Influence of life history variation and habitat on mercury bioaccumulation in a high-order predatory fish in tropical Australia.

Mercury distribution and bioaccumulation in aquatic ecosystems of tropical Australia is poorly characterised. Barramundi (Lates calcarifer), a widespread high-order predator in both fresh and coastal marine waters of the region, fulfils requirements for a bio-indicator of mercury contamination. In a study of the Mary River system of the Northern Territory, total mercury in the muscle tissue of 300 specimens gathered over four years (2013-2017, across both wet and dry seasons) was determined by direct combustion-atomic absorption spectrometry. Source of nutrition and trophic position of barramundi in the food web was also estimated via carbon and nitrogen isotopes (δ13C and δ15N), respectively, in tissue by stable isotope mass spectrometry, and determination of strontium isotopes (87Sr/86Sr) in otoliths by laser ablation-ICPMS differentiated between freshwater and saltwater residence. Results showed that fish moving into freshwater floodplain wetlands concentrated mercury in muscle tissue at approximately twice the level of those that remained in saline habitats. Resolving life histories through otolith analyses demonstrated diversity in mercury bioaccumulation for individual fish of the same migratory contingent on the floodplains. Although trophic level (δ15N), capture location, source of nutrition (δ13C), and age or size partly predicted mercury concentrations in barramundi, our results suggest that individual variability in diets, migration patterns and potentially metabolism are also influential. Using a migratory fish as a bio-indicator, and tracking its life history and use of resources, proved valuable as a tool to discern hot spots in a coastal waterway for a contaminant, such as mercury.

Clinical presentation, national practice patterns, and outcomes of breast adenomyoepithelioma.

Breast adenomyoepithelioma (AME) is a rare tumor with the published literature mainly in the form of case reports. Thus, there is currently only limited published data to guide evidence-based management. We sought to use a large, contemporary US database to evaluate how these patients are managed and describe expected outcomes. The National Cancer Database was queried (2004-2013) for women with AME. Statistics included multivariable logistic regression, Kaplan-Meier analysis to evaluate overall survival (OS) and Cox proportional hazards modeling. Overall, 110 patients were analyzed. At diagnosis, the median age was 67 years and the median tumor size was 2.0 cm. All but four patients had node-negative disease. A majority (55%) of tumors were estrogen receptor negative, and only one was positive for HER2/neu. The most common surgical procedure was lumpectomy (60%); a minority (10.9%) of subjects underwent complete axillary nodal dissection, with one-quarter not undergoing pathologic nodal sampling. Chemotherapy, hormonal therapy, and radiotherapy were utilized in a minority of patients (26%, 8%, and 36%, respectively), and none were associated with OS. At median follow-up of 52 months, the 5-year OS for the entire population was 74.4%. Disease-related characteristics and practice patterns are described for AME, the largest study of this rare tumor to date. Resection is the most important aspect of management, and based on this dataset the low rate of nodal involvement suggests that in some cases nodal sampling could be safely omitted. Adjuvant therapy may be considered on a case-by-case basis. Taken together, these data provide valuable insight into a rare neoplasm that may better inform management of these patients.

Omission of radiation therapy following breast conservation in older (≥70 years) women with T1-2N0 triple-negative breast cancer.

BACKGROUND: Although randomized data support omitting adjuvant radiotherapy (RT) following breast conservation for T1-2N0 estrogen receptor positive breast cancer in ≥70-year-old women, there remains a knowledge gap regarding its omission for triple-negative BC (TNBC). METHODS AND MATERIALS: The National Cancer Database (NCDB) was queried for ≥70-year-old females with newly diagnosed T1-2N0M0 TNBC treated with breast conservation. Multivariable logistic regression ascertained factors associated with adjuvant RT administration. Overall survival (OS) between patients treated with or without adjuvant RT was estimated using the Kaplan-Meier method. Cox proportional hazards modeling determined variables associated with OS. RESULTS: Of 8526 patients, 6283 (74%) patients received adjuvant RT, and 2243 (26%) did not. RT was more frequently withheld in older patients, those with higher comorbidities, lower income, pT2 disease, following margin-positive resection, receipt of chemotherapy, and at academic centers (P < 0.05 for all). Median follow-up was 38.0 months. Five-year OS was greater in the adjuvant RT group (77.2% vs 55.3%, P < 0.001); these differences persisted when stratifying for age, T stage, and chemotherapy utilization (P < 0.001 for all). Omission of RT was also independently associated with poorer OS on multivariate analysis (P < 0.001). CONCLUSIONS: This investigation, the largest known such study to date, observed that omission of adjuvant RT for elderly women with T1-2N0 TNBC was associated with poorer OS; this was observed across a range of age groups, as well as following stratification by T stage and chemotherapy usage. Although these results do not imply causation, caution must be exercised when considering omission of adjuvant RT in node-negative TNBC patients.

