Body mass index-dependent immunological profile changes after left ventricular assist device implantation.

Purpose: Infection is a common complication following left ventricular assist device (LVAD) implantation. Patients with obesity are particularly at risk due to their high percentage of adipose tissue and the resulting chronic inflammatory state and resulting immunological changes. This study investigated changes of immunological parameters in relation to body mass index (BMI) during the first year after LVAD implantation. Methods: Blood samples were obtained prior to LVAD implantation and at 3 (1st FU), 6 (2nd FU) and 12 mo (3rd FU) after LVAD implantation. Patients were divided into three groups (normal weight: BMI of 18.5-24.9 kg/m2; n=12; pre-obesity: 25.0-29.9 kg/m2; n=15; obesity: ≥ 30.0 kg/m2; n=17) based on their BMI at the time of LVAD implantation. Flow cytometric analyses for CD4+ and CD8+ T cells, regulatory T cells (Tregs), B cells as well as dendritic cells (DCs) were performed. Results: After LVAD implantation, obese patients (0.51 ± 0.20%) showed a higher proportion of overall DCs than normal-weight (0.28 ± 0.10%) and pre-obese patients (0.32 ± 0.11%, p<0.01) at 3rd FU. The proportion of BDCA3+ myeloid DCs was lower in obese patients (64.3 ± 26.5%) compared to normal-weight patients (82.7 ± 10.0%, pnormal-weight vs. obesity=0.05) at 2nd FU after LVAD implantation. The analysis of BDCA4+ plasmacytoid DCs revealed a reduced proportion in pre-obese (21.1 ± 9.8%, pnormal-weight vs. pre-obesity=0.01) and obese patients (23.7 ± 10.6%, pnormal-weight vs. obesity=0.05) compared to normal-weight patients (33.1 ± 8.2%) in the 1st FU. T cell analysis showed that CD4+ T cells of obese patients (62.4 ± 9.0%) significantly increased in comparison to pre-obese patients (52.7 ± 10.0%, ppre-obesity vs. obesity=0.05) and CD8+ T cells were lower in obese patients (31.8 ± 8.5%) than in normal-weight patients (42.4 ± 14.2%; pnormal-weight vs. obesity=0.04) at the 3rd FU. Furthermore, we observed significantly reduced proportions of Tregs in pre-obese patients compared to normal-weight and obese patients at 2nd FU (p=0.02) and 3rd FU (p=0.01) after LVAD implantation. Conclusion: This study reported changes of the innate and adaptive immune system of pre-obese and obese compared to normal-weight patients one year after LVAD implantation. DCs and their subsets, CD8+ T cells and Tregs were affected immune cell populations that indicate immunological changes which might increase the incidence of postoperative infection.

EEG background frequency is associated with discharge outcomes in non-ICU hospitalized patients with COVID-19.

Objective: To assess risk factors for encephalopathy in non-ICU hospitalized patients with COVID-19 and the effect of encephalopathy on short-term outcomes. Methods: We collected clinical and electrophysiological characteristics of fifty patients with COVID-19 infection admitted to a ward service and who had an electroencephalogram (EEG) performed. Associations with short-term outcomes including hospital length of stay and discharge disposition were determined from univariate and multivariate statistical analysis. Results: Clinical delirium was associated with encephalopathy on EEG, cefepime use was associated with increased length of stay, and of all factors analyzed, background frequency on EEG alone was correlated with discharge disposition. Conclusion: Encephalopathy is one of the major determinants of short-term outcomes in hospitalized non-ICU patients with COVID-19.

Analysis of the extent of limbic system changes in multiple sclerosis using FreeSurfer and voxel-based morphometry approaches.

