Advanced Practice Nursing and CAR-T Cell Therapy: Opportunities, Challenges and Future Directions.

OBJECTIVES: Chimeric antigen receptor (CAR)-T cell therapy is a new treatment for patients with myeloma and other B cell malignancies where advanced practice nurses (APN) can make a great contribution. The aim of this review is to identify key aspects of current literature relevant to APNs working with this population. METHODS: Discussion of selected peer-reviewed literature and best practice guidelines found through electronic database searches (CINAHL, MEDLINE). RESULTS: Although few APN roles in CAR-T cell therapy have been published to date, recent research suggests that the APN is central to the care of these patients. They are essential for continuity of care and navigation through the treatment process, providing an important and consistent point of contact for patients' and carers' anxieties and uncertainties. APNs play a central role in symptom management, as they constantly incorporate new experience and scientific findings into the refinement of existing protocols. The continuum of care extends far beyond the inpatient stay and addresses symptoms that may persist long after cytokine release syndrome and neurotoxicity have resolved. The APN may therefore make a relevant contribution to patients' health-related quality of life, given its likely correlation with the dynamics and intensity of treatment-related symptoms. The APN also takes on a leadership role in the treatment team. CONCLUSIONS: APNs use all core competencies to sustainably support and empower patients and caregivers. This is achieved through counseling and education, in addition to identifying, developing, and implementing evidence-based symptom management. They play pivotal roles in introducing new CAR-T cell products, educating teams, and advancing their role through APN networks. Finally, APNs are integral members of multiprofessional teams, supporting colleagues in ethically challenging patient situations. IMPLICATIONS FOR NURSING PRACTICE: APNs in the field of CAR-T cell therapy make an important contribution to the continuous care of patients, caregivers, and treatment teams.

Diverging role of epicardial adipose tissue across the entire heart failure spectrum.

AIMS: Epicardial adipose tissue (EAT) is a metabolically highly active tissue modulating numerous pathophysiological processes. The aim of this study was to investigate the association between EAT thickness and endothelial function in patients with heart failure (HF) across the entire ejection fraction spectrum. METHODS AND RESULTS: A total of 258 patients with HF with an ejection fraction across the entire spectrum [HF with reduced ejection fraction (HFrEF), n = 168, age 60.6 ± 11.2 years; HF with preserved ejection fraction (HFpEF), n = 50, mean age 65.1 ± 11.9 years; HF with mildly reduced ejection fraction (HFmrEF), n = 32, mean age 65 ± 12] were included. EAT was measured with transthoracic echocardiography. Vascular function was assessed with flicker-light-induced vasodilation of retinal arterioles (FIDart%) and flow-mediated dilatation (FMD%) in conduit arteries. Patients with HFrEF have less EAT compared with patients with HFpEF (4.2 ± 2 vs. 5.3 ± 2 mm, respectively, P < 0.001). Interestingly, EAT was significantly associated with impaired microvascular function (FIDart%; r = -0.213, P = 0.012) and FMD% (r = -0.186, P = 0.022), even after multivariate correction for confounding factors (age, body mass index, hypertension, and diabetes; standardized regression coefficient (SRC) = -0.184, P = 0.049 for FIDart% and SRC = -0.178, P = 0.043 for FMD%) in HFrEF but not in HFpEF. CONCLUSIONS: Although less EAT is present in HFrEF than in HFpEF, only in HFrEF EAT is associated with vascular dysfunction. The diverging role of EAT in HF and its switch to a functionally deleterious tissue promoting HF progression provide the rationale to specifically target EAT, in particular in patients with reduced ejection fraction.

Patient-reported experiences of cancer care related to the COVID-19 pandemic in Switzerland.

