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PURPOSE To report a case of vitreous seeding in a medium-sized choroidal melanoma and review the literature. METHODS Observational case report and review of literature for pathogenesis, role of vitreous biopsy, and treatment outcomes. RESULTS A case of 57-year-old man diagnosed with vitreous seeding in the left eye 1 year after episcleral brachytherapy for medium-sized choroidal melanoma. The patient was initially diagnosed to have subretinal and vitreous hemorrhage due to rupture of a retinal artery macroaneurysm for which focal laser and intravitreal antivascular endothelial growth factor injections were administered. Over the next 9 months, the vitreous hemorrhage cleared and choroidal melanoma with retinal invasion became evident. One year after brachytherapy, the primary tumor regressed with resolution of surrounding subretinal fluid and hemorrhage. However, gradual decline in the visual acuity from 20/50 to 20/500 with increase of pigmented debris over the retinal surface and in the vitreous cavity was noted. A vitreous biopsy confirmed the presence of viable melanoma cells (epithelioid type), and the eye was enucleated. Histopathology showed microscopic persistence of primary tumor with diffuse vitreous seeding. CONCLUSION Vitreous seeding of choroidal melanoma poses a diagnostic and management challenge.

Purpose: To describe methods of risk assessment in twins with retinoblastoma (RB). Methods: A case series of four RB probands with a twin sibling. Family status, clinical presentation, and RB1 germline status-based risk assessment were analyzed. Results: Two pairs had a positive family history (unilateral and bilateral RB in one of the parents (#1 and #2, respectively) and two pairs (#3 and #4) were sporadic. One of the familial twins (#1) had a high risk (90%) of manifesting RB in the twin. The other case (#2) with an absent RB1 germline mutation in the twin had a 0% risk of developing RB. Among sporadic cases of twins (#3), genetic testing did not identify a germline mutation (tumor sample unavailable) in the proband which downgraded the risk of germline mutation from 15% to T) could be identified (tumor tissue available) in the proband (# 4). Identical germline mutation (and RB tumor) was also noted in the twin. In each case, there was concordance between the assessed risk and manifestation of RB. Conclusion: Assessment of risk of RB in a twin presents with a unique challenge. Depending upon the genotype variant, the risk of developing RB can vary from 0% to 90%. In addition to family history, clinical manifestation in the proband, zygosity status, and RB1 germline status are critical in formulating risk-appropriate surveillance guidelines.

Purpose: The published data on ocular survival following intravenous chemotherapy of retinoblastoma (RB) seems to be skewed by evolving practice patterns induced by use of intravitreal chemotherapy (iVitc). We aimed to explore potential role of iVitc for vitreous seeding for patients treated with intravenous chemotherapy (IVC). Methods: A literature search was performed to identify cases of RB treated with primary IVC prior to advent of iVitc by various search engines (PubMed, Medline, and Google) from 1992 to 2018. Studies were excluded if number of cases were less than 40 or lacked data related to type of recurrence and its treatment. Rates and patterns of recurrence and its management were categorized. Results: Out of 15 studies identified, only 10 studies (797 eyes) met the inclusion criteria. The mean age at presentation was 15.3 months (range 0–192.8 months). Unilateral cases represented 25% of the cohort. The ocular survival rate with primary IVC was 63% (500/797 eyes). Of the 297 eyes (37%) that failed IVC therapy, additional 99 eyes could be salvaged with EBRT (599/797 eyes, 75%). Remaining 198 eyes were enucleated (198/797 eyes 25%). K-M survival analysis could not be done due lack of sufficient data. Recurrences that occurred (mean 12.2 months) after completion of primary IVC included relapse of retinal tumor (143 eyes [48%]), vitreous seeding (73 eyes [25%]), subretinal seeding (49 eyes [16%]), or any combination (103 eyes [35%]). Out of 73 eyes with vitreous seeding, additional 66 eyes (90%) would have been salvaged with iVitc, potentially improving ocular survival rates to 71% (500 + 66/797). Conclusions: Evolving practice patterns of RB treatment have unfavorably skewed published ocular survival rates following IVC. With incorporation of iVitc, the ocular survival rates with IVC can be potentially improved to be non-inferior to those achieved with intra-arterial chemotherapy.

