Improving Stroke Measure Compliance and Outcomes Through Hospital Collaboration.

Globally, national stroke registries have been shown to improve the quality of patient care and outcomes. However, registry utilization and implementation vary by country. In the United States, stroke-specific performance measures must be met to achieve and maintain stroke center certification awarded by the state or nationally accredited certifying bodies. The 2 stroke registries available in the United States are the American Heart Association Get With The Guidelines-Stroke registry, which is voluntary, and the Paul Coverdell National Acute Stroke Registry, funded competitively to states by the Centers for Disease Control and Prevention. Compliance with stroke processes of care is variable, and quality improvement initiatives among organizations have been shown to have an impact on improving stroke care delivery. However, the effectiveness of interorganizational continuous quality improvement approaches, especially among competing institutions, to improving stroke care is ambiguous, and no uniform governance for successful interhospital collaboration has been identified. The purpose of this article is to review national initiatives focused on interorganizational collaboration to improve stroke care delivery with a focus on interhospital collaboration in the United States to improve stroke performance measures specific to stroke center certification. The state of Kentucky's experience and utilization of the Institute for Healthcare Improvement Breakthrough Series model with key strategies for success will be discussed to serve as a foundation and empower novice stroke leaders in learning health systems. The models may be adapted internationally for application to stroke-specific care process improvement locally, regionally, and nationally; among organizations within the same health system or competing systems; and among organizations with funding or without funding to improve stroke performance measures.

Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus.

BACKGROUND: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient). METHODS: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L). RESULTS: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19-99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection. CONCLUSIONS: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.

SARS-CoV-2 infection and seizures: the perfect storm.

Seizures have been increasingly identified as a neurologic manifestation of coronavirus disease 2019 (COVID-19) infection. They may be symptomatic due to systemic infections, as a result of direct central nervous system (CNS) invasion, or occur in response to inflammatory reactions to the virus. It is possible that proinflammatory molecules released in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to hyperexcitability and epileptogenesis, similar to infections caused by other neurotrophic viruses. Cerebral spinal fluid (CSF) in patients with COVID-19 and seizures is negative for SARS-CoV-2 (PCR) in the majority of patients, but has been found to be positive for proinflammatory molecules like IL-6, IL-8, and anti-neuronal autoantibodies. Electroencephalogram (EEG) in COVID-19 patients are nonspecific. However, in the encephalopathic and critically ill subpopulation, EEG is essential in detecting nonconvulsive seizures and status epilepticus which is associated with increased overall mortality in COVID-19 patients. Thus, as encephalopathy is often the only CNS symptom evidenced in patients with nonconvulsive seizures, more judicious use of continuous EEG in encephalopathic COVID-19 patients should be considered. This would facilitate earlier detection and treatment of seizures in this population, which would ultimately improve outcomes. Further research into the onset and potential for development of seizures and epilepsy in patients with COVID-19 is needed.

Care of the Patient With Acute Ischemic Stroke (Prehospital and Acute Phase of Care): Update to the 2009 Comprehensive Nursing Care Scientific Statement: A Scientific Statement From the American Heart Association.

The year 2020 was the year of the nurse, celebrating nurse scholarship, innovation, and leadership by promoting scientific nursing research, improving nursing practice, advancing nursing education, and providing leadership to influence health policy. As architects of stroke care, neuroscience nurses play a vital role in collaborating and coordinating care between multiple health professionals. Nurses improve accessibility and equity through telestroke, emergency medical services, and mobile stroke units and are integral to implementing education strategies by advocating and ensuring that patients and caregivers receive stroke education while safely transitioning through the health care system and to home. Stroke care is increasingly complex in the new reperfusion era, requiring nurses to participate in continuing education while attaining levels of competency in both the acute and recovery care process. Advanced practice nurses are taking the lead in many organizations, serving as prehospital providers on mobile stroke units, participating as members of the stroke response team, and directing stroke care protocols in the emergency department. This scientific statement is an update to the 2009 "Comprehensive Overview of Nursing and Interdisciplinary Care of the Acute Ischemic Stroke Patient." The aim is to provide a comprehensive review of the scientific evidence on nursing care in the prehospital and hyperacute emergency hospital setting, arming nurses with the necessary tools to provide evidenced-based high-quality care.

Hospital outcomes of acute COVID-19 infection among patients with neurological conditions: a single-center study.

