Local and Regional Recurrences of Clinically Localized Renal Cell Carcinoma after Nephrectomy: A 15 Year Institutional Experience with Prognostic Features and Oncologic Outcomes.

OBJECTIVE: To evaluate outcomes for patients with local recurrence (LR) of clinically localized renal cell carcinoma (RCC) without concurrent systemic metastasis from our institution, an event that occurs rarely (1%-3%) after surgery. LR may be a harbinger of poor outcomes, and the best management of these patients is unclear. MATERIALS/METHODS: We retrospectively reviewed patients surgically treated for clinically localized RCC (cT1-2N0M0) with subsequent LR (in the partial or radical nephrectomy bed) and/or regional recurrence (RR; in the abdomen distant from the direct site of surgery) without concurrent metastasis from our institutional database (2004-2018). Comparative and survival analyses were performed. RESULTS: Out of 3038 total patients, 1895 had clinically localized RCC, with 30 patients (1.6%) having isolated LR/RR. Median time to recurrence was 26.5 months (IQR:16-35). Of 26 patients treated with local therapy, 14 (53.8%) recurred over a median follow-up time of 29.5 months (IQR:12-45). The 1-year and 2-year secondary recurrence-free survival rates are 60.7% and 49.7%, respectively. Two or more sites of locoregional recurrence significantly predicted secondary recurrence/metastasis after local therapy for local recurrence (hazard ratio: 2.22, P= .04). CONCLUSION: Our results suggest local therapy is appropriate for select patients with LR/RR, with almost 50% of patients undergoing a second local therapy remaining alive with "local cure" and no secondary recurrence. The number of sites of recurrence can be used to better select patients that will benefit from local therapy or systemic/combination therapy. This work provides a framework onto which further studies regarding local therapy and locoregional recurrence of RCC can be performed.

Phosphodiesterase type 5 inhibitor therapy provides sustained relief of symptoms among patients with chronic pelvic pain syndrome.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome type III (CP/CPPS) is associated with pelvic pain, sexual dysfunction and irritative voiding. Sustained symptom relief has proven difficult with alpha blockers, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs). Phosphodiesterase type 5 (PDE5) inhibitors (PDE5is) have the potential to alleviate bladder urgency, relax the pelvic floor, and correct underlying erectile dysfunction; however, few studies have investigated the application of PDE5i's to CP/CPPS. The purpose of this study was to assess the effect of long-term PDE5i therapy on symptoms among patients with diagnosed CP/CPPS. METHODS: A group of patients older than 18 years diagnosed with CP/CPPS presenting from 2009 to 2018 were followed prospectively while they were being prescribed off-label PDE5i therapy for symptoms. National Institute of Health chronic prostatitis symptom index (CPSI) scores before PDE5i therapy initiation and after at least 3 months were utilized to assess impact on symptoms. RESULTS: A total of 25 patients (mean age 44.4±12.9 years) met study criteria. The mean duration of PDE5i therapy was 1.3±1.6 years. Continued use of daily PDE5is was associated with significant decreases in total CPSI, pain, urinary symptom and quality of life scores [total CPSI: -12.8, standard deviation (SD) 9.5; pain: -6.1, SD 4.1; urinary symptoms: -2.4, SD 2.1; quality of life: -4.5, SD 3.9; P<0.001]. CONCLUSIONS: This prospective data suggests that PDE5i therapy is associated with durable decreases in CP/CPPS symptoms past 3 months.

Pediatric Frontal Bone and Sinus Fractures: Cause, Characteristics, and a Treatment Algorithm.