Intraocular tumors are primarily diagnosed clinically. However, ancillary tests such as fluorescein angiogram provides excellent visualization of retinal tumors while indocyanine green angiography reveals intrinsic vascular patterns of choroidal tumors. In this review, we contrast angiographic patterns of a variety of retinal, choroidal, and iris tumors.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

Purpose Sebaceous carcinoma can be highly malignant and difficult to treat. Surgical excision followed by periocular reconstruction is the primary method of treatment. In aggressive cases, radiation, topical chemotherapy, and systemic chemotherapy have been explored as adjuvant therapy. Immunotherapy, through immune checkpoint inhibitors, has proven to have significant antitumor effect in many cancer types, including melanoma, non-small cell lung cancer, renal cell carcinoma, and cutaneous squamous cell carcinoma. Little is known about endogenous immune response directed against sebaceous carcinoma. In this study, we aim to characterize the expression pattern of PD-1 and its ligands PD-L1 and PD-L2 in both sebaceous carcinoma and in infiltrating immune cells to explore the potential use of checkpoint blockade as therapy. Methods We performed a retrospective chart and histology review of patients with sebaceous carcinoma between 1990 and 2017 at the University of Wisconsin. Tissue microarrays were made from paraffin blocks. Immunohistochemistry was performed for evaluation of tumor and immune cell infiltration for expression of PD-1, PD-L1, and PD-L2. Tumor or infiltrating immune cells were considered positive if ≥5% of cells had membranous (cell surface) expression. Results Twenty-eight patients were included. PD-L1 and PD-1 were not significantly expressed on tumor cells; however, PD-L1 and PD-1 were expressed on infiltrating immune cells in 46% and 25% of patients, respectively. In contrast, PD-L2 demonstrated positive expression on tumor cells in 46% of the cases along with positive expression on infiltrating immune cells in 38% of the cases. Conclusions Sebaceous carcinoma currently has few effective adjuvant treatment options. The expression of PD-1, PD-L1, and PD-L2 on infiltrating immune cells and PD-L2 on tumor cells restrains T-cells from full activation and proliferation, therefore limiting the antitumor effect of T-cells, tipping the balance toward unopposed tumor progression. Consequently, PD-1 or PD-L1 inhibitors may have a role in sebaceous carcinoma treatment. Given the prevalence of PD-L2 expression in sebaceous carcinoma and the lack of PD-L2 blockade therapy available, PD-1 blockade may provide benefit over PD-L1 inhibitors. PD-1 blockade in combination with current methods may be a viable therapeutic option for patients with sebaceous carcinoma and deserves further study.Sebaceous carcinoma of the ocular and periocular regions showed expression of immune checkpoint ligands PD-1, PD-L1, and PD-L2, which suggests PD blockade may provide benefit as an adjuvant therapy for patients with sebaceous carcinoma.

Purpose: This study aimed to explore factors for refusing treatment in patients diagnosed with uveal melanoma and their subsequent clinical course. Methods: This study included patients with uveal melanoma who refused standard of care treatment. Patient-reported reasons and pre-existing mental health diagnoses were assessed. The sociodemographic profile was compared with the controls. Ocular survival, metastasis-free survival (MFS), and overall survival (OS) were calculated. Results: Nine patients with uveal melanoma declined ocular treatment (plaque brachytherapy, n = 7 [78%]; enucleation, n = 2 [22%]). The choroidal melanomas were small (n = 1 [11%]), medium (n = 5 [56%]), and large (n = 3 [33%]) in size (COMS criteria). The sociodemographic profile of the study patients was not different from those that accepted treatment. One patient (11%) had pre-existing mental health diagnosis. Five patients (56%) eventually accepted treatment following an average delay of 19 months (range: 4–55 months) due to neovascular glaucoma or severe vision loss. MFS could not be ascertained, and OS was 67% (6/9) at 4.2 years of follow-up (mean). Conclusions: Refusal of initial recommended treatment is associated with poor ocular survival. The small sample size did not allow for an evaluation of the impact on survival.

Purpose To assess margins and the rate of local recurrence of ocular surface squamous neoplasia after excision with a 2 mm margin and cryotherapy at a single ophthalmic oncology center. Outcome measures (1) Conjunctival margin were assessed as positive, negative, or indeterminate margins. (2) Feasibility of repair without a graft. (3) Local recurrence. Methods Retrospective chart review of histologically proven conjunctival intraepithelial neoplasia and invasive squamous cell carcinoma cases that underwent excision with a 2 mm margin and cryotherapy. Results Eighty cases met inclusion criteria for the quantitative analysis. The margin was positive in six cases (7.5%), four of which were treated with post-op topical immunotherapy/chemotherapy. Of the six positive margin cases, there was one recurrence which occurred in the patient who did not receive post-op topical adjuvant therapy, however resolved after starting topical treatment. Conjunctival repair without use of a graft was feasible in 74 (93%) cases with a mean basal diameter of 6.4 mm. Total number of local recurrence was seen in three cases (4%), which were successfully treated with adjuvant topical treatment (one positive margin case, one indeterminate margin case) or repeat resection followed by episcleral plaque brachytherapy (one negative margin case). Conclusion Excision with 2 mm margin of OSSN is not associated with high rates of positive surgical margins. Even those with positive margins, when treated with adjuvant topical therapy did not develop recurrence. While achieving low rates of local recurrence, the conjunctiva is conserved, thereby minimizing the need for amniotic membrane or free conjunctival grafts for conjunctival repair.