Biopsy proven metastatic meningioma: A case report and review of the literature.

Meningiomas are the most common type of benign tumor found in the brain and are typically benign, slow-growing lesions. The current standard of care consists of surgical resection and subsequent postoperative radiotherapy to prevent local recurrence. Because of their indolent nature, meningiomas are rarely found to spread extracranially and develop distant metastases. We present the clinical, imaging, and pathologic features of a patient who had meningioma with multiple local recurrences, who was incidentally found to have metastatic disease in the lungs. In addition, we discuss details of this case in the context of the previously reported literature.

Utilization of radiotherapy and stereotactic body radiation therapy for renal cell cancer in the USA.

AIM: This study evaluated national practice patterns of cT1N0M0 renal cell cancer, with a focus on stereotactic body radiation therapy (SBRT) utilization. METHODS: The National Cancer Database was queried (2004-2013) for patients with newly-diagnosed cT1a/bN0M0 renal cell cancer that received definitive treatment. Temporal trends in utilization were tabulated. RESULTS: Altogether, 138,495 patients met inclusion criteria; 13,725 (9.9%) patients received ablative therapy, 57,924 (41.8%) partial nephrectomy, 67,168 (48.5%) radical nephrectomy and 308 (0.2%) external beam radiation therapy (EBRT). The proportion of EBRT that was SBRT increased substantially from 25% in 2004 to 95.4% in 2013, with a sharp inflection point from 2005 to 2006. CONCLUSION: SBRT utilization has sharply risen over time; in most recent years, the vast majority of EBRT is delivered in the form of SBRT.

A novel integrative procedure for identifying and integrating three-dimensions of objectively measured free-living sedentary behaviour.

BACKGROUND: The widely accepted definition of sedentary behaviour [SB] refers to any waking behaviour characterized by an energy expenditure ≤1.5 metabolic equivalents [METs] while in a sitting or reclining posture. At present, there is no single field-based device which objectively measures sleep, posture and activity intensity simultaneously. The aim of this study was to develop a novel integrative procedure [INT] to combine information from two validated activity monitors on sleep, activity intensity and posture, the three key dimensions of SB. METHODS: Participants in this analysis were initially recruited from a series of three studies conducted between December 2014 and June 2016 at the University of Leeds. Sixty-three female participants aged 37.1 (13.6) years with a body mass index of 29.6 (4.7) kg/m2 were continuously monitored for 5-7 days with the SenseWear Armband [SWA] (sleep and activity intensity) and the activPAL [AP] (posture). Data from both activity monitors were analysed separately and integrated resulting in three measures of sedentary time. Differences in Sedentary time between the three measurement methods were assessed as well as how well the three measures correlated. RESULTS: The three measures of sedentary time were positively correlated, with the weakest relationship between SEDSWA (awake and <1.5 METs) and SEDAP (awake and sitting/lying posture) [r(61) = .37,p = .003], followed by SEDSWA and SEDINT (awake, <1.5 METs and sitting/lying posture) [r(61) = .58,p < .001], and the strongest relationship was between SEDAP and SEDINT [r(61) = .91,p < .001]. There was a significant difference between the three measures of sedentary time [F(1.18,73.15) = 104.70,p < .001]. Post-hoc tests revealed all three methods differed significantly from each other [p < .001]. SEDSWA resulted in the most sedentary time 11.74 (1.60) hours/day, followed by SEDAP 10.16 (1.75) hours/day, and SEDINT 9.10 (1.67) hours/day. Weekday and weekend day sedentary time did not differ for any of the measurement methods [p = .04-.25]. CONCLUSION: Information from two validated activity monitors was combined to obtain an objective measure of free-living SB based on posture and activity intensity during waking hours. The amount of sedentary time accumulated varied according to the definition of SB and its measurement. The novel data integration and processing procedures presented in this paper represents an opportunity to investigate whether different components of SB are differentially related to health end points.

