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Background: Angiosarcomas are rare tumors that can be difficult to diagnose due to subtle changes in the vascular endothelium. When there is evidence to suggest malignancy, such as a pathologic fracture, further investigation is needed, and a high suspicion for angiosarcoma needs to be present so that appropriate immunohistochemical stains are utilized on biopsied tissue. In situations where such suspicion is high and prior biopsies have been negative, performance of splenectomy, can be both diagnostic and therapeutic when splenomegaly is present. Case Report: This is a case of a 52-year-old woman with splenomegaly, initially attributed to infection, in the setting of upper respiratory symptoms and thrombocytopenia. Three months later, however, she presented with back pain. Imaging showed lytic bone lesions with pathologic vertebral fracture and numerous liver lesions that were too small to characterize further. Initial biopsies of the liver and bone did not reveal a pathologic process. Several months later, still without a unifying diagnosis, she presented to our institution. MRI of the brain was done for neurologic concerns and showed pathologic enhancement in the calvarium. A PET scan showed diffuse avidity of the skeleton and spleen. After discussing the case with a hematologist, splenectomy was performed for both diagnostic and therapeutic purposes. Angiosarcoma was identified in the spleen and in a PET-directed bone biopsy. With a definitive diagnosis, she returned home and subsequently elected to pursue hospice care. Conclusion: When there is a high clinical suspicion for malignant angiosarcoma, a multidisciplinary approach is necessary to direct both tissue acquisition and necessary histochemical staining.

Recently, the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ. This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant (Pluronic F127), bioactive glass (BG), and black phosphorus (BP). The nanocomposite was prepared through a two-step synthetic strategy, including a microwave treatment that turned BP nanosheets (BPNS) into quantum dots (BPQDs) with 5 ± 2 nm dimensions in situ. The effects of surfactant and microwave treatment were assessed in vitro: the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite. The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid. The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro, finding that 150 μg mL−1 was the lowest concentration which prevented the proliferation of SAOS-2 cells, while the counterpart without BP did not affect the cell growth rate. Moreover, the apoptosis pathways were evaluated and a mechanism of action was proposed. NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia. The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer, breast cancer, and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers. The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells; the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells. This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.

Background: Nature-based and other outdoor virtual reality (VR) experiences in head-mounted displays (HMDs) offer powerful, non-pharmacological tools for hospice teams to help patients undergoing end-of-life (EOL) transitions. However, the psychological distress of the patient-caregiver dyad is interconnected and highlights the interdependence and responsiveness to distress as a unit. Hospice care services and healthcare need strategies to help patients and informal caregivers with EOL transitions. Methods: Our study uses the synchronized Tandem VR TM approach where patient-caregiver dyads experience immersive nature-based and other outdoor VR content. This mixed methods study will recruit 20 patient-caregiver dyads (N = 40) enrolled in home hospice services nearing EOL. Dyads will experience a personalized nature-based and other outdoor VR experience lasting 5–15 min. Self-reported questionnaires and semi-structured interviews will be collected pre/post the VR intervention to identify the impacts of Tandem VR TM experiences on the QOL, pain, and fear of death in patient-caregiver dyads enrolled with hospice services. Additionally, this protocol will determine the acceptance of Tandem VR TM experiences by dyads as a non-pharmacological modality for addressing patient and caregiver needs. Acceptance will be quantified by the number of dyads accepting or declining the VR experience during recruitment. Discussion: Using personalized, nature-based and other outdoor VR content, the patient-caregiver dyads can simultaneously engage in an immersive encounter may help alleviate symptoms associated with declining health and EOL phases for the patient and the often overburdened caregiver. This protocol focuses on meeting the need for person-centered, non-pharmacological interventions to reduce physical, psychological, and spiritual distress. Trial registration: NCT06186960.

Odour annoyance in urban contexts is of particular concerns and requires effective monitoring in order to avoid complaints from citizens.The research presents an advanced and integrated odour monitoring system, which combines analytical, senso-instrumental and citizen science tools, for the continuous and proactive characterization of the odours in ambient air to prevent odour annoyance. The on-site validation of the system was implemented integrating data collected by IOMSs and air quality station with 768 reports collected by a newly designed Citizen Science APP. A maximum density of 329 signals per 0.01 km2 was recorded at south-west of the odour sources investigated.

