Evidence-Based Recommendations for Education Provided to Patients and Families Regarding the Adverse Events of ALK and MEK Inhibitors: A Systematic Review From the Children's Oncology Group.

Background: Pediatric oncology patients receive multiple modalities of therapy to treat their malignancies. These modalities have the potential for acute toxicity and late effects. In the last decade, a new modality known as targeted biological therapy, has become an integral part of treatment for pediatric cancers. As targeted therapy use has increased, adverse events specific to these targeted agents have emerged, requiring a new effort focused on providing education to patients and families regarding how best to report, monitor, and manage these adverse events. Method: A clinical question was developed to guide the systematic literature review. Anaplastic lymphoma kinase (ALK) and mitogen-activated protein kinase kinase (MEK) inhibitors were selected for review due to their frequency of use in pediatric oncology. The search was conducted to identify relevant articles published between January 1, 2000 and May 5, 2020. Articles were screened by two team members for inclusion/exclusion criteria using the web-based systematic review tool, Rayyan. Results: Twenty-seven articles met the eligibility criteria for inclusion and were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation criteria. Adverse events for ALK and MEK inhibitors included manifestations of the gastrointestinal, hematologic, dermatologic, musculoskeletal, neurological, cardiovascular, and ocular systems. Recommendations for patient/family education were made for ALK and MEK inhibitors based on the reported adverse events. Conclusions: Adverse events of ALK and MEK inhibitors differ from the more common adverse events experienced with conventional treatment modalities used in pediatric oncology. It is important for nurses to include information regarding potential adverse events in patient/family education for children receiving these targeted agents.

Reflections on the Past Decade in Evidence-Based Practice Within the Children's Oncology Group.

Background: The Children's Oncology Group (COG) is the only National Cancer Institute-supported clinical trials organization focused exclusively on childhood and adolescent cancer research. The COG Nursing Discipline Committee has embedded the tenets of evidence-based practice (EBP) into clinical trials nursing in order to standardize the nursing care delivered to children enrolled on these trials. The COG nursing EBP initiative is aimed at developing evidence-based clinical resources and tools to provide guidance to clinicians regarding topics relevant to the provision of cancer treatment for patients enrolled on COG clinical trials from diagnosis through survivorship. A rigorous, evidence-based process designed to guide development of the evidence-based clinical tools and resources within the COG nursing discipline was developed and was implemented with the first nurse expert team beginning in 2012. Method: The standardized process included (a) selecting EBP projects and nursing expert teams (NETs), (b) providing leadership, mentoring, and championship for NETs; (c) approving clinical content developed through the NETs; and (d) providing guidance and oversight over planned dissemination of the COG EBP projects. Results: The COG Nursing EBP Subcommittee has developed 15 publications to date that include 90 authors. Eleven of these authors contributed to multiple publications. Discussion: On this 10th anniversary of the development of the EBP within the COG nursing discipline, we recognize its contributions to the professional growth of many of the discipline's members and to advances in nursing care for children enrolled in pediatric cancer clinical trials.

Feasibility of a universal suicidality tool for adolescents.

BACKGROUND: The suicide rate among adolescents has been increasing rapidly over the past several years. LOCAL PROBLEM: Adequate screening for suicide risk in this population, particularly youth of color, is lacking. METHODS: The Ask Suicide-Screening Questions (ASQ) tool was implemented at two adolescent-focused health clinics in a large U.S. city. INTERVENTIONS: This project followed the Ottawa Model of Research Use. Participating clinicians were surveyed before and after receiving an educational module on suicide risk screening, the ASQ tool, and clinical pathways. Clinicians were also asked about the feasibility and acceptability of the ASQ tool in their practice. An electronic medical records software was used to gather data on patients newly screened for suicide risk using the ASQ tool. RESULTS: Among eligible patients, 40.2% were screened using the ASQ tool during the 4-month duration of the project. Most clinicians reported that using the tool was feasible within their practice (66%) and 100% endorsed its acceptability (i.e., reporting that they were comfortable screening for suicide and that the ASQ was easy to use). CONCLUSIONS: The ASQ may be a promising screening tool for clinicians to use to address the mental health needs of at-risk youth. This project supports the universal acceptability and feasibility of its use in inner-city primary care clinics.

Facilitating and Implementing a Process for the Delivery of Pediatric Oncology New Diagnosis Education Among Nursing Staff Through the Electronic Medical Record.