Saccharides enhance iron bioavailability to Southern Ocean phytoplankton.

Iron limits primary productivity in vast regions of the ocean. Given that marine phytoplankton contribute up to 40% of global biological carbon fixation, it is important to understand what parameters control the availability of iron (iron bioavailability) to these organisms. Most studies on iron bioavailability have focused on the role of siderophores; however, eukaryotic phytoplankton do not produce or release siderophores. Here, we report on the pivotal role of saccharides--which may act like an organic ligand--in enhancing iron bioavailability to a Southern Ocean cultured diatom, a prymnesiophyte, as well as to natural populations of eukaryotic phytoplankton. Addition of a monosaccharide (>2 nM of glucuronic acid, GLU) to natural planktonic assemblages from both the polar front and subantarctic zones resulted in an increase in iron bioavailability for eukaryotic phytoplankton, relative to bacterioplankton. The enhanced iron bioavailability observed for several groups of eukaryotic phytoplankton (i.e., cultured and natural populations) using three saccharides, suggests it is a common phenomenon. Increased iron bioavailability resulted from the combination of saccharides forming highly bioavailable organic associations with iron and increasing iron solubility, mainly as colloidal iron. As saccharides are ubiquitous, present at nanomolar to micromolar concentrations, and produced by biota in surface waters, they also satisfy the prerequisites to be important constituents of the poorly defined "ligand soup," known to weakly bind iron. Our findings point to an additional type of organic ligand, controlling iron bioavailability to eukaryotic phytoplankton--a key unknown in iron biogeochemistry.

Personalized Radiation Therapy for Breast Cancer.

Breast cancer is diagnosed in nearly 3 million people worldwide. Radiation therapy is an integral component of disease management for patients with breast cancer, and is used after breast-conserving surgery or a mastectomy to reduce the risk of a local recurrence. The following review describes the methods used to personalize radiation therapy by optimizing patient selection, using advanced treatment techniques to lessen the radiation dose to normal organs, and using hypofractionation in order to shorten the duration of radiation treatment.

Retrospective Analysis of Radiation-Induced Complications of Uveal Melanoma Patients Treated With Brachytherapy in the Era of Anti-VEGF.

PURPOSE: To associate clinical factors and radiation doses delivered by iodine-125 plaque brachytherapy to visual outcomes and development of radiation-induced ocular complications in patients with uveal melanoma in the era of anti-vascular endothelial growth factor (anti-VEGF) injections. DESIGN: Retrospective cohort study. METHODS: A retrospective chart review was performed for 225 patients treated with iodine-125 brachytherapy for uveal melanoma. The effects of radiation doses (focal doses, average dose to the entire eye, and integral dose) on visual outcomes and development of radiation complications (radiation retinopathy, radiation optic neuropathy, vitreous hemorrhage, and neovascular glaucoma) were analyzed using multivariate Cox regression snalysis. RESULTS: Median follow-up was 33.6 months (range, 12-105.6 months). Radiation retinopathy was associated with younger age, tumor distance to optic nerve <6 mm, and maximum radiation dose to fovea. Radiation optic neuropathy was associated with White race, tumor distance to optic nerve <6 mm, and integral radiation dose. Vitreous hemorrhage was associated with White race and integral radiation dose. Incidence of neovascular glaucoma was low in our study, with 2 patients (0.9%) developing the complication. Of the 123 patients who developed radiation retinopathy, 82 patients (66.7% of radiation retinopathy patients, 37.3% of total patients) received anti-VEGF injections. CONCLUSIONS: Our study found multiple associations between radiation doses and complications as well as visual outcomes on multivariate analysis. Given that the majority of our patients who developed radiation retinopathy received anti-VEGF injections, our study helps to illustrate the course and progression of radiation-induced complications in the new era of anti-VEGF.