Coarctation of the aorta (CoA) comprises 5–7% of congenital heart disease and can present as an isolated narrowing in the aortic arch just distal to the left subclavian artery or can be associated with cardiac abnormalities such as a bicuspid aortic valve, aortopathy, or ventricular septal defects. With the advances in the medical field, intervention on CoA can either be via surgical repair or endovascular stenting. Echocardiography is the mainstay in diagnosing CoA, with tomographic imaging such as magnetic resonance imaging (MRI) or computed tomography providing supplementary assessment of the aorta, valves, and collateral vessels. We present a case of a young hypertensive male who was noted to have a continuous cardiac murmur with diagnostic Doppler pattern of CoA on echocardiography that normalized soon after percutaneous stenting.

BackgroundEvidence of the association between AMplitude Spectral Area (AMSA) of ventricular fibrillation and outcome after out-of-hospital cardiac arrest (OHCA) is limited to short-term follow-up. In this study, we assess whether AMSA can stratify the risk of death or poor neurological outcome at 30 days and 1 year after OHCA in patients with an initial shockable rhythm or with an initial non-shockable rhythm converted to a shockable one.MethodsThis is a multicentre retrospective study of prospectively collected data in two European Utstein-based OHCA registries. We included all cases of OHCAs with at least one manual defibrillation. AMSA values were calculated after data extraction from the monitors/defibrillators used in the field by using a 2-s pre-shock electrocardiogram interval. The first detected AMSA value, the maximum value, the average value, and the minimum value were computed, and their outcome prediction accuracy was compared. Multivariable Cox regression models were run for both 30-day and 1-year deaths or poor neurological outcomes. Neurological cerebral performance category 1–2 was considered a good neurological outcome.ResultsOut of the 578 patients included, 494 (85%) died and 10 (2%) had a poor neurological outcome at 30 days. All the AMSA values considered (first value, maximum, average, and minimum) were significantly higher in survivors with good neurological outcome at 30 days. The average AMSA showed the highest area under the receiver operating characteristic curve (0.778, 95% CI: 0.7–0.8, p

PURPOSE: Patients with BRAF V600 / NRAS Q61 wild-type melanoma who progress after immune checkpoint inhibitors (ICIs) have a poor prognosis. MEK inhibition has shown activity in this patient population but is associated with treatment-limiting skin toxicity. Combining a BRAF inhibitor with a MEK inhibitor is associated with less skin toxicity. METHODS: This phase II trial investigated trametinib (2 mg once daily) in patients with advanced BRAF V600 / NRAS Q61 wild-type, ICI-refractory melanoma. In case of treatment-limiting skin toxicity, low-dose dabrafenib (50 mg twice daily) was added to trametinib. After a trial amendment, both drugs were combined up-front. The confirmed objective response rate (cORR) served as the primary end point. RESULTS: Twenty-four patients were included (50% male; median age 57 years; 92% Eastern Cooperative Oncology Group Performance Status 0-2; 75% stage IV-M1c/stage IV-M1d; median number of prior therapies: two [range, 1-5]). Three patients were enrolled before and 21 patients after the amendment, respectively. Seven confirmed and one unconfirmed partial responses (PRs) were observed (cORR, 29.2%). The median duration of response was 16.6 weeks (95% CI, 5.5 to 27.7). Stable disease (SD) was the best response in an additional five patients. Among the responding patients, genetic alterations causing mitogen-activated protein kinase (MAPK) pathway activation were documented in six patients. The disease control rate in patients with MAPK pathway–activating alterations was 64.3% (five confirmed PR, one unconfirmed PR, and three SD). The median progression-free survival was 13.3 weeks (95% CI, 3.5 to 23.1), and the median overall survival was 54.3 weeks (95% CI, 37.9 to 70.6). Adding low-dose dabrafenib to trametinib effectively mitigated or prevented treatment-limiting trametinib-related skin toxicity. CONCLUSION: The combination of trametinib plus low-dose dabrafenib demonstrated encouraging efficacy and effective mitigation of skin toxicity in patients with advanced, ICI-pretreated BRAF V600 / NRAS Q61 wild-type melanoma patients. MAPK pathway–activating alterations hold promise as a predictive biomarker. [ABSTRACT FROM AUTHOR]