BACKGROUND: The purpose of this study was to assess the incidence, cause, characteristics, presentation, and management of pediatric frontal bone fractures. METHODS: A retrospective cohort review was performed on all patients younger than 15 years with frontal fractures that presented to a single institution from 1998 to 2010. Charts and computed tomographic images were reviewed, and frontal bone fractures were classified into three types based on anatomical fracture characteristics. Fracture cause, patient demographics, management, concomitant injuries, and complications were recorded. Primary outcomes were defined by fracture type and predictors of operative management and length of stay. RESULTS: A total of 174 patients with frontal bone fractures met the authors' inclusion criteria. The mean age of the patient sample was 7.19 ± 4.27 years. Among these patients, 52, 47, and 75 patients were classified as having type I, II, and III fractures, respectively. A total of 14, 9, and 24 patients with type I, II, and III fractures underwent operative management, respectively. All children with evidence of nasofrontal outflow tract involvement and obstruction underwent cranialization (n = 11). CONCLUSIONS: The authors recommend that type I fractures be managed according to the usual neurosurgical guidelines. Type II fractures can be managed operatively according to the usual pediatric orbital roof and frontal sinus fracture indications (e.g., significantly displaced posterior table fractures with associated neurologic indications). Lastly, type III fractures can be managed operatively as for type I and II indications and for evidence of nasofrontal outflow tract involvement. The authors recommend cranialization in children with nasofrontal outflow tract involvement. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Association Between Saccule and Semicircular Canal Impairments and Cognitive Performance Among Vestibular Patients.

OBJECTIVES: Growing evidence suggests that vestibular function impacts higher-order cognitive ability such as visuospatial processing and executive functioning. Despite evidence demonstrating vestibular functional impairment impacting cognitive performance, it is unknown whether cognitive ability is differentially affected according to the type of vestibular impairment (semicircular canal [SCC] versus saccule) among patients with diagnosed vestibular disease. DESIGN: Fifty-four patients who presented to an academic neurotologic clinic were recruited into the study. All patients received a specific vestibular diagnosis. Forty-one patients had saccule function measured with the cervical vestibular-evoked myogenic potential, and 43 had SCC function measured using caloric irrigation. Cognitive tests were administered to assess cognitive performance among patients. One hundred twenty-five matched controls were recruited from the Baltimore Longitudinal Study of Aging to compare cognitive performance in patients relative to age-matched healthy controls. RESULTS: Using multivariate linear regression analyses, patients with bilaterally absent cervical vestibular-evoked myogenic potential responses (i.e., bilateral saccular impairments) were found to take longer in completing the Trail-Making test (ß = 25.7 sec, 95% confidence interval = 0.3 to 51.6) and to make significantly more errors on the Benton Visual Retention test part-C (ß = 4.5 errors, 95% confidence interval [CI] = 1.2 to 7.8). Patients with bilateral SCC impairment were found to make significantly more errors on the Benton Visual Retention test part-C (ß = 9.8 errors, 95% CI = 0.2 to 19.4). From case-control analysis, for each SD difference in Trail-Making test part-B time, there was a corresponding 142% increase in odds of having vestibular impairment (odds ratio = 2.42, 95% CI = 1.44 to 4.07). CONCLUSIONS: These data suggest that bilateral saccule and SCC vestibular impairments may significantly affect various domains of cognitive performance. Notably, the cognitive performance in patients in this study was significantly poorer relative to age-matched healthy adults. Cognitive assessment may be considered in patients with saccule and SCC impairments, and cognitive deficits in vestibular patients may represent an important target for intervention.

Urothelial carcinoma within the prostatic utricle of an adult with hypospadias and Fanconi anemia.

Prostatic utricles are rare in the general population and are often otherwise unremarkable anatomic variants. These structures are contiguous with the prostatic urethra and are nevertheless susceptible to urothelial carcinoma. This case report discusses the first reported patient with Fanconi anemia with urothelial carcinoma within an enlarged prostatic utricle.

What Do Plastic Surgery Patients Think of Financial Conflicts of Interest and the Sunshine Act?