Re-treatment of locally recurrent uveal melanoma with repeat eye plaque I-125 brachytherapy: A single institution experience.

PURPOSE: Eye plaque brachytherapy (EPBT) is the most common treatment for uveal melanoma with high local control rates of 95-100%. When local recurrences occur following EPBT, salvage options include enucleation, transpupillary thermotherapy (TTT), external beam radiation, or re-irradiation with EPBT. The purpose of this study is to report our institution's experience with EPBT re-irradiation for locally recurrent uveal melanoma. METHODS AND MATERIALS: Patients were included if they were previously treated for uveal melanoma with EPBT, experienced local recurrence, and were subsequently treated at our institution with EPBT from 2016- 2020. RESULTS: A total of 5 patients with median age 68 years were included. All patients were initially treated at an outside institution (OSI) with Iodine-125 or Ruthenium-106 EPBT. Mean time between EPBT at the OSI and EPBT at our facility was 130 months (range 28-231 months). Patients were re-irradiated with Iodine-125 EPBT prescribed to 85 Gy over 168 hours. Median follow up after re-treatment at our center was 24 months. Local control among this cohort was 100%. Metastasis occurred in two patients after re-treatment, at 8 months and 7 months. At last follow up, all treated lesions were decreased in size. Four patients experienced worsening visual acuity. Four patients developed cataracts, while two patients developed radiation retinopathy with cystoid macular edema requiring anti-VEGF injections. One patient developed radiation retinopathy but did not require injections. No patients required enucleation. CONCLUSIONS: Re-treatment of locally recurrent uveal melanomas with EPBT is a feasible alternative to enucleation with a high local control rate. Ocular toxicities have not been significant enough to require enucleation.

A Phase 2 Study of In Situ Oncolytic Virus Therapy and Stereotactic Body Radiation Therapy Followed by Pembrolizumab in Metastatic Non-Small Cell Lung Cancer.

PURPOSE: A phase 2 study of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy in metastatic non-small cell lung cancer (mNSCLC) followed by pembrolizumab (STOMP) was designed to explore the dual approach in enhancing single pembrolizumab with ADV/HSV-tk plus valacyclovir gene therapy and SBRT in mNSCLC. METHODS AND MATERIALS: STOMP is a single-arm, open-label phase 2 study. Patients with mNSCLC received intratumoral injections of ADV/HSV-tk (5 × 1011 vp) and SBRT (30 Gy in 5 fractions) followed by pembrolizumab 200 mg IV every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR) (complete response [CR] and partial response [PR]). Secondary endpoints included clinical benefit rate (CBR) (CR, PR and stable disease [SD]), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 28 patients were enrolled, of whom 27 were evaluated for response. The ORR was 33.3%, including 2 CR (7.4%) and 7 PR (25.9%). CBR was 70.4%. Six of eight (75.0%) patients who were immune checkpoint inhibitor (ICI) refractory derived clinical benefits. Responders had durable responses with median PFS, and OS not reached. The entire cohort had a median PFS of 7.4 months (95% CI, 5.1-9.6 months), and median OS of 18.1 months (95% CI, 15.4-20.9 months). The combination was well tolerated, with grade 3 or higher toxicity in 6 (21.4%) patients. CONCLUSIONS: The dual approach of in situ ADV/HSV-tk plus valacyclovir gene therapy and SBRT as a chemotherapy-sparing strategy to enhance the antitumor effect of pembrolizumab is a well-tolerated encouraging treatment in patients with mNSCLC.

Estuarine benthic habitats provide an important ecosystem service regulating the nitrogen cycle.