Background: A reversal of time difference between the onset of early diastolic velocity (e') during tissue Doppler imaging and the onset of mitral inflow (E) has been observed in cases of elevated left atrial pressure. Whether this interval (Te'-E) may be useful to assess right atrial pressure has never been investigated, neither in healthy subjects nor in pulmonary hypertension patients. Methods: Right ventricular Te'-E was assessed in patients with pre-capillary pulmonary hypertension and compared with healthy volunteers who underwent comprehensive echocardiography examination. Te'-E is the difference between the interval from R wave at the superimposed electrocardiogram to the e' wave during right ventricular tissue Doppler imaging and the interval from the R wave to transtricuspid E wave during pulsed wave Doppler imaging. Right atrial pressure was invasively measured in pulmonary hypertension patients. Results: Fifty-six patients were enrolled. Te'-E was prolonged in pulmonary hypertension subjects compared with healthy subjects (p < 0.001). Amongst the pulmonary hypertension patients, strong correlations were found between Te'-E and right atrial pressure (r = −0.885, p < 0.001), systolic pulmonary pressure (r = −0.85, p < 0.001) and the duration of tricuspid regurgitation (r = 0.72, p < 0.001). The area under the receiver operating characteristic curve of Te'-E in identifying right atrial pressure higher than 15 mm of mercury was 0.992 (sensitivity 100%, specificity 83%). Conclusions: In contrast to the left ventricle, there is a delay in the proto-diastolic filling in pulmonary hypertension patients, which correlates with the increase in systolic pulmonary arterial pressure, right atrial pressure, tricuspid regurgitation duration and restrictive diastolic pattern. [ABSTRACT FROM AUTHOR]

Background: Angiosarcomas are rare tumors that can be difficult to diagnose due to subtle changes in the vascular endothelium. When there is evidence to suggest malignancy, such as a pathologic fracture, further investigation is needed, and a high suspicion for angiosarcoma needs to be present so that appropriate immunohistochemical stains are utilized on biopsied tissue. In situations where such suspicion is high and prior biopsies have been negative, performance of splenectomy, can be both diagnostic and therapeutic when splenomegaly is present. Case Report: This is a case of a 52-year-old woman with splenomegaly, initially attributed to infection, in the setting of upper respiratory symptoms and thrombocytopenia. Three months later, however, she presented with back pain. Imaging showed lytic bone lesions with pathologic vertebral fracture and numerous liver lesions that were too small to characterize further. Initial biopsies of the liver and bone did not reveal a pathologic process. Several months later, still without a unifying diagnosis, she presented to our institution. MRI of the brain was done for neurologic concerns and showed pathologic enhancement in the calvarium. A PET scan showed diffuse avidity of the skeleton and spleen. After discussing the case with a hematologist, splenectomy was performed for both diagnostic and therapeutic purposes. Angiosarcoma was identified in the spleen and in a PET-directed bone biopsy. With a definitive diagnosis, she returned home and subsequently elected to pursue hospice care. Conclusion: When there is a high clinical suspicion for malignant angiosarcoma, a multidisciplinary approach is necessary to direct both tissue acquisition and necessary histochemical staining. [ABSTRACT FROM AUTHOR]

Primary palliative care is a core component of nursing practice for which all students must receive formal education. Through competency-based education, nursing students develop the knowledge, attitudes, and skills to deliver quality primary palliative care before they transition to practice. Nurse educators in academic and practice settings should use reliable and valid means to evaluate student learning across cognitive, affective, and psychomotor domains. Expert faculty conducted a literature review to identify published instruments that evaluate primary palliative care student learning outcomes. Selected articles were required to include instrument reliability, validity, or both. The literature search yielded 20 articles that report on the development and testing of 21 instruments. Findings are organized into 3 learning domains that encompass 5 outcomes. Four instruments assess knowledge within the cognitive domain. In the affective domain, 3 instruments assess attitudes about caring for seriously ill or dying patients, 7 assess attitudes about death, and 5 assess self-efficacy. Competence and competency are evaluated in the psychomotor domain with 4 tools. Instrument implementation considerations within each domain are discussed. Faculty are encouraged to use robust evaluation measures such as those identified in the literature review to measure primary palliative care learning outcomes within a competency-based education framework. [ABSTRACT FROM AUTHOR]

