and even preferred, alternative to benzyl benzoate, which is commonly employed as the oil core of such nanocapsules.

Does grafted tubularized incided plate improve the outcome after repair of primary distal hypospadias: A prospective randomized study?

OBJECTIVE: To detect whether grafting the incised plate during Snodgrass repair would improve outcome. MATERIALS AND METHODS: Sixty patients with primary distal hypospadias were included. Patients were equally randomized using closed envelop method to either Snodgrass or grafted tubularized incised plate repair (GTIP). All operations were performed by a single surgeon. All intaroperative data were recorded. All patients were followed up for 1 year. Success was defined as slit shaped meatus at the tip of the glans with no stenosis, fistula or diverticulum. RESULTS: All 60 patients were evaluated at 1 year of follow-up. Mean age at surgery was 40±15months. Both groups were comparable as regard to patients' age, meatus location, length and width and depth of urethral plate and glans width. Success was documented in 29/30 patients (96.7%) in the Snodgrass group. The only complication was meatal stenosis in one patient, whereas success was documented in 28/30 patients (93.3%) in the GTIP group. The two failures were secondary to partial glans dehiscence. Success rate was not statistically different. Flow rate data at 1 year showed insignificant difference between both groups as regards Q-max and voiding time. The only statistically significant difference between both groups was a longer operative time 106±12min in the GTIP group compared to only 77±9 for the Snodgrass group (p = 0.005). CONCLUSIONS: Snodgrass and GTIP techniques for primary distal hypospadias repair have similar outcome. With a significantly shorter operative time, Snodgrass repair remains the first choice for primary distal hypospadias repair. TYPE OF THE STUDY: Prospective randomized study. LEVEL OF EVIDENCE: Level I.

Perineal Hernia Is an Unusual Complication Post Perineal Bladder Neck Closure: A Case Report.

Bladder neck closure (BNC) is the ultimate bladder neck reconstruction. If reconstruction fails, closure must be considered as it gives the highest continence rate. The vast majority of BNCs are performed through an abdominal approach (either transvesical or extravesical approach), but perineal approach remains an option for BNC with considerable success rate. Perineal hernia, which is defined as protrusion of abdominal contents through the perineal defect, is a very rare complication after urologic procedures. We report a case of perineal hernia post perineal BNC.

Stone culture retrieved during percutaneous nephrolithotomy: is it clinically relevant?

Stone culture has been frequently investigated following percutaneous nephrolithotomy (PNL) in the last decade. We aimed to crucially define the clinical role of stone culture in modifying the treatment plan in patients with postoperative sepsis. Between June 2012 and April 2013, a total of 79 consecutive PNL procedures were included. Perioperative data were prospectively maintained. Preoperative urine sample, retrieved stone fragments and postoperative nephrostomy tube urine sample were cultured and antibiotic sensitivity tests were performed. The occurrence of at least two of the systemic inflammatory response syndrome (SIRS) events during their inpatient stay was diagnostic of SIRS. The antibiotic regimen utilized and its modifications were reported. The preoperative culture was positive in 26 patients (32.9 %). The culture of stone fragments showed significant bacterial growth in 23 (29.1 %) cases. Significant growth on stone culture was significantly associated with the presence of preoperative urinary catheters and positive preoperative urine culture (P = 0.001, 0.006 respectively). Postoperative culture was positive in only six patients (7.6 %). SIRS was diagnosed in the first postoperative day in 12 patients (15.2 %). Leukocytosis was the only predictor of SIRS. Neither preoperative culture, stone culture nor postoperative culture was predictor of SIRS. Stone culture was positive in four patients with SIRS. Stone culture changed the treatment plan in only one patient. Our data do not support the routine implementation of stone culture in the PNL workup, as it did not indicate a change of antibiotic regimen in most of the cases.

Is there a way to predict failure after direct vision internal urethrotomy for single and short bulbar urethral strictures?

OBJECTIVE: To identify patient and stricture characteristics predicting failure after direct vision internal urethrotomy (DVIU) for single and short (<2 cm) bulbar urethral strictures. PATIENTS AND METHODS: We retrospectively analysed the records of adult patients who underwent DVIU between January 2002 and 2013. The patients' demographics and stricture characteristics were analysed. The primary outcome was procedure failure, defined as the need for regular self-dilatation (RSD), redo DVIU or substitution urethroplasty. Predictors of failure were analysed. RESULTS: In all, 430 adult patients with a mean (SD) age of 50 (15) years were included. The main causes of stricture were idiopathic followed by iatrogenic in 51.6% and 26.3% of patients, respectively. Most patients presented with obstructive lower urinary tract symptoms (68.9%) and strictures were proximal bulbar, i.e. just close to the external urethral sphincter, in 35.3%. The median (range) follow-up duration was 29 (3-132) months. In all, 250 (58.1%) patients did not require any further instrumentation, while RSD was maintained in 116 (27%) patients, including 28 (6.5%) who required a redo DVIU or urethroplasty. In 64 (6.5%) patients, a redo DVIU or urethroplasty was performed. On multivariate analysis, older age at presentation [odds ratio (OR) 1.017; P = 0.03], obesity (OR 1.664; P = 0.015), and idiopathic strictures (OR 3.107; P = 0.035) were independent predictors of failure after DVIU. CONCLUSION: The failure rate after DVIU accounted for 41.8% of our present cohort with older age at presentation, obesity, and idiopathic strictures independent predictors of failure after DVIU. This information is important in counselling patients before surgery.

Wandering nematode in the vitreous cavity.

BACKGROUND: Bancroftian filariasis is focally endemic in Egypt. There have been many reports of intraocular filariasis; the question of why one filarial nematode should cause ocular disease while another does not may be related to the behavior of the microfilaria and the location of the cross-reacting ocular antigen. METHODS: A 35-year-old woman with a white worm approximately 3 disk diameters in length penetrating the left macula, moving in the vitreous cavity, with a part of its length in the vitreous cavity while the rest was embedded subretinally, is described. Pars plana vitrectomy was performed and the worm was aspirated successfully. RESULTS: Parasitologic study of the aspirated worm identified juvenile Wuchereria bancrofti. Ivermectin 150 µg/kg was given orally to the patient after identification of the worm. Six weeks later, the patient's visual acuity had improved to 20/200. CONCLUSION: Intravitreal parasites should be surgically removed as soon as possible.