BACKGROUND: The purpose of this study was to evaluate patients' views of conflicts of interest (COI) and their comprehension of recent legislation known as the Physician Payments Sunshine Act. This report constitutes the first evaluation of plastic surgery patients' views on COI and the government-mandated Sunshine Act. METHODS: This cross-sectional study invited patients at an academic, general plastic surgery outpatient clinic to complete an anonymous survey. The survey contained 25 questions that assessed respondents' perceptions of physician COI and awareness of the Sunshine Act. Analyses were performed to examine whether perspectives on COI and the Sunshine Act varied by level of education or age. RESULTS: A total of 361 individuals completed the survey (90% response rate). More than half of respondents with an opinion believed that COI would affect their physician's clinical decision-making (n = 152, 52.9%). Although almost three fourths (n = 196, 71.2%) believed that COI should be regulated and COI information reported to a government agency, the majority were not aware of the Sunshine Act before this survey (n = 277, 81.2%) and had never accessed the database (n = 327, 95.9%). More than half of patients (n = 161, 59.2%) stated that they would access a publicly available database with physicians' COI information. A larger proportion of older and educated patients believed that regulation of physicians' COI was important (P < 0.001). CONCLUSIONS: Awareness of and access to plastic surgeon COI information is low among plastic surgery patients. Older and more educated patients believed that transparency regarding COI is important with regard to their clinical care.

Health-related quality of life and economic burden of vestibular loss in older adults.

Objectives: Vestibular loss is a debilitating condition, and despite its high prevalence in older adults, the quality of life (QoL) burden of vestibular loss in older individuals has not been well-studied. This report quantifies the impact on overall QoL and identifies domains of health most affected. We hypothesize vestibular loss will be associated with impairment in diverse domains of health-related QoL. Study Design: Prospective, case-control study. Methods: A convenience sample of 27 patients age ≥60 years with vestibular physiologic loss was recruited from an academic neurotology clinic. The patients did not have any identifiable cause of their vestibular loss other than aging. The convenience sample was compared to an age-matched cross-sectional sample of the general US population (n = 1266). The main outcome was QoL measured by the Ontario Health Utilities Index Mark III (HUI3). Results: Compared to the general population, patients with vestibular loss had significantly lower overall unadjusted HUI3 scores (-0.32, p < 0.001). Multivariate regression analysis showed vestibular loss was significantly associated with poorer performance in vision (-0.11 p < 0.0001), speech (-0.15, p < 0.0001), dexterity (-0.13, p < 0.0001), and emotion (-0.07, p = 0.0065). Adjusted aggregate HUI3 was also significantly lower for vestibular loss (-0.15, p = 0.0105). These QoL decrements resulted in an average loss of 1.30 Quality-Adjusted Life Years (QALYs). When using a $50,000/QALY willingness-to-pay threshold, vestibular loss was associated with a $64,929 lifetime economic burden per affected older adult, resulting in a total lifetime societal burden of $227 billion for the US population ≥60 years of age. Conclusions: Loss of vestibular function with aging significantly decreases quality of life across multiple domains of well-being. These QoL reductions are responsible for heavy societal economic burdens of vestibular loss, which reveal potential benefits of prompt diagnosis and treatment of this condition. Level of Evidence: 3.

Impact of molecular weight on the intrinsic immunogenic activity of poly(beta amino esters).

Polymeric carriers are ubiquitously studied in vaccine and drug delivery to control the encapsulation, kinetics, and targeting of cargo. Recent research reveals many polymers can cause immunostimulatory and inflammatory responses, even in the absence of other immune signals. However, the extent to which this intrinsic immunogenicity evolves during degradation is understudied. Here we synthesized a small library of poly(beta amino esters) (PBAEs) that exhibit different starting molecular weights (MWs), but with similar and rapid degradation rates. Primary dendritic cells (DCs) treated with free PBAEs, either intact or degraded to form low MW fragments, were not activated. In contrast particles formed from PBAEs at different extents of degradation caused differential expression of classical DC activation markers (for example, CD40, CD80, CD86, MHCII), as well as antigen presentation. During degradation, activation levels changed with changing physicochemical properties (for example, MW, concentration, size, charge). Of note, irrespective of starting MW, immunogenicity peaked when the MW of degrading PBAEs decreased to a range of ∼1500-3000 Da. These findings could help inform design of future carriers that exploit the dynamic interactions with the immune system as materials degrade, leading to carriers that deliver cargo but also help direct the immune responses to vaccine or immunotherapy cargo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1219-1229, 2017.

Persistence and Recurrence Following Femoral Derotational Osteotomy in Ambulatory Children With Cerebral Palsy.