Substance use disorder (SUD) affects more than 1 in 6 Americans older than 12 years and has become an increasingly relevant topic in palliative care. Lack of clear guidelines and fragmented care results in patient safety concerns and poor outcomes. This rapid review aims to present the current literature on opioid contracts/ agreements, prescription drug monitoring database access, opioid risk assessment tools, and urine drug screening in the palliative care setting. Through a systematic process, we identified 19 articles published between 2018 and 2023 that pertained to substance use disorder and palliative care. Current risk mitigation strategies include prescription drug monitoring, opioid use agreements, risk assessment tools, urine drug screening, and the use of buprenorphine to manage pain. Prescription drug monitoring programs are state-based electronic databases that track controlled substances, and there are numerous risk assessment tools. Urine drug screening involves the use of both immunoassay and confirmatory chromatography to determine the presence or absence of either the prescribed controlled substance or unexpected findings including illicit drugs or prescription-controlled substances that are not prescribed to the patient. The goal of mitigating risk and reducing harm while providing expert symptom management is the challenge that palliative care transdisciplinary teams face as they continue to care for patients with substance use disorder. This review points to the need for further research on how to incorporate these harm-reducing strategies into clinical practice. [ABSTRACT FROM AUTHOR]

Background and purpose: Preclinical studies of amyotrophic lateral sclerosis (ALS) have shown altered endocannabinoid (eCB) signalling that may contribute to the disease. Results from human studies are sparse and inconclusive. The aim of this study was to determine the association between serum levels of eCBs or their congeners, the so‐called endocannabinoidome, and disease status and activity in ALS patients. Methods: Serum concentrations of 2‐arachidonoylglycerol and N‐arachidonoylethanolamine (AEA), and AEA congeners palmitoylethanolamide (PEA), oleoylethanolamide (OEA), eicosapentaenoylethanolamide (EPEA), 2‐docosahexaenoylglycerol (2‐DHG) and docosahexaenoylethanolamide (DHEA) were measured in samples from 65 ALS patients, 32 healthy controls (HCs) and 16 neurological disease controls (NALS). A subset of 46 ALS patients underwent a longitudinal study. Disease activity and progression were correlated with eCB and congener levels. Results: Most circulating mediators were higher in ALS than HCs (all p < 0.001), but not NALS. Across clinical stages, ALS patients showed increased levels of PEA, OEA and EPEA (all p < 0.02), which were confirmed by the longitudinal study (all p < 0.03). Serum PEA and OEA levels were independent predictors of survival and OEA levels were higher in patients complaining of appetite loss. Cluster analysis revealed two distinct profiles of circulating mediators associated with corresponding patterns of disease activity (severe vs. mild). Patients belonging to the 'severe' cluster showed significantly higher levels of OEA and PEA and lower levels of 2‐DHG compared to NALS and HCs. Conclusion: Circulating endocannabinoidome profiles are indicative of disease activity, thus possibly paving the way to a personalized, rather than a 'one‐fits‐all', therapeutic approach targeting the endocannabinoidome. [ABSTRACT FROM AUTHOR]

Rural communities in the United States are frequently marginalized and misrepresented. These communities face unique challenges, such as limited access to health care, nutritious food, and clean water, that contribute to persistent health disparities. This article presents the CARE (Complex, Access, Resourceful, Extraordinary) framework, which illustrates the dichotomy of rurality—its negative and positive aspects—in order to inform the development of palliative care delivery in rural settings. Various palliative care models are described that address access gaps, bolster provider capacity, and increase the provision of specialty palliative care. However, workforce shortages and reimbursement structures restrict the expansion of these services. Nurses, the largest segment of the health care workforce and the most trusted professionals, must partner with interdisciplinary colleagues and rural communities to advocate for equitable and inclusive care. The authors present the CARE (Complex, Access, Resourceful, Extraordinary) framework, which illustrates the dichotomy of rurality—its negative and positive aspects—in order to inform the development of palliative care delivery in rural settings. [ABSTRACT FROM AUTHOR]

Dyspnea is the most common and activity-limiting symptom for those with chronic obstructive pulmonary disease (COPD). Treatment is complex, palliative care (PC) dyspnea relief interventions are poorly understood, and PC remains underutilized in COPD despite national guidelines and recommendations. The purpose of this rapid review was to explore the concept of dyspnea and role of PC through the lens of providers, caregivers, and patients with COPD. A systematic approach for synthesis was used to identify 13 articles published between January 2018 and October 2023. Team members compared data via visualization and theme clustering to identify key conclusions describing operationalization of dyspnea, management, and PC implications. Dyspnea operationalization was challenging, with inconsistent measurement and terminology. Dyspnea was a significant burden in COPD and contributed to complexity of treatment. Opioids were used most often to treat dyspnea, but provider perspectives and biases can influence treatment decisions and perceptions of opioid therapy by the patient and caregiver. Evidence-based clinical practice guidelines and policies are needed to clarify the use of opioid therapy for dyspnea management to reduce stigmatization and barriers to treatment. Provider education should emphasize a multipronged approach to treatment of dyspnea in COPD with integration of PC early in the care continuum. [ABSTRACT FROM AUTHOR]