Background: An estimated 11,060 children between the ages of 1 and 14 years and 4,900 adolescents between the ages of 15 and 19 years are diagnosed with cancer in the United States. Parents with children newly diagnosed with cancer must acquire new knowledge related to the diagnosis, treatment plan, psychosocial care, and home management therapies to safely provide care following discharge. Expert consensus and review of current evidence demonstrate that utilizing a new diagnosis education checklist allows the delivery of essential information to patients and caregivers. The checklist divides educational topics into three sections: primary, secondary, and tertiary topics. This project followed the completion of an evidence-based fellowship through Children's Oncology Group focusing upon the feasibility and efficacy of implementing a standardized new diagnosis education checklist. The fellowship identified secondary topic documentation and an electronic medical record (EMR) checklist as areas of future work. Methods: This quality improvement project focused upon nursing staffs' documentation of secondary topics and the development/utilization of an EMR checklist. A pre-post survey design evaluated the outcomes of secondary topic documentation and EMR checklist implementation. Results: This nurse-led initiative created templates for primary and secondary topic checklists using Epic's SmartPhrase feature ".PHOPTED1" and ".PHOPTED2." Secondary topic completion and documentation increased 26% following implementation, and over 40% of the nursing staff indicated that they were very likely to continue to use the new templates. Discussion: Project templates are readily applicable to institutions that utilize Epic. Template examples and strategies to facilitate inpatient/outpatient checklist completion are discussed.

Long-term effects of spasticity treatment, including selective dorsal rhizotomy, for individuals with cerebral palsy.

AIM: To understand the long-term effects of comprehensive spasticity treatment, including selective dorsal rhizotomy (SDR), on individuals with spastic cerebral palsy. METHOD: This was a pre-registered, multicenter, retrospectively matched cohort study. Children were matched on age range and spasticity at baseline. Children at one center underwent spasticity treatment including SDR (Yes-SDR, n=35) and antispastic injections. Children at two other centers had no SDR (No-SDR, n=40 total) and limited antispastic injections. All underwent subsequent orthopedic treatment. Participants returned for comprehensive long-term assessment (age ≥21y, follow-up ≥10y). Assessment included spasticity, contracture, bony alignment, strength, gait, walking energy, function, pain, stiffness, participation, and quality of life. RESULTS: Spasticity was effectively reduced at long-term assessment in the Yes-SDR group and was unchanged in the No-SDR group. There were no meaningful differences between the groups in any measure except the Gait Deviation Index (Yes-SDR + 11 vs No-SDR + 5) and walking speed (Yes-SDR unchanged, No-SDR declined 25%). The Yes-SDR group underwent more subsequent orthopedic surgery (11.9 vs 9.7 per individual) and antispastic injections to the lower limbs (14.4 vs <3, by design). INTERPRETATION: Untreated spasticity does not cause meaningful impairments in young adulthood at the level of pathophysiology, function, or quality of life.

Evidence-Based Recommendations for Nurse Monitoring and Management of Immunotherapy-Induced Cytokine Release Syndrome: A Systematic Review from the Children's Oncology Group.

Children with B-precursor acute lymphoblastic leukemia and B-cell lymphoma, particularly those with relapsed or refractory disease, are increasingly enrolled on phase II and phase III clinical trials studying immunotherapies. These therapeutic agents may be associated with a high risk of cytokine release syndrome (CRS), and nurses lack standardized guidelines for monitoring and managing patients with CRS. Six studies and one clinical practice guideline were included in this systematic review that examined the evidence of CRS following administration of chimeric antigen receptor T-cell therapy or the bi-specific T-cell engager antibody, blinatumomab. Six nursing practice recommendations (five strong, one weak) were developed based on low or very low-quality evidence: three reflect preinfusion monitoring, one focuses on monitoring during and postinfusion, and three pertain to the nurse's role in CRS management.

Long-term functional outcomes after an external femoral derotation osteotomy in individuals with cerebral palsy.