The authors report a case of a diffuse choroidal hemangioma in the left eye of a 17-year-old girl. No evidence of leptomeningeal angiomatosis was found on magnetic resonance imaging and neither the medical history nor the clinical examination revealed a port wine birthmark on the left side of the face. Fine telangiectatic vessels were found on the bulbar conjunctiva of the ipsilateral eye. Because of the shared destination of the vessel-trigeminal-ectoderm complex that migrates toward the optic placode, forming choriocapillaris, upper facial skin (upper eyelid), and conjunctival vessels, an embryological basis can be offered for ophthalmic angiomatosis of Sturge-Weber syndrome. The authors propose that vascular angiomatosis of upper eyelid skin and conjunctiva are phenotypically equivalent and may be present or absent, independent of each other. Their proposed expansion of Sturge-Weber syndrome diagnostic criteria needs to be validated by a comprehensive review of ophthalmic features of Sturge-Weber syndrome. [ J Pediatr Ophthalmol Strabismus . 2020;57:e43–e47.]

AimTo assess the role of map biopsy in patients with conjunctival primary acquired melanosis (PAM)/melanoma.MethodsRetrospective case series of 400 conjunctival biopsy samples of 51 unique patients in a tertiary referral centre.ResultsEach patient underwent one diagnostic biopsy and several additional map biopsies (range 2–7) providing a total of 400 samples for the analysis (55 diagnostic biopsies, 345 map biopsies). The median age was 63 years old (range 20–88) with women representing 67% of the cases. Histopathological findings were graded as negative for melanosis/normal (grade 0), melanosis without atypia (grade 1), melanosis with mild atypia (grade 2), melanosis with severe atypia (grade 3) or invasive melanoma (grade 4). Clinicopathologic concordance was observed in the majority of the map biopsies (313, 91%) (positive: clinical+/path+ (57,17%), negative: clinical−/path− (256, 74%)). Three discordant samples (clinical−/path+) represented PAM sine pigmento. The histopathological spectrum of atypia was absent (40, 73%) or limited (11, 20%) in the majority of cases with tendency to cluster as low-grade or high-grade atypia. Map biopsy led to the identification of six patients (11%) with severe atypia, requiring topical mitomycin (MMC). Similarly, in 29 cases, periodic observation without topical MMC was recommended. One case of invasive melanoma transformation occurred in the MMC-treated group.ConclusionsMap biopsy enhances overall assessment of the anatomic and pathologic extent, impacting use of adjuvant topical chemotherapy. In absence of map biopsy, it would be impossible to diagnose PAM sine pigmento. Additional corroborative work is needed to validate our observations.

To determine the response rate of choroidal melanoma following primary photodynamic therapy, we conducted a meta-analysis of published studies. A total of 7 studies reporting photodynamic therapy as primary treatment of choroidal melanoma in 162 patients with a mean tumor height of 2.8 mm (1.4 to 4.2) were identified. Forty-six percent of tumors were amelanotic, 48% were fully pigmented, and 6% had partial pigmentation. The photodynamic therapy parameters in all studies included 10-minute intravenous infusion of verteporfin (6 mg/m2), but varied in number of sessions (1 to 3), fluence (1× to 19×), and number of spots (single or multiple). The response was defined as tumor regression (partial or total) or lack of growth after initial treatment. The response to photodynamic therapy was predominantly observed as regression (126 [78%]). Overall response rate was 80% (mean) with a wide range among studies (58%–100%) over a period of 50 months (mean) with variable follow-up (range, 1–156 months). None of the studies reported progression- or recurrence-free survival; however, the recurrence rate was not related to the follow-up duration. Favorable prognostic factors were smaller size and lack of pigmentation. The overall response rate of 80% suggests that photodynamic therapy may be an effective primary treatment for small choroidal melanoma, especially in cases without pigmentation. Artifacts in study design (inclusion criteria and outcome measure) may have contributed to the variable observed response rate. Further studies with uniform inclusion criteria, standardized treatment parameters, well-defined outcome measures, and long follow-up are needed.