BACKGROUND AND PURPOSE: The limbic brain is involved in diverse cognitive, emotional, and autonomic functions. Injury of the various parts of the limbic system have been correlated with clinical deficits in MS. The purpose of this study was to comprehensively examine different regions of the subcortical limbic system to assess the extent of damage within this entire system as it may be pertinent in correlating with specific aspects of cognitive and behavioral dysfunction in MS by using a fully automated, unbiased segmentation approach. METHODS: Sixty-seven subjects were included in this study, including 52 with multiple sclerosis (MS) and 15 healthy controls. Only patients with stable MS disease, without any relapses, MRI activity, or disability progression were included. Subcortical limbic system segmentation was performed using the FreeSurfer pipeline ScLimbic, which provides volumes for fornix, mammillary bodies, hypothalamus, septal nuclei, nucleus accumbens, and basal forebrain. Hippocampus and anterior thalamic nuclei were added as additional components of the limbic circuitry, also segmented through FreeSurfer. Whole limbic region mask was generated by combining these structures and used for Voxel-based morphometry (VBM) analysis. RESULTS: The mean [95% confidence interval] of the total limbic system volume was lower (0.22% [0.21-0.23]) in MS compared to healthy controls (0.27%, [0.25-0.29], p < .001). Pairwise comparisons of individual limbic regions between MS and controls was significant in the nucleus accumbens (0.046%, [0.043-0.050] vs. 0.059%, [0.051-0.066], p = .005), hypothalamus (0.062%, [0.059-0.065] vs. 0.074%, [0.068-0.081], p = .001), basal forebrain (0.038%, [0.036-0.040] vs. 0.047%, [0.042-0.051], p = .001), hippocampus (0.47%, [0.45-0.49] vs. 0.53%, [0.49-0.57], p = .004), and anterior thalamus (0.077%, [0.072-0.082] vs. 0.093%, [0.084-0.10], p = .001) after Bonferroni correction. Volume of several limbic regions was significantly correlated with T2 lesion burden and brain parenchymal fraction (BPF). Multiple regression model showed minimal influence of BPF on limbic brain volume and no influence of other demographic and disease state variables. VBM analysis showed cluster differences in the fornix and anterior thalamic nuclei at threshold p < 0.05 after adjusting for covariates but the results were insignificant after family-wise error corrections. CONCLUSIONS: The results show evidence that brain volume loss is fairly extensive in the limbic brain. Given the significance of the limbic system in many disease states including MS, such volumetric analyses can be expanded to studying cognitive and emotional disturbances in larger clinical trials. FreeSurfer ScLimbic pipeline provided an efficient and reliable methodology for examining many of the subcortical structures related to the limbic brain.

Effects of the WRITE Symptoms Interventions on Symptoms and Quality of Life Among Patients With Recurrent Ovarian Cancers: An NRG Oncology/GOG Study (GOG-0259).

PURPOSE: GOG-259 was a 3-arm randomized controlled trial of two web-based symptom management interventions for patients with recurrent ovarian cancer. Primary aims were to compare the efficacy of the nurse-guided (Nurse-WRITE) and self-directed (SD-WRITE) interventions to Enhanced Usual Care (EUC) in improving symptoms (burden and controllability) and quality of life (QOL). METHODS: Patients with recurrent or persistent ovarian, fallopian, or primary peritoneal cancer with 3+ symptoms were eligible for the study. Participants completed baseline (BL) surveys (symptom burden and controllability and QOL) before random assignment. WRITE interventions lasted 8 weeks to develop symptom management plans for three target symptoms. All women received EUC: monthly online symptom assessment with provider reports; online resources; and every 2-week e-mails. Outcomes were evaluated at 8 and 12 weeks after BL. Repeated-measures modeling with linear contrasts evaluated group by time effects on symptom burden, controllability, and QOL, controlling for key covariates. RESULTS: Participants (N = 497) reported mean age of 59.3 ± 9.2 years. At BL, 84% were receiving chemotherapy and reported a mean of 14.2 ± 4.9 concurrent symptoms, most commonly fatigue, constipation, and peripheral neuropathy. Symptom burden and QOL improved significantly over time (P < .001) for all three groups. A group by time interaction (P < .001) for symptom controllability was noted whereby both WRITE intervention groups had similar improvements from BL to 8 and 12 weeks, whereas EUC did not improve over time. CONCLUSION: Both WRITE Intervention groups showed significantly greater improvements in symptom controllability from BL to 8 and BL to 12 weeks compared with EUC. There were no significant differences between Nurse-WRITE and SD-WRITE. SD-WRITE has potential as a scalable intervention for a future implementation study.