Globally, a key ecosystem service provided by sedimentary estuarine habitats is the regulation of nutrient cycles. The nitrogen (N) cycle is driven by complex biogeochemical transformations within these sediments-including nitrogen fixation, denitrification, assimilation and anaerobic ammonia oxidation-mediated by microorganisms. Evaluating ecosystem processes and their functional value is a knowledge gap for the wet-dry tropics and even more limited for macrotidal estuaries. The capacity of these important environments to withstand and assimilate increasing nitrogenous loads as a consequence of accelerating development pressures in tropical Australia is largely unknown. Because of the critical role nitrogen cycling plays in estuarine ecosystems, identifying important habitats that underpin N cycling, particularly denitrification known to mitigate anthropogenic N inputs, is important. Detailed benthic habitat mapping of the Darwin-Bynoe region of northern Australia has provided a rare opportunity to demarcate its key habitats, such as intertidal mudflats, seagrass, mangroves, reef and saltmarsh. Combined with new measurements of benthic nitrogen fluxes, it has been possible for the first time to map these processes and develop a simple integrated functional value for N cycling across key benthic habitats of a tropical macrotidal estuary. Maps generated in this process have provided broadscale identification of the functional importance of habitats with relevance to N removal processes. The role of intertidal sediments in denitrification has been highlighted. Furthermore, the study emphasises connectivity across benthic seascapes, where multiple services are likely to interact, in supporting overall function and ecosystem health. The distillation of composite processes in this mapping format allows resource managers and scientists to communicate outputs visually with a simple classification scheme which could be superimposed with additional data to support environmental assessment and management.

Focal versus whole gland salvage brachytherapy for recurrent prostate cancer in the prostate specific membrane antigen PET era: a narrative review.

BACKGROUND AND OBJECTIVE: Prostate cancer is the second most common cause of cancer in men worldwide. A significant proportion of patients will develop biochemical failure after definitive radiotherapy and an increasing number of local failures are now identifiable with prostate specific membrane antigen (PSMA) positron emission tomography and computerized tomography (PET/CT). Brachytherapy (BT) represents an excellent option for definitive local salvage treatment. Consensus guidelines for the delivery of salvage BT are heterogenous and limited. Herein, we report the results from a narrative review analyzing whole gland and partial gland BT salvage to help guide treatment recommendations. METHODS: The PubMed and MEDLINE databases were searched in October 2022 to identify studies analyzing BT salvage in patients with recurrent prostate cancer after definitive external beam radiation therapy (EBRT). 503 initial studies met search criteria. After title and abstract screening, 25 studies met inclusion criteria and full-text review was performed. Twenty studies were included for analysis. Reports included whole gland (n=13) and partial gland or focal (n=7) salvage BT. KEY CONTENT AND FINDINGS: The median 5-year biochemical failure free survival (BFFS) for men receiving whole gland BT salvage was 52%, which is comparable to 5-year recurrence-free survival (RFS) rates for other salvage treatment modalities (radical prostatectomy (RP) 54%, high-intensity focused ultrasound (HIFU) 53%, cryotherapy 50%). However, the median rate of severe genitourinary (GU) toxicity was lower (12%) compared to published rates for other treatment modalities (RP 21%, HIFU 23%, and cryotherapy 15%). Furthermore, patients receiving partial gland salvage BT had even lower median rates of grade 3 or higher GU toxicity (4% vs. 12%) and gastrointestinal (GI) toxicity (0% vs. 3%), with 3-year BFFS of 58%. Only two studies directly comparing BT whole versus partial gland salvage were identified with comprehensive literature search and neither provided specific comparison regarding prescription dose or dose constraints. CONCLUSIONS: This narrative review identified only two studies that directly compared whole versus partial gland BT salvage treatment. Neither report provided a specific comparison of recommendations for dosimetric technique or normal structure dose constraints. Therefore, this review highlights a significant gap in the existing literature and provides an important framework to guide radiation treatment (RT) recommendations for both whole gland and partial gland salvage BT in patients with recurrent prostate cancer.

Single-port transoral robotic surgery for a rare tonsil mass.

Squamous cell carcinoma predominates as the most common malignant lesion of the oropharynx with human papilloma virus-associated disease now predominant over tobacco-related oropharynx cancer. Other rare malignant pathologies can manifest as visible neoplasms in these anatomic sites with varying degrees of symptoms such as dysphagia, odynophagia, otalgia, aspiration, hemorrhage, weight loss and dyspnea. We present a case of a rarely encountered primary oropharyngeal sarcoma managed by single-port transoral robotic resection and a selective cervical lymph node dissection followed by adjuvant radiotherapy.