Eye pain is a common complaint, but no previous studies have determined the most common causes of this presenting symptom. Our objective was to determine the most common causes of eye pain in 2 ophthalmology and neurology departments at academic medical centers.This was a retrospective cross-sectional analysis and chart review at the departments of ophthalmology and neurology at the University Hospital Zurich (USZ), University of Zürich, Switzerland, and the University of Utah (UU), USA. Data were analyzed from January 2012 to December 2013. We included patients aged 18 years or older presenting with eye pain as a major complaint.Two thousand six hundred three patient charts met inclusion criteria; 742 were included from USZ and 1,861 were included from UU. Of these, 2,407 had been seen in an ophthalmology clinic and 196 had been seen in a neurology clinic. Inflammatory eye disease (conjunctivitis, blepharitis, keratitis, uveitis, dry eye, chalazion, and scleritis) was the underlying cause of eye pain in 1,801 (69.1%) of all patients analyzed. Although only 71 (3%) of 2,407 patients had migraine diagnosed in an ophthalmology clinic as the cause of eye pain, migraine was the predominant cause of eye pain in the neurology clinics (100/196; 51%). Other causes of eye pain in the neurology clinics included optic neuritis (44 patients), trigeminal neuralgia, and other cranial nerve disorders (8 patients).Eye pain may be associated with a number of different causes, some benign and others sight- or life-threatening. Because patients with eye pain may present to either a neurology or an ophthalmology clinic and because the causes of eye pain may be primarily ophthalmic or neurologic, the diagnosis and management of these patients often requires collaboration and consultation between the 2 specialties.

BackgroundCurrent practice methods are unclear as to the most safe and effective prophylactic pharmacotherapy and method of delivery to reduce postoperative endophthalmitis occurrence.MethodsA systematic review and meta-analysis using Meta-analysis of Observational Studies in Epidemiology guidelines was performed to compare the efficacy of intracameral cefuroxime, moxifloxacin and vancomycin in preventing postphacoemulsification cataract surgery endophthalmitis. A safety analysis of intracameral antibiotics was concurrently performed.Data sourcesBIOSIS Previews, CINAHL, ClinicalTrials.gov, Cochrane Library, Dissertations & Theses, EMBASE, PubMed, ScienceDirect and Scopus were searched from inception to January 2017. Data were pooled using a random effects model. All articles were individually reviewed and data were extracted by two independent reviewers. Funnel plot, risk of bias and quality of evidence analyses were performed.ResultsSeventeen studies with over 900 000 eyes were included, which favoured the use of intracameral antibiotics at the end of cataract surgery (OR 0.20; 95% CI 0.13 to 0.32; P0.3). Most studies had low to moderate risk of bias. The safety analysis showed minimal toxicity for moxifloxacin. Dosing errors led to the majority of toxicities with cefuroxime. Although rare, vancomycin was associated with toxic retinal events.ConclusionIntracameral cefuroxime and moxifloxacin reduced endophthalmitis rates compared with controls with minimal or no toxicity events at standard doses. Additionally, intracameral antibiotics alone may be as effective as intracameral plus topical antibiotics.

Purpose: This interventional case report discusses inadvertent bilateral temporal globe penetration during placement of intramuscular wire electrodes to the lateral rectus muscles for intraoperative neurophysiological monitoring (IONM) via electromyography. Methods: An 11-year-old girl underwent surgical resection of massive medulloblastoma within the fourth ventricle, requiring IONM. Placement of an electrode in each lateral rectus muscle resulted in bilateral globe penetration, with choroidal rupture, retinal tears, and hemorrhage. Results: Sterile needle perforation of the globe did not result in endophthalmitis. Encircling laser retinopexy was performed, and no retinal detachments occurred. Conclusions: Insertion of needle electrodes without guidance imaging can potentially lead to globe penetration and incorrect electrode placement. Direct visualization with ultrasound, electromyography, or other advanced image-guided systems may offer a safe solution for electrode placement to avoid injury. Verbal patients should be made aware of postoperative warning signs of globe penetration. For nonverbal patients, a postoperative dilated exam is warranted.