A scoping review of unmet needs of caregivers of patients with pulmonary fibrosis.

PURPOSE OF REVIEW: Pulmonary fibrosis is an incurable lung disease that leads to significant morbidity. In many patients, pulmonary fibrosis is progressive causing debilitating dyspnea that impairs patients' ability to perform everyday tasks and maintain independence. Informal caregivers provide invaluable support for patients with pulmonary fibrosis; however, support for the caregiver is inadequate. The purpose of this scoping review is to identify unmet needs for caregivers of pulmonary fibrosis patients. RECENT FINDINGS: During the past 18 months, there has been an increase in studies about the impact of pulmonary fibrosis on the caregiver or carer of the patient with pulmonary fibrosis. These carers experience caregiver burden which includes negative psychological and physical effects on caregiver health because of the challenge in caring for someone with pulmonary fibrosis. Caregivers describe the need for help navigating the healthcare system. This includes supportive and informational needs, lack of access to comprehensive patient-centred care, geographically accessible specialty centres and psychological support for both patient and caregiver. SUMMARY: Caregivers of pulmonary fibrosis patients have numerous unmet care needs that include education about the disease, symptom management, financial assistance, access to specialty centres, advanced care planning and psychological support. This resulting caregiver burden can be alleviated with comprehensive support tailored throughout the disease course.

Immune Monitoring Assay for Extracorporeal Photopheresis Treatment Optimization After Heart Transplantation.

Background: Extracorporeal photopheresis (ECP) induces immunological changes that lead to a reduced risk of transplant rejection. The aim of the present study was to determine optimum conditions for ECP treatment by analyzing a variety of tolerance-inducing immune cells to optimize the treatment. Methods: Ten ECP treatments were applied to each of 17 heart-transplant patients from month 3 to month 9 post-HTx. Blood samples were taken at baseline, three times during treatment, and four months after the last ECP treatment. The abundance of subsets of tolerance-inducing regulatory T cells (Tregs) and dendritic cells (DCs) in the samples was determined by flow cytometry. A multivariate statistical model describing the immunological status of rejection-free heart transplanted patients was used to visualize the patient-specific immunological improvement induced by ECP. Results: All BDCA+ DC subsets (BDCA1+ DCs: p < 0.01, BDCA2+ DCs: p < 0.01, BDCA3+ DCs: p < 0.01, BDCA4+ DCs: p < 0.01) as well as total Tregs(p < 0.01) and CD39+ Tregs(p < 0.01) increased during ECP treatment, while CD62L+ Tregs decreased (p < 0.01). The cell surface expression level of BDCA1 (p < 0.01) and BDCA4 (p < 0.01) on DCs as well as of CD120b (p < 0.01) on Tregs increased during the study period, while CD62L expression on Tregs decreased significantly (p = 0.04). The cell surface expression level of BDCA2 (p = 0.47) and BDCA3 (p = 0.22) on DCs as well as of CD39 (p = 0.14) and CD147 (p = 0.08) on Tregs remained constant during the study period. A cluster analysis showed that ECP treatment led to a sustained immunological improvement. Conclusions: We developed an immune monitoring assay for ECP treatment after heart transplantation by analyzing changes in tolerance-inducing immune cells. This assay allowed differentiation of patients who did and did not show immunological improvement. Based on these results, we propose classification criteria that may allow optimization of the duration of ECP treatment.

Nurse-Led Palliative Care Clinical Trial Improves Knowledge and Preparedness in Caregivers of Patients with Idiopathic Pulmonary Fibrosis.