BACKGROUND: Excessive hip internal rotation is frequently seen in children with cerebral palsy (CP). Femoral derotational osteotomy (FDO) is effective in the short term, but factors associated with long-term correction remain unclear. The purposes of this study were to define the incidence of persistence and recurrence of hip internal rotation following FDO in ambulatory children with CP and to evaluate factors that influence outcome. METHODS: Following IRB approval, kinematic and passive range of motion (PROM) variables were retrospectively evaluated in children with spastic CP who had FDO to correct hip internal rotation as part of clinical care at a children's specialty hospital. Children included had a preoperative evaluation (Vpre), a short-term postoperative evaluation (Vshort, 1 to 3 y post), and, in some cases, a long-term postoperative evaluation (Vlong, ≥5 y post). Age at surgery, physical exam measures, and kinematics variables were evaluated as predictors for dynamic and static recurrence. RESULTS: Kinematic hip rotation improved from 14±12 degrees (Vpre; internal positive) to 4±13 degrees (Vshort) and relapsed to 9±15 degrees long term (P<0.05 Vpre/Vshort/Vlong; 99 limbs). Hip PROM midpoint improved from 23±9 degrees (Vpre) to 8±11 degrees (Vshort) and relapsed to 14±13 degrees (P<0.01 Vpre/Vshort/Vlong). Persistent hip internal rotation was noted in 41% (kinematics) and 18% (PROM) of limbs at Vshort (105 children, 178 limbs). Of limbs that showed initial improvement at Vshort (62 children, 95 limbs), recurrence was seen in 40% (kinematic hip rotation) and 39% (hip midpoint) at Vlong. Comparing children who had recurrent hip internal rotation and those who maintained long-term correction, we saw higher levels of spasticity and lower gait velocity in the recurrent group (P<0.05). CONCLUSIONS: Although FDO is an accepted treatment in children with CP, persistence and recurrence of hip internal rotation can occur. Recurrence is associated with spasticity and slower gait velocity. Predictor variables may be useful for surgeons during preoperative discussions of expected outcome with families of FDO candidates. LEVEL OF EVIDENCE: Level III.

Intrinsic immunogenicity of rapidly-degradable polymers evolves during degradation.

Recent studies reveal many biomaterial vaccine carriers are able to activate immunostimulatory pathways, even in the absence of other immune signals. How the changing properties of polymers during biodegradation impact this intrinsic immunogenicity is not well studied, yet this information could contribute to rational design of degradable vaccine carriers that help direct immune response. We use degradable poly(beta-amino esters) (PBAEs) to explore intrinsic immunogenicity as a function of the degree of polymer degradation and polymer form (e.g., soluble, particles). PBAE particles condensed by electrostatic interaction to mimic a common vaccine approach strongly activate dendritic cells, drive antigen presentation, and enhance T cell proliferation in the presence of antigen. Polymer molecular weight strongly influences these effects, with maximum stimulation at short degradation times--corresponding to high molecular weight--and waning levels as degradation continues. In contrast, free polymer is immunologically inert. In mice, PBAE particles increase the numbers and activation state of cells in lymph nodes. Mechanistic studies reveal that this evolving immunogenicity occurs as the physicochemical properties and concentration of particles change during polymer degradation. This work confirms the immunological profile of degradable, synthetic polymers can evolve over time and creates an opportunity to leverage this feature in new vaccines. STATEMENT OF SIGNIFICANCE: Degradable polymers are increasingly important in vaccination, but how the inherent immunogenicity of polymers changes during degradation is poorly understood. Using common rapidly-degradable vaccine carriers, we show that the activation of immune cells--even in the absence of other adjuvants--depends on polymer form (e.g., free, particulate) and the extent of degradation. These changing characteristics alter the physicochemical properties (e.g., charge, size, molecular weight) of polymer particles, driving changes in immunogenicity. Our results are important as many common biomaterials (e.g., PLGA) are now known to exhibit immune activity that alters how vaccines are processed. Thus, the results of this study could contribute to more rational design of biomaterial carriers that also actively direct the properties of responses generated by vaccines.