// Randy C. Bowen 1 , Nancy Ann B. Little 1 , Joshua R. Harmer 1 , Junjie Ma 2 , Luke G. Mirabelli 1 , Kyle D. Roller 1 , Andrew Mackay Breivik 1 , Emily Signor 1 , Alec B. Miller 1 and Hung T. Khong 1 1 Department of Oncology, University of Utah, Salt Lake City, Utah, USA 2 Department of Pharmacotherapy, University of Utah, Salt Lake City, Utah, USA Correspondence to: Hung T. Khong, email: // Keywords : neutrophil-to-lymphocyte ratio, gastrointestinal cancers, prognostic indicator, overall survival, biomarkers Received : August 19, 2016 Accepted : February 20, 2017 Published : March 16, 2017 Abstract An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines. Included were randomized control trials and observational studies that analyzed humans with gastrointestinal cancers that included NLR and hazard ratios (HR) with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and/or cancer-specific survival (CSS). We analyzed 144 studies comprising 45,905 patients, two-thirds of which were published after 2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate models were 3.4, 3.0, 5.0 (±IQR 2.5-5.0), respectively. Overall, NLR greater than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P < 0.001). This association was observed in all subgroups based on tumor site, stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70 (95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83 (95% CI, 1.50-2.23, P < 0.001), respectively. Available evidence suggests that NLR greater than the cutoff reduces OS, independent of geographic location, gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS also have worse outcomes with elevated NLR.

Minimal clinically important differences (MCIDs) for the American Shoulder and Elbow Surgeons (ASES) score, the Simple Shoulder Test (SST), and a visual analog scale (VAS) measuring pain have not been previously described using an anchor-based method after shoulder arthroplasty. The purpose of this study was to determine the MCIDs for these measures after shoulder arthroplasty for glenohumeral arthritis or advanced rotator cuff disease.Primary anatomic total shoulder arthroplasty (TSA), primary reverse TSA, or hemiarthroplasty was performed in 326 patients by 1 of 5 shoulder and elbow surgeons. The SST score, ASES score, and VAS pain score were collected preoperatively and at a minimum of 2 years postoperatively (mean, 3.5 years). The MCIDs were calculated for the ASES score, SST score, and VAS pain score using an anchor-based method.The MCIDs for the ASES score, SST score, and VAS pain score were 20.9 (P .001), 2.4 (P .0001), and 1.4 (P = .0158), respectively. Duration of follow-up and type of arthroplasty (anatomic TSA vs reverse TSA) did not have a significant effect on the MCIDs (P .1) except shorter follow-up correlated with a larger MCID for the ASES score (P = .0081). Younger age correlated with larger MCIDs for all scores (P .024). Female sex correlated with larger MCIDs for the VAS pain score (P = .123) and ASES score (P = .05).Patients treated with a shoulder arthroplasty require a 1.4-point improvement in the VAS pain score, a 2.4-point improvement in the SST score, and a 21-point improvement in the ASES score to achieve a minimal clinical importance difference from the procedure.

// Adam L. Cohen 1, * , Abhijit Ray 2, * , Matthew Van Brocklin 3 , David M. Burnett 3 , Randy C. Bowen 4 , Donna L. Dyess 5 , Thomas W. Butler 5 , Theresa Dumlao 6 and Hung T. Khong 1 1 Department of Medicine, Division of Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA 2 Division of Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA 3 Department of Surgery, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA 4 Department of Medicine, University of Utah, Salt Lake City, UT, USA 5 University of South Alabama, Mitchell Cancer Institute, Mobile, AL, USA 6 Banner MD Anderson Cancer Center, Gilbert, AZ, USA * These authors have contributed equally to this work Correspondence to: Hung T. Khong, email: hung.khong@hci.utah.edu Keywords: nab-paclitaxel, azacitidine, solid tumor, phase I clinical trials, SPARC Received: August 19, 2016 Accepted: November 18, 2016 Published: December 26, 2016 ABSTRACT Background: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel. Methods: Patients received escalating azacytidine doses daily for 5 days, followed by nab-paclitaxel at the standard 100mg/m2 weekly dose for 3 weeks in 4-week cycles. Dose-limiting toxicities (DLTs) were monitored during the first cycle. Serum was obtained at baseline, during and after treatment for correlative study. Results: All sixteen total patients enrolled were evaluable for toxicity, while 13 patients were evaluable for response. Two of five patients treated with 100mg/m2 of azacytidine had DLT of prolonged grade 4 neutropenia. Therefore, the MTD of azacitidine in this regimen is 75 mg/m 2 . Three additional patients were treated with no grade 4 toxicity in cycle 1. Clinical activity included 1 complete response (CR) in refractory DLBCL, 2 CR in ovarian cancer, 4 partial responses (PR) in ovarian and endometrial cancer, 4 stable diseases (SD) in lung, sarcoma and pancreatic cancer, 1 unconfirmed PR in breast cancer, and 1 progression of disease in CLL/SLL. Conclusions: Priming with azacitidine 75 mg/m 2 daily for 5 days, followed by weekly nab-paclitaxel 100 mg/m 2 weekly was well tolerated and results in dramatic responses pre-treated cancer patients.