Rationale: Patients with idiopathic pulmonary fibrosis (IPF) and their caregivers experience stress, symptom burden, poor quality of life, and inadequate preparedness for end-of-life (EOL) care planning as the disease progresses. The hypothesis for this study was that the early introduction of palliative care in the course of IPF would improve knowledge and preparation for EOL, patient-reported outcomes, and advance care planning in patients with IPF and their caregivers. Objectives: We sought to determine the feasibility, acceptability, and efficacy of a nurse-led early palliative care intervention entitled "A Program of SUPPORT" (Symptom management, Understanding the disease, Pulmonary rehabilitation, Palliative care, Oxygen therapy, Research participation, and Transplantation) in patients with IPF and their caregivers. Methods: Patients with IPF (diagnosed in the year previous to their initial center visit) from the University of Pittsburgh Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease at University of Pittsburgh Medical Center-together with their caregivers-were randomized to receive the intervention "A Program of SUPPORT" or usual care. This included a total of three research visits aligned with their clinic visit over a period of 6 to 8 months. We measured feasibility, acceptability, and efficacy of this intervention. Results: A total of 136 patient/caregiver dyads were eligible, and a total of 76 dyads were enrolled and participated. Participants were predominately White males >65 years old. Thirteen percent did not have an identified caregiver. Feasibility was limited; 56% of eligible dyads were enrolled. Eligible dyads (24%) were interested in participating but too fatigued to stay after their clinic visit. There was high attrition (20% of participants died before the study was completed). "A Program of SUPPORT" was acceptable to participants. Efficacy demonstrated a significant improvement in caregiver's knowledge, disease preparedness, and confidence in caring for the patient as well as an improvement in knowledge and advance care planning completion in patient participants. Conclusions: Patients with IPF and their caregivers have unmet needs regarding knowledge of their disease, self-management strategies, and preparedness for EOL planning. This nurse-led intervention demonstrated acceptability and efficacy in knowledge and advance care planning completion in patients and in knowledge, disease preparedness, and confidence in caregivers. Future research should identify additional strategies, including telemedicine resources to reach additional patients and their caregivers earlier in their disease course. Clinical trial registered with clinicaltrials.gov (NCT02929017).

Rapid development of seizures and PRES in a COVID-19 patient.

Neurological dysfunction has been noted in up to 36% of patients hospitalized with COVID-19, and a variety of mechanisms of neurological injury are possible. Here we report the rapid development of PRES and acute seizures in a patient with COVID-19 infection and sickle cell disease. The combination of COVID and sickle cell disease may raise the risk of PRES and could contribute to the higher mortality rate of COVID in patients with sickle cell disease.

Clinical Characteristics of Multiple Sclerosis in African-Americans.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that affects nearly 1 million people in the USA and has the potential to profoundly affect physical ability and income potential at a young age. Since a landmark paper was published in 2014, few studies have looked at differences in MS disease characteristics between African-American and Caucasian patients. RECENT FINDINGS: African-American patients often have a more severe MS disease course, as well as biomarker data which can portend a worse prognosis. While the sample sizes are usually quite small, subgroup analyses of African-American patients have been performed to evaluate efficacy of disease-modifying treatments as compared with the entire study population, made up of primarily Caucasians. In an era where we strive for personalized medicine, understanding racial differences in MS may help us better treat African-American patients in the future.

Clinical Features of Pediatric Complex Regional Pain Syndrome: A 5-Year Retrospective Chart Review.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a painful condition of a limb characterized by a constellation of symptoms. Little is known about the clinical features of pediatric CRPS, with fewer than a dozen studies published to date. The aim of this study was to explore the clinical course of pediatric CRPS, with emphasis on clinical features and disease outcomes. A secondary aim was to discern differences in clinical features of pediatric CRPS with and without related movement disorders, and between children who had a favorable and unfavorable outcome. MATERIALS AND METHODS: We carried out a retrospective chart review of children with CRPS who presented to a pediatric Chronic Pain Clinic in Canada over a 5-year period (2012 to 2016). RESULTS: The study identified 59 children with CRPS (mean age: 12.7±2.5; 74.6% female; 72.9% lower extremity). In total, 87% (n=48) of children experienced complete resolution or significant improvement of CRPS, with a relapse rate of 15%. Overall, 25% (n=15) had a CRPS-related movement disorder. There were no differences in the clinical features of pediatric CRPS with or without related movement disorders. Children who experienced a favorable outcome had a significantly shorter symptom duration at the initial visit in comparison with children who experienced an unfavorable outcome. DISCUSSION: In this cohort, pediatric CRPS was most common in girls around the age of 12, usually in the lower extremity, and most experienced a favorable outcome. Further research is needed to better understand the prognosis and relapse rate of pediatric CRPS.