PURPOSE: This study aims to describe the experience of Swiss oncological patients during the COVID-19 pandemic. METHODS: A national multi-center study including five hospitals covering the three main language regions of Switzerland was conducted between March and July 2021. Patients with melanoma, breast, lung, or colon cancer receiving active systemic anti-cancer treatment at the time of the COVID-19 pandemic were included. We conducted semi-structured telephone or onsite interviews alongside the administration of distress and resilience-validated questionnaires. Thematic analysis was performed for the qualitative data and descriptive statistics for the quantitative data. RESULTS: Sixty-two cancer patients with a mean age of 61 (SD=14) (58% female) were interviewed. Based on the interviews, we identified that the experience of having cancer during the COVID-19 pandemic was related to five dimensions: psychological, social, support, healthcare, and vaccination. Three themes transverse the five dimensions: (a) needs, (b) positive changes, and (c) phases of the pandemic. In general, patients did not experience delays or disruptions in their cancer treatment nor felt additionally burdened by the pandemic. Lockdown and isolation were reported as mixed experiences (positive and negative), and access to vaccination reassured patients against the risk of infection and instilled hope to return to normalcy. Additionally, we found low distress levels (M=2.9; SD=2.5) and high resilience scores (M=7; SD=1.3) in these patients. CONCLUSION: Swiss patients with cancer did not express major needs or disruptions in their care during this period of the COVID-19 pandemic. Results identify the mixed experiences of patients and highlight the high resilience levels.

Systematic symptom screening in patients with advanced cancer treated in certified oncology centers: results of the prospective multicenter German KeSBa project.

PURPOSE: Guidelines recommend a structured symptom screening (SC) for especially advanced cancer patients (CPs). The aim of this multicenter German prospective quality assurance project KeSBa (Kennzahl Symptom- und Belastungserfassung) was to gain knowledge on SC procedures in Oncology Centers (OCs) for advanced cancer patients and a first impression on the consequences of SC. METHODS: The KeSBa project consisted of three phases: pilot, 3 months screening and feedback phase. Participating OCs decided to use either the Minimal Documentation System (MIDOS) or the Integrated Palliative care Outcome Scale (IPOS) and defined the cutoff values for positive screening results. RESULTS: Out of 172 certified German OCs, 40 (23%) participated in the KeSBa pilot phase, 29 (16.8%) in the 3 months screening phase using MIDOS (n = 18, 58.6%) or IPOS (n = 11, 41.3%) and in the feedback round. 25/29 performed paper-based screening (86.2%). 2.963 CPs were screened. Results were documented for 1255 (42.2%, SC +) positive and 874 (29.5%, SC-) negative screenings depending on the center´s schedules: 452 SC + CPs (28.4%) and 42 SC- CPs (2.6%) had contact to specialized palliative care or other supportive specialist teams afterwards, 458 SC + CPs (28.8%) and 605 SC- CPs (38.1%) remained in standard oncology care. In the feedback round missing resources (personal and IT) and improved communication were mentioned most often. CONCLUSION: Routine SC is feasible in advanced CPs treated in OCs but associated with considerable workload. In 42.2% of CPs SC was classified as positive, indicating the need of further diagnostics or professional judgment. SC requires staff and IT resources.

Symptom experience of multiple myeloma (syMMex) patients treated with autologous stem cell transplantation following high-dose melphalan: a descriptive longitudinal study.

PURPOSE: High-dose melphalan and autologous stem cell transplantation (ASCT) are associated with high symptom burden. This study aimed to explore multiple myeloma (MM) patients' experience of symptom frequency, intensity, and distress during therapy. METHODS: This descriptive longitudinal study enrolled 29 MM patients who completed the 43-item PROVIVO questionnaire, measuring symptom experience across the dimensions of frequency, intensity, and distress at four assessment points: hospital admission (T0), leucocyte nadir (T1), discharge (T2), and 30 days post discharge (T3). Symptom assessment covered five categories: (1) physical, (2) emotional, (3) cognitive, (4) male/female urogenital symptoms, and (5) follow-up care planning (e.g., financial problems). Results were displayed as heat maps and bubble graphs for each patient, differences between T0 and T4 individually assessed, and intensity (IMS) and mean distress scores (DMS) calculated on a scale from 0 to 4. RESULTS: The most frequent, intense, and distressing physical symptoms were fatigue, diarrhea, and decreased appetite. As expected, peak symptom intensity (decreased appetite 2.79) and distress (diarrhea 2.11) were reported during high-dose melphalan and the leucocyte nadir (T1). Thereafter, most symptoms' intensity and distress improved. Items on urogenital symptoms remained predominantly unanswered or patients were sexually inactive. CONCLUSIONS: PROVIVO enabled exploration of various dimensions of MM patients' symptom experiences, which differed substantially before and after ASCT. Our results suggest that high-dose melphalan, ASCT, and other intensive novel agent therapies warrant targeted symptom management programs that include focused patient support.