Introduction Clinic based uroflowmetry is commonly used in the diagnosis and management of lower urinary tract symptoms. AUA (American Urological Association) guidelines recommend 2 separate uroflowmetry tests with a voided volume greater than 150 ml for accurate interpretation. We characterized the interpretability of a series of uroflowmetry tests done at our institution and hypothesized that a significant number were noninterpretable because of inadequate urine volume. Methods Uroflowmetry results were collected from male patients at the UH (University of Utah Hospital) and VAMC (George Wahlen Veterans Affairs Medical Center) urology clinics between August 31, 2014 and September 30, 2014. Average time to perform uroflowmetry was determined. Tests with a volume of 150 ml or less were classified as noninterpretable. Data were characterized using descriptive statistics. Results During the study period 169 tests were collected, including 104 at UH and 65 at VAMC, of which 107 (63%) were noninterpretable. An estimated total of 1,452 tests were performed at UH and VAMC within a 12-month period. Average time to perform uroflowmetry by health care workers was 2 minutes 18 seconds. The estimated time loss per year for medical personnel due to noninterpretable uroflow studies was 35 hours. Conclusions More than 50% of clinic based uroflowmetry tests at our institution had a voided volume of 150 ml or less and were deemed noninterpretable per AUA guidelines. Current clinic based uroflowmetry testing strategies are inefficient and wasteful. Reliable, accurate alternatives to clinic based uroflowmetry for the diagnosis and management of lower urinary tract symptoms should be explored.

Pediatric oncology patients often experience fatigue and physical and mental deconditioning during and following chemotherapy treatments, contributing to diminished quality of life. Patient empowerment is a core principle of patient-centered care and reflects one's ability to positively affect his or her own health behavior and health status. Empowerment interventions may enhance patients' internal locus of control, resilience, coping skills, and self-management of symptoms related to disease and therapy. Clinical and technological advancements in therapeutic videogames and mobile medical applications (mobile health) can facilitate delivery of the empowerment interventions for medical purposes. This review summarizes clinical strategies for empowering pediatric cancer patients, as well as their relationship with developing a “fighting spirit” in physical and mental health. To better understand physiological aspects of empowerment and to elucidate videogame-based intervention strategies, brain neuronal circuits and neurotransmitters during stress, fear, and resilience are also discussed. Neuroimaging studies point to the role of the reward system pathways in resilience and empowerment in patients. Taken together, videogames and mobile health applications open translational research opportunities to develop and deliver empowerment interventions to pediatric cancer patients and also to those with other chronic diseases.

Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products, and their integration with self-care, music and mHealth, expands precision/personalized medicine strategies for chronic diseases via pharmacological-behavioral combination therapies.

Background The Patient Acceptable Symptom State (PASS) is a symptom state that a patient considers acceptable. No prior study has determined the PASS for the American Shoulder and Elbow Surgeons (ASES) score, the Simple Shoulder Test (SST), and the Visual Analog Scale (VAS) pain score after shoulder arthroplasty. The purpose of this study was to determine the PASS for the ASES score, the SST score, and VAS pain for patients treated with a total shoulder arthroplasty. Methods A total of 326 patients had a primary anatomic total shoulder arthroplasty (TSA) or primary reverse total shoulder arthroplasty (RSA) by 1 of 5 shoulder and elbow surgeons at 1 of 2 institutions. Each patient completed the SST, ASES score, and a VAS pain preoperatively and at a minimum of 2 years postoperative (average 3.5 years). The PASS value for the ASES score, SST, and VAS pain was calculated. Results The PASS for the ASES score, SST, and VAS pain was 76, 8.4, and 1.5, respectively. Neither hand dominance nor age had a significant effect on PASS for SST, VAS, and ASES ( P > .05). Gender had significant effect on SST and ASES scores with P -values of

3018 Background: Intratumoral (IT) IL-2 is highly effective and well tolerated, but does not generate systemic immunity or response in untreated lesions. Intravenous (IV) ipilimumab (Ipi) lowers th...