Background: Coronavirus disease 2019 (COVID-19) infection has been associated with severe neurological consequences, including stroke or seizures, and less severe neurological sequelae, including headaches, dizziness, and anosmia. Earlier COVID-19 variants were associated with high morbidity and mortality; however, knowledge of the impact of neurological conditions in the setting of COVID-19 on healthcare outcomes is limited. We sought to determine the impact of acute neurological conditions and acute COVID-19 infection on inpatient hospitalization outcomes. Methods: This was a retrospective, observational study of adult patients who were admitted to a large academic medical center in the Southeastern US between April 2020 and December 2021 with acute COVID-19 infection and a neurological diagnosis. Patient demographics, medical history, neurological diagnoses, and hospitalization outcomes were obtained from the medical record. Descriptive statistics and unadjusted and adjusted logistic regression analyses were performed. Results: Of the 1,387 patients included in this study, 27% died and 23% were kept under ventilation during hospitalization. The mean +/- standard deviation (SD) age was 64.6+/-16.9 years, with 52.8% women and 30.1% identifying as Black/African American. The most common neurological conditions included ischemic stroke (35.0%), movement disorder (12.0%), and hemorrhagic stroke (10.7%). In-hospital death was most common among those with epilepsy (p = 0.024), headache (p = 0.026), and dementia (p < 0.0001) compared to individuals without those conditions. Ventilation support was given more commonly to dementia patients (p = 0.020). Age was a significant risk factor for death (p < 0.001) and hospital length of stay (LOS) for ventilation (p < 0.001), but no neurological condition was a significant factor in adjusted logistic regression analyses. Discussion: Mortality was high in this study, with more than one-quarter of patients dying in the hospital. Death was the most common among those with epilepsy, headache, or dementia, but no neurological condition increased the risk of in-hospital mortality or ventilation. Future studies would determine the long-term neurological sequelae of those discharged from the hospital with COVID-19 and a neurological condition.

Stroke: Hospital Nursing Management Within the First 24 Hours.

Within the United States, someone will have a stroke approximately every 40 seconds. Eighty-five percent of strokes are ischemic, with 15% classified as either intracranial or subarachnoid hemorrhage. Stroke care is complex, and nurses play a critical role in identification, assessment, management, and coordination throughout the stroke continuum of care. This article will explore the nursing care of the patient with ischemic and hemorrhagic stroke during the first 24 hours.

Comparison of Outcomes of Ischemic Stroke Initially Imaged With Cranial Computed Tomography Alone vs Computed Tomography Plus Magnetic Resonance Imaging.

Importance: Patients with acute ischemic stroke often undergo magnetic resonance imaging (MRI) in addition to computed tomography (CT), but its association with clinical outcomes is uncertain. Objective: To assess whether clinical outcomes of patients with acute ischemic stroke with initial CT alone were noninferior to those with additional MRI. Design, Setting, and Participants: A retrospective observational propensity score-matched cohort study of clinical outcomes at discharge and 1 year for patients hospitalized with acute ischemic stroke was conducted at an academic medical center between January 2015 and December 2017. Data collection from an electronic medical record system performed from May 2020 through January 2022 was not completely blinded. Noninferiority margins were based on the designs of previous randomized clinical trials of ischemic stroke treatments. Statistical analysis was performed in January 2022. Participants were adults hospitalized with acute ischemic stroke with admission diagnosis based on CT. Exclusion criteria were primarily missing data. From 508 eligible patients, all 123 cases with additional MRI were propensity-score matched to 123 controls without. Exposure: MRI after initial diagnosis. Main Outcomes and Measures: Death or dependence at hospital discharge (modified Rankin Scale score of 3-6) and stroke or death occurring in survivors within 1 year after discharge. Results: Among 246 participants, the median age was 68 years (IQR, 58-78.8 years) and 131 (53.0%) were men. Death or dependence at discharge occurred more often in patients with additional MRI (59 of 123 [48.0%]) than in those with CT alone (52 of 123 [42.3%]; absolute difference, 5.7%; 95% CI, -6.7% to 18.1%), meeting the -7.50% criterion for noninferiority. Stroke or death within 1 year after discharge determined for 225 of 235 (96%) survivors occurred more often in patients with additional MRI (22 of 113 [19.5%]) than in those with CT alone (14 of 112 [12.5%]; relative risk, 1.14; 95% CI, 0.86-1.50), meeting the 0.725 relative risk criterion for noninferiority. Conclusions and Relevance: This propensity score-matched cohort study of patients hospitalized with acute ischemic stroke found that a diagnostic imaging strategy of initial CT alone was noninferior to initial CT plus additional MRI with regard to clinical outcomes at discharge and at 1 year. Further research is needed to determine which patients hospitalized with acute ischemic stroke benefit from MRI.

Phase I studies of interleukin (IL)-2 and rituximab in B-cell non-hodgkin's lymphoma: IL-2 mediated natural killer cell expansion correlations with clinical response.