Prognostic impact of biologically equivalent dose in stereotactic body radiotherapy for renal cancer.

Purpose /Objectives Materials/Methods: The National Cancer Database (NCDB) was queried (2004-2017) for patients with RCC who did not have surgical resection but received definitive SBRT. Kaplan-Meier analysis with log-rank test was used to evaluate overall survival (OS). Univariable (UVA) and multivariable (MVA) analysis were conducted using cox proportional hazard models to determine prognostic factors for OS. Results: A total of 344 patients with median age 77 (IQR 70-85) were included in this study. Median BED3 was 180 Gy (IQR 126.03-233.97). Median OS was 90 months in the highest quartile compared to 36-52 months in the lower three quartiles (p < 0.01). On UVA, the highest BED3 quartile was a positive prognostic factor (HR 0.67, p < 0.01 CI 0.51-0.91) while age, tumor size, T-stage, metastasis, renal pelvis location, and transitional cell histology were negative factors. On MVA, the highest BED3 quartile was remained significant (HR 0.69, p = 0.02; CI 0.49-0.95) as a positive factor, while age, metastasis were negative factors. Conclusion: Higher BED may be associated with improved OS. Prospective investigation is needed to clearly define optimal BED for SBRT used to treat RCC.

The emergence of marine recreational drone fishing: Regional trends and emerging concerns.

Online evidence suggests that there has been an increase in interest of using unmanned aerial vehicles or drones during land-based marine recreational fishing. In the absence of reliable monitoring programs, this study used unconventional publicly available online monitoring methodologies to estimate the growing interest, global extent, catch composition and governance of this practice. Results indicated a 357% spike in interest during 2016 primarily in New Zealand, South Africa and Australia. From an ecological perspective, many species targeted by drone fishers are vulnerable to overexploitation, while released fishes may experience heightened stress and mortality. From a social perspective, the ethics of drone fishing are being increasingly questioned by many recreational anglers and we forecast the potential for increased conflict with other beach users. In terms of governance, no resource use legislation specifically directed at recreational drone fishing was found. These findings suggest that drone fishing warrants prioritised research and management consideration.

Neoadjuvant Chemotherapy for Metaplastic Breast Cancer: Response Rates, Management, and Outcomes.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) for breast cance has not been well studied for metaplastic breast cancer (MBC), a rare but aggressive type of breast cancer. MATERIALS AND METHODS: The National Cancer Database was queried (2004-2017) for females with cM0 MBC who received NAC and definitive surgery with a pathologic staging record. Statistics included Kaplan-Meier overall survival (OS) analysis, multivariable logistic regression, and Cox proportional hazards modeling. RESULTS: Of 903 MBC patients, 88 (9.8%) experienced a pathologic complete response (pCR). The vast majority of ypT0 cases were initially cT1-2. On multivariable logistic regression, cT1 disease was a single factor that was associated with pCR. The majority of patients with MBC undergoing pCR still underwent mastectomy (62.5%) and sentinel node biopsy (67.1%). Axillary dissection was more common in non-pCR cases (49.3% vs. 29.6%, P = .001). The 5 year OS difference amongst MBC patients between pCR vs. RCB1-3 was significant (93 vs. 63%, P < .001). There was no difference observed between MpBC with pCR and non-MpBC invasive ductal carcinoma (IDC) with pCR (93 vs. 93%), with pCR (P > .05 for all molecular subtypes). CONCLUSION: This study confirms that response rates of MBC to NAC are low, with pCR being relatively infrequent. However, early-stage MBC may be more likely to achieve pCR. These findings combined with emerging research on identifying favorable histopathologic subtypes of MBC may better elucidate subsets with higher proclivity for pCR, especially because these patients achieve satisfactory survival, comparable to that of IDC with pCR.

Potentiating Antitumor Efficacy Through Radiation and Sustained Intratumoral Delivery of Anti-CD40 and Anti-PDL1.