Community-based palliative care (CBPC) models address the growing needs of patients and caregivers with chronic and serious illnesses. From pediatrics to geriatrics, individuals prefer to receive care within their local community and at home. Delivering care at the community level and within the home improves health outcomes, reduces disparities, and supports local economic activity. Various models of CBPC have developed through partnerships with existing services, such as home health agencies, but ongoing challenges and barriers exist for further expansion of specialty palliative care. Advanced practice registered nurses increasingly manage chronic and serious illnesses and are essential for all health care teams, particularly for CBPC. As trusted providers within the community, advanced practice registered nurses create lasting relationships that allow for meaningful exchanges with patients and caregivers. This article reviewed the concept and features of CBPC offered within the United States and describes an advanced practice registered nurse-led embedded palliative care program for advanced lung disease. [ABSTRACT FROM AUTHOR]

Genetic predisposition and dietary factors can impact cardiovascular disease (CVD) risk. Two important markers in assessing CVD risk are apolipoprotein (apo) B and apolipoprotein A1 plasma levels. These markers are measured as a ratio, with a high apoB:apoA1 ratio associated with increased CVD risk. Dietary and lifestyle recommendations are the cornerstone of managing primary and secondary CVD risk-mitigation strategies. One way to assess the impact of various dietary and lifestyle interventions on CVD risk is to evaluate the changes in CVD risk markers, such as apoB, apoA1, and apoB:apoA1 ratio. Various human studies have demonstrated the impact of dietary, macronutrient, and micronutrient interventions on apoB and apoA1 status. This review aims to elucidate dietary, macronutrient, micronutrient, and nutrigenetic considerations for impacting apoB and apoA1 levels. A low-carbohydrate, high-saturated-fat diet, low fiber intake, low vitamin and mineral intake, and zinc and iron deficiency are associated with an elevated apoB:apoA1 ratio. The Mediterranean diet, vegan diet, fermented dairy products, lower sugar intake, higher protein intake, higher polyunsaturated fat intake, and an omega-3–rich diet are associated with a decreased apoB:apoA1 ratio. Micronutrients associated with a decreased apoB:apoA1 ratio include vitamin D sufficiency, increased serum vitamin C, and magnesium. Variants in the APOE, APOA1, and FADS2 genes may alter the apoB:apoA1 ratio in response to various dietary interventions. When accounting for factors that may favorably alter the apoB:apoA1 ratio, researchers should consider a healthy diet sufficient in polyunsaturated fats, vitamins, minerals, trace minerals, and lower excess sugars. [ABSTRACT FROM AUTHOR]

Graphical user interface (GUI) testing plays a pivotal role in ensuring the quality and functionality of mobile apps. In this context, exploratory testing (ET), a distinctive methodology in which individual testers pursue a creative, and experience‐based approach to test design, is often used as an alternative or in addition to traditional scripted testing. Managing the exploratory testing process is a challenging task that can easily result either in wasteful spending or in inadequate software quality, due to the relative unpredictability of exploratory testing activities, which depend on the skills and abilities of individual testers. A number of works have investigated the diversity of testers' performance when using ET strategies, often in a crowdtesting setting. These works, however, investigated ET effectiveness in detecting bugs, and not in scenarios in which the goal is to generate a re‐executable test suite, as well. Moreover, less work has been conducted on evaluating the impact of adopting different exploratory testing strategies. As a first step toward filling this gap in the literature, in this work, we conduct an empirical evaluation involving four open‐source Android apps and 20 masters students that we believe can be representative of practitioners partaking in exploratory testing activities. The students were asked to generate test suites for the apps using a capture and replay tool and different exploratory testing strategies. We then compare the effectiveness, in terms of aggregate code coverage that different‐sized groups of students using different exploratory testing strategies may achieve. Results provide deeper insights into code coverage dynamics to project managers interested in using exploratory approaches to test simple Android apps, on which they can make more informed decisions. [ABSTRACT FROM AUTHOR]