Vascular Effects of Eplerenone in Coronary Artery Disease With Preserved Ejection Fraction: A Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). Their role in patients without heart failure, particularly in patients with coronary artery disease (CAD) and preserved EF, is still a matter of debate. HYPOTHESIS: The MRA eplerenone on top of standard medical therapy improves endothelial dysfunction and other markers of vascular health in CAD patients with preserved EF. METHODS: In this double-blind, randomized, placebo-controlled study, 42 patients (mean age: 63.5 ± 9.1 years; 37 males) were randomized to 4-week treatment with eplerenone 25 mg daily or placebo. The primary endpoint was difference in endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery. Secondary endpoints included 24-hour blood pressure (BP), endothelial progenitor cells, and platelet adhesion. RESULTS: No difference in the primary endpoint FMD was noted after 4 weeks of treatment with eplerenone compared with placebo (FMD: 4.7% ± 2.0% and 4.9% ± 2.1%, respectively; P = 0.77). There were no significant differences between eplerenone and placebo in 24-hour BP (mean systolic BP: 126.9 ± 17.3 and 123.3 ± 9.7 mm Hg, P = 0.41; diastolic BP: 73.3 ± 12.9 and 72.0 ± 7.5 mm Hg, respectively, P = 0.69), number of endothelial progenitor cells, and platelet adhesion. CONCLUSIONS: Adding low-dose eplerenone to standard medical therapy did not improve important markers of vascular health in patients with CAD and preserved EF. Our results may help understand conflicting evidence from larger clinical trials on MRAs in patients with preserved EF.

Medical therapy of heart failure with reduced ejection fraction: current evidence and new developments.

Heart failure with reduced ejection fraction (HFrEF) is a common cardiovascular condition with a significant individual and societal burden. Although it was previously known as a palliative condition, medical drug therapies that were developed in the last four decades significantly reduced morbidity and mortality of the disease. The cornerstone of HFrEF therapy remains the blockade of the renin-angiotensin-aldosterone and the ß-adrenergic systems. This review aims to give an overview and update on established disease-modifying therapies in HFrEF, discuss advances and setbacks in the treatment of selected comorbidities and provide an outlook on upcoming therapies including the new concept of dual angiotensin receptor and neprilysin inhibition.

The good and the bad of neuroinflammation in multiple sclerosis.

Multiple sclerosis (MS) is the most common inflammatory, demyelinating, neurodegenerative disorder of the central nervous system (CNS). It is widely considered a T-cell mediated autoimmune disease that develops in genetically susceptible individuals, possibly under the influence of certain environmental trigger factors. The invasion of autoreactive CD4+ T-cells into the CNS is thought to be a central step that initiates the disease. Several other cell types, including CD8+ T-cells, B-cells and phagocytes appear to be involved in causing inflammation and eventually neurodegeneration. But inflammation is not entirely deleterious in MS. Evidence has accumulated in the recent years that show the importance of regulatory immune mechanisms which restrain tissue damage and initiate regeneration. More insight into the beneficial aspects of neuroinflammation might allow us to develop new treatment strategies for this enigmatic disease.

Gender differences in circulating levels of neutrophil extracellular traps in serum of multiple sclerosis patients.

Neutrophil extracellular traps (NETs) trap and kill pathogens very efficiently but also activate dendritic cells and prime T cells. Previously, we demonstrated that neutrophils are primed and circulating NETs are elevated in relapsing remitting multiple sclerosis (RRMS), a T cell-mediated autoimmune disease. Here, we demonstrate gender specific differences in circulating NETs but not in neutrophil priming in RRMS patients. Although the results from our systematic and in depth characterization of these patients argue against a major role of circulating NETs in this disease, they suggest that NETs may underlie gender-specific differences in MS pathogenesis.

Neutrophils in multiple sclerosis are characterized by a primed phenotype.

Neutrophils are armed with proteases with indiscriminate histotoxic potential, and to minimize tissue injury, their activation involves priming with inflammatory mediators before cells are fully activated in a second step. Here, we show that neutrophils in multiple sclerosis patients are more numerous and exhibit a primed state based on reduced apoptosis, higher expression of TLR-2, fMLP receptor, IL-8 receptor and CD43, enhanced degranulation and oxidative burst as well as higher levels of neutrophil extracellular traps in serum. The chronic inflammatory environment in multiple sclerosis probably underlies this inappropriate neutrophil priming, which may result in enhanced neutrophil activation during infection.