PURPOSE: Mounting evidence demonstrates that combining radiation therapy (RT) with immunotherapy can reduce tumor burden in a subset of patients. However, conventional systemic delivery of immunotherapeutics is often associated with significant adverse effects, which force treatment cessation. The aim of this study was to investigate a minimally invasive therapeutics delivery approach to improve clinical response while attenuating toxicity. METHODS AND MATERIALS: We used a nanofluidic drug-eluting seed (NDES) for sustained intratumoral delivery of combinational antibodies CD40 and PDL1. To enhance immune and tumor response, we combined the NDES intratumoral platform with RT to treat the 4T1 murine model of advanced triple negative breast cancer. We compared the efficacy of NDES against intraperitoneal administration, which mimics conventional systemic treatment. Tumor growth was recorded, and local and systemic immune responses were assessed via imaging mass cytometry and flow cytometry. Livers and lungs were histologically analyzed for evaluation of toxicity and metastasis, respectively. RESULTS: The combination of RT and sustained intratumoral immunotherapy delivery of CD40 and PDL1 via NDES (NDES CD40/PDL1) showed an increase in both local and systemic immune response. In combination with RT, NDES CD40/PDL1 achieved significant tumor burden reduction and liver inflammation mitigation compared with systemic treatment. Importantly, our treatment strategy boosted the abscopal effect toward attenuating lung metastatic burden. CONCLUSIONS: Overall, our study demonstrated superior efficacy of combination treatment with RT and sustained intratumoral immunotherapy via NDES, offering promise for improving therapeutic index and clinical response.

Development of a congestive heart failure protocol in a rehabilitation setting.

A number of patients in a rehabilitation setting were being transferred to acute-care facilities with a diagnosis of congestive heart failure (CHF). A transfer penalty was charged to the rehabilitation facility based on each patient's length of stay. A multidisciplinary team was assembled with physician support to address the problem. The team's goal was to develop a CHF protocol with guidelines that would allow for more frequent nursing assessments and reporting to physicians. The protocol interventions were initiated consistently and monitored on each shift. These interventions allowed for more timely assessment and treatment of patients with signs and symptoms of CHF. As a result, the number of patients being transferred to acute-care hospitals has decreased, allowing patients to complete their rehabilitation process without interruption. The decreased number of patients being transferred to the acute-care setting has resulted in fewer transfer penalties for the rehabilitation facility.

Racial and Socioeconomic Disparities in the Delivery of Immunotherapy for Metastatic Melanoma in the United States.

Immunotherapy for metastatic melanoma has rapidly expanded, but racial and/or socioeconomic factors often impact the type of therapies delivered for cancer care. This study addressed a crucial public health priority by evaluating disparities in administration of immunotherapy for metastatic melanoma. The National Cancer Database was queried for newly diagnosed metastatic melanoma. Patients were dichotomized based on receipt of immunotherapy based on National Cancer Database coding. Multivariable logistic regression ascertained factors associated with immunotherapy delivery. Subgroup analysis evaluated the interaction between race, insurance status, and income. Secondarily, Cox multivariate and propensity-matched Kaplan-Meier analyses assessed overall survival based on immunotherapy receipt. Of 15,941 patients meeting the selection criteria, 2448 (15.4%) received immunotherapy, and 13,493 (84.6%) did not. Temporal trends showed that utilization of immunotherapy was 8%-12% of patients between 2004 and 2010, with utilization increasing to 29.7% of patients in 2014. Immunotherapy was more likely administered to younger and healthier patients, at academic centers, and in the absence of chemotherapy and brain metastases (P<0.05 for all). African Americans, along with patients with Medicaid and lower incomes were less likely to receive immunotherapy (P<0.05 for all). As expected, immunotherapy was associated with improved overall survival (median 16.3 vs. 8.3 mo, P<0.001). Although immunotherapy for metastatic melanoma is markedly escalating, not all populations experience this rise equally. Because immunotherapy utilization is expected to amplify even further in the future, these public health and economic issues are essential to identify and address appropriately, and have implications on public health policy, pharmaceutical and insurance companies, and value-based oncology. Methods to address these inequalities are also discussed.