PURPOSE: Expansion and activation of natural killer (NK) cells with interleukin-2 (IL-2) may enhance antibody-dependent cellular cytotoxicity (ADCC), an important mechanism of rituximab activity. Two parallel Phase I studies evaluated combination therapy with rituximab and IL-2 in relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). EXPERIMENTAL DESIGN: Thirty-four patients with advanced NHL received rituximab (375 mg/m(2) i.v. weekly, weeks 1-4) and escalating doses of s.c. IL-2 [2-7.5 MIU daily (n = 19) or 4.5-14 million international units three times weekly (n = 15), weeks 2-5]. Safety, tolerability, clinical responses, NK cell counts, and ADCC activity were evaluated. RESULTS: Maximally tolerated doses (MTD) of IL-2 were 6 MIU daily and 14 million international units thrice weekly. The most common adverse events were fever, chills, and injection site reactions. Dose-limiting toxicities were fatigue and reversible liver enzyme test elevations. Of the 9 patients enrolled at the daily schedule MTD, 5 showed clinical response. On the thrice-weekly schedule at the MTD, 4 of 5 patients responded. Responders showed median time to progression of 14.9 and 16.1 months, respectively, for the two studies. For the same total weekly dose, thrice-weekly IL-2 administration induced greater increases in NK cell counts than daily dosing, and NK cells correlated with clinical response on the thrice-weekly regimen. ADCC activity was increased and maintained after IL-2 therapy in responding and stable disease patients. CONCLUSIONS: Addition of IL-2 to rituximab therapy is safe and, using thrice-weekly IL-2 dosing, results in NK cell expansion that correlates with response. This combination treatment regimen merits additional evaluation in a randomized clinical trial.

Anti-inflammatory approaches that target the chemokine network.

Chemokine-ligand/receptor axes play pivotal roles in a myriad of inflammatory, allergic and autoimmune diseases, as well as in the promotion of tumor growth and metastasis. Upon insult, tissue resident cells (and cancer cells in general) release a defined set of inflammatory chemokines that are responsible for the recruitment of activated pathological leukocytes. Recruited leukocytes synthesize and release a host of inflammatory mediators such as chemokines, cytokines, reactive oxygen and nitrogen species, and proteinases. These agents are responsible for the maintenance and amplification of inflammatory responses, and are directly responsible for secondary tissue damage, promotion of autoimmunity, fibrosis and tissue remodelling. Many cancers are associated with the expression of chemokine ligands that co-opt leukocytes such as tumor associated macrophages which in turn provide mediators including growth factors, chemokines and proteinases that promote angiogenesis, tumor growth, and cancer metastasis. Here, we discuss the relevant patents, development and the mechanism of action of a range of therapeutic and potential therapeutic agents that specifically target the chemokine ligand and receptor network. The main approaches that will be highlighted here are antagonism, cell depletion and the relatively unexplored fields of anti-sense, gene and stem cell therapies.

Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma.

Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.

Synergistic anti-tumor responses after administration of agonistic antibodies to CD40 and IL-2: coordination of dendritic and CD8+ cell responses.

In cancer, the coordinate engagement of professional APC and Ag-specific cell-mediated effector cells may be vital for the induction of effective antitumor responses. We speculated that the enhanced differentiation and function of dendritic cells through CD40 engagement combined with IL-2 administration to stimulate T cell expansion would act coordinately to enhance the adaptive immune response against cancer. In mice bearing orthotopic metastatic renal cell carcinoma, only the combination of an agonist Ab to CD40 and IL-2, but neither agent administered alone, induced complete regression of metastatic tumor and specific immunity to subsequent rechallenge in the majority of treated mice. The combination of anti-CD40 and IL-2 resulted in significant increases in dendritic cell and CD8(+) T cell number in advanced tumor-bearing mice compared with either agent administered singly. The antitumor effects of anti-CD40 and IL-2 were found to be dependent on CD8(+) T cells, IFN-gamma, IL-12 p40, and Fas ligand. CD40 stimulation and IL-2 may therefore be of use to promote antitumor responses in advanced metastatic cancer.

Tratamiento de la infeccion temprana por VIH-1 en adultos / Management of early HIV-1 infection in adults

Si una persona sospecha que esta infectada con el virus de la inmunodeficiencia humana (VIH-1) probablemente buscara la ayuda de un medico general; por lo tanto es importante que los medicos generales esten preparados para atender a tales pacientes. Los autores de este articulo explican como se diferencia la infeccion por VIH-1 de otros trastornos que puedan tener manifestaciones similares, recalcan la importancia de remitir a los pacientes a centros asistenciales especializados y comentan las mejores formas de suprimir la infeccion a largo plazo