BACKGROUND: It is unknown how a femoral derotation osteotomy (FDO) during childhood affects functional outcomes in adulthood among individuals with bilateral cerebral palsy (CP). RESEARCH QUESTIONS: How do long-term functional outcomes after an FDO compare to matched individuals who did not have an FDO? How do outcomes change over time? METHODS: We queried the gait laboratory database for individuals who underwent an external FDO in childhood and were currently ≥25 years old. Participants returned for a long-term analysis (gait, physical examination, functional tests, imaging, questionnaires). The matched non-FDO group included only individuals in Gross Motor Function Classification System levels I-II, yielding three groups (non-FDO I-II, FDO I-II, FDO III-IV). RESULTS: Sixty-one adults (11 non-FDO, 34 FDO I-II, 16 FDO III-IV) returned 13-25 years after baseline (non-FDO) or surgery (FDO). The non-FDO and FDO I-II groups were matched at baseline on most variables, except the FDO group had weaker hip abductors. At long-term, groups were similar on gait variables (median long-term hip rotation [primary outcome], non-FDO: -4°, FDO I-II: -4°, FDO III-IV: -5°), hip abduction test, fear of falling, and most pain measures despite anteversion being 29° greater in the non-FDO group. The FDO I-II group reported more falls than the non-FDO group. All groups improved on hip rotation, foot progression, and hip abductor strength. Speed and step length decreased/tended to decrease for all three groups. Hip abduction moment and gait deviation index did not change. Improvements in the FDO groups were maintained from short- to long-term. SIGNIFICANCE: These results challenge the notion that an FDO is necessary to correct mean stance hip rotation for higher functioning individuals since nearly identical results were achieved by adulthood in the non-FDO I-II group. However, an FDO provides improvement earlier and maintenance from short- to long-term. This should factor into the shared decision-making process.

Implementing and Evaluating a Standardized New Diagnosis Education Checklist: A Report From the Children's Oncology Group.

When a child is newly diagnosed with cancer, parents report feeling overwhelmed with the amount of information that they must process in order to safely care for their child at home. The Children's Oncology Group (COG) Nursing Discipline has focused on examining current practices for educating families of children newly diagnosed with cancer, and developing tools to enhance the process of patient/family education at the time of diagnosis, including development of a COG Standardized Education Checklist, which classifies education into primary, secondary, and tertiary topics. The COG Nursing Discipline awarded nursing fellowships to two doctorally prepared nurses practicing at two distinct COG institutions to evaluate the checklist implementation. This project addressed the primary topics on the checklist essential to safely care for the child at home following the first hospital discharge. Checklist feasibility was determined by the proportion of checklists completed. Checklist fidelity was determined by review of documentation on the checklist regarding educational topics covered, learner preferences, and methods used. Checklist acceptability was assessed through parent/caregiver and nurse feedback. Project implementation occurred over a 5-month period and involved 69 newly diagnosed families. Implementation of the checklist was feasible (81%), with moderate fidelity to checklist topics taught across the two sites. Verbal instruction and written documentation were the most prevalent form of education. The return rate for the parent/caregiver and nurse acceptability questionnaires was moderate to low (68% and 12%, respectively), parent/caregiver feedback was positive and acceptability among responding nurses was high, with 92% of nurses identifying the primary checklist as useful.

Acute safety, efficacy, and advantages of a novel cryoballoon ablation system for pulmonary vein isolation in patients with paroxysmal atrial fibrillation: initial clinical experience.

AIMS: Cryoballoon pulmonary vein isolation (PVI) is a safe and effective treatment for atrial fibrillation (AF). Current limitations include incomplete vein occlusion due to balloon rigidity and inconsistent electrogram recording, which impairs identification of isolation. We aimed to evaluate the acute safety and performance of a novel cryoballoon system. METHODS AND RESULTS: The system includes a steerable sheath, mapping catheter, and a balloon that maintains uniform inflation pressure and size following initiation of ablation. Protocol-directed cryoablation was delivered for 180 s for isolation documented in ≤60 s, otherwise freeze duration was 240 s. Primary endpoints were acute safety and vein isolation. Pulmonary vein isolation was confirmed at ≥30 min post-isolation. Data were compared across vein locations. Thirty patients with paroxysmal AF were enrolled at two centres and underwent PVI. Pulmonary vein isolation was achieved with cryoablation only in 100% of veins (120/120). Nadir temperature was -53.1 ± 5.3°C. The number of applications to achieve PVI was 1.4 ± 0.4 per vein. Of the 120 veins, 89 were isolated with a single cryothermal application (10/30 patients required only 4 total cryoablations). There were no procedural- or device-related serious adverse events at 30 days post-procedure. A subset (24/30) of patients was followed for 1-year and 71% (17/24) remained free of atrial arrhythmias. Six patients with arrhythmia recurrence were remapped and three had durable PVI for all four veins. CONCLUSION: In this first human experience, the novel cryoballoon platform was safe, efficacious, and demonstrated a high proportion of successful single ablation isolation.

Commonly Reported Adverse Events Associated With Pediatric Immunotherapy: A Systematic Review From the Children's Oncology Group

BACKGROUND: Immunotherapy is a new and promising approach to treating pediatric cancers. These types of therapies have unique mechanisms of action for identifying and fighting cancer, as compared with traditional chemotherapy, and therefore are associated with different therapy-related adverse events