Oncology Nurse Practitioner Web Education Resource(ONc-PoWER): An Evaluation of a Web-Enhanced Education Resource for Nurse Practitioners Who Are New to Cancer Care.

The nurse practitioner (NP) new to an advanced role in a specialty practice may find the orientation period challenging while expanding his or her professional knowledge base. The Oncology Nurse Practitioner Web Education Resource (ONc-PoWER), a web-enhanced continuing education program, provides training for both the oncology NP (ONP) new to cancer care (i.e., within the first year) and his or her on-site mentor. The Oncology Nurse Practitioner Web Education Resource promotes essential didactic and skills development via five modules. A total of 103 dyads (i.e., a new ONP and his or her mentor) were recruited from 27 states to participate in ONc-PoWER, and 79 dyads completed surveys to evaluate the program. Data were collected between April 2012 and October 2016. We observed statistical significance (p = .000) between pre- and post-program self-assessment of cancer care knowledge and confidence in delivering cancer care among ONPs. Moreover, mentors rated the program favorably. Mentor agreement concerning whether or not the ONPs were able to successfully perform 30 core clinical skills ranged from a low of 93% to a high of 100%. Furthermore, mean scores of the course satisfaction survey demonstrate that each ONc-PoWER objective either met or exceeded learner expectations.

Randomised clinical trial of an early palliative care intervention (SUPPORT) for patients with idiopathic pulmonary fibrosis (IPF) and their caregivers: protocol and key design considerations.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF), a progressive life-limiting lung disease affects approximately 128 000 newly diagnosed individuals in the USA annually. IPF, a disease of ageing associated with intense medical and financial burden, is expected to grow in incidence globally. Median survival from diagnosis is 3.8 years, and many of these patients succumb to a rapid death within 6 months. Despite the fatal prognosis, we have found that patients and caregivers often fail to understand the poor prognosis as the disease relentlessly progresses. Based on feedback from patients and families living with IPF, we developed the S-Symptom Management, U-Understanding the Disease, P-Pulmonary Rehabilitation, P-Palliative Care, O-Oxygen Therapy, R-Research Considerations and T-Transplantation ('SUPPORT') intervention to increase knowledge of the disease, teach self-management strategies and facilitate preparedness with end of life (EOL) planning. METHODS: This study is a randomised trial to test the efficacy of SUPPORT intervention compared with routine care in patients with IPF and their caregivers delivered after three clinical visits. We are recruiting a cohort of 64 new IPF patient/caregiver dyads (32 for each dyad). RESULTS: The trial will evaluate whether the SUPPORT intervention decreases stress, improves symptom burden, quality of life, preparedness and advance care planning for patients and caregivers, quality of dying and death for caregivers if the patient dies during the course of the study, as well as assess the impact of primary palliative care on healthcare resource use near the EOL. CONCLUSION: By increasing knowledge of the disease, teaching self-management strategies and facilitating preparedness with EOL planning, we will address a critical gap in the care of patients with IPF. TRIAL REGISTRATION NUMBER: NCT02929017; Pre-results.

Creating Quality Online Materials for Specialty Nurse Practitioner Content: Filling a Need for the Graduate Nurse Practitioner.

Nurse practitioners are entering specialized areas of practice immediately after graduation from nurse practitioner (NP) education and certification and are finding employment in specialized areas such as oncology. Rapidly achieving a knowledge base in this highly specialized area of medicine coupled with the stress of the new nurse practitioner role can lead to a very difficult orientation and transition period. There are several methods to provide specialized education to NPs during their orientation period. Unfortunately, limitations such as a lack of motivated mentors, limited opportunities to practice the desired skill set or a lack of structure in regards to curriculum quality, and the learning needs of the new nurse hinder the NP's transition to practice. In response to either inadequate or non-standardized orientation to the specialty role of the oncology NP (ONP), a web-enhanced educational tool, funded through the National Cancer Institute, was developed for use in the USA: Oncology Nurse Practitioner Web Education Resource (ONc-PoWER). The development of ONc-PoWER was based upon essential education for NPs new to cancer care, adult learning theory, Bloom's Taxonomy, and foundations of quality online education. The five interactive web-based modules provide specialized education for the nurse practitioner new to oncology along with an on-site mentor to assist the NP in applying the course content to clinical practice.

Assay validation of phosphorylated S6 ribosomal protein for a pharmacodynamic monitoring of mTOR-inhibitors in peripheral human blood.

BACKGROUND: Therapeutic drug monitoring (TDM) of immunosuppressive drugs after organ transplantation is based on measuring blood levels alone, which often results in under- or over-immunosuppression. Previous studies have shown the potential of measuring pharmacodynamic drug effects for TDM, but assessment of biomarkers for individual drugs is still not clinical routine. Therefore, we validated a specific assay to measure the pharmacodynamic effects of mammalian target of rapamycin (mTOR)-inhibitors on phosphorylated S6 ribosomal protein (p-S6RP), a downstream target of mTOR. METHODS: Clinical relevant concentrations of sirolimus (SRL, 0.9-91.4 µg/L), cyclosporine A (CsA, 75.1-1202 µg/L), mycophenolate acid (MPA, 0.08-3.2 mg/L), or dexamethasone (DEX, 0.5-200 ng/mL) were added to whole-blood from healthy volunteers. Activated whole-blood was analyzed by phospho-flow cytometry to measure p-S6RP in T cells. RESULTS: Phospho-flow analysis revealed that SRL suppressed p-S6RP in human T cells in a dose-dependent manner with a half-maximal inhibitory concentration (IC(50)) at 19.8 nM and a maximal inhibitory effect (I(max) %) at 91.9%. Neither CsA, MPA, nor DEX inhibited mTOR-related S6RP-phosphorylation. Coefficient of variations from 0.03 to 0.05, 0.12 to 0.25, and 0.14 to 0.38 for intra-, interassay, and interindividual variability respectively, showed robustness of our assay. Furthermore, samples can be stored at RT or 4°C up to 2 h after withdrawal. CONCLUSION: We validated a robust whole-blood assay that allows the specific measurement of SRL- and everolimus-induced inhibition of T cells' function through detection of p-S6RP. Future studies in organ transplanted recipients will show if this assay has the potential to enhance a TDM for mTOR-inhibitor drugs in combination therapies.

Short-term effects of a moderate fish oil or soybean oil supplementation on postprandial glucose and insulin responses in healthy horses.

The aim of this study was to investigate the effects of fat supplementation on postprandial glycaemic and insulinaemic responses in horses fed a corn meal. Four horses were fed three different diets: (1) cracked corn (CC), (2) cracked corn with soybean oil (CC+SBO), and (3) cracked corn with fish oil (CC+FO). Each diet was adjusted so there was a starch intake of 2 g/kg bodyweight (BW) and an intake of 0.2 mL/kg BW of FO and SBO. The increases in mean plasma glucose and insulin concentrations, peak values, and areas under the curve were similar for all diets (time P<0.05, diet not significant). The addition of FO or SBO at 0.2 mL/kg BW to a starchy meal did not affect acute glucose and insulin responses. To avoid high postprandial glycaemic and insulinaemic responses feeding strategies should be designed primarily to reduce starch intake rather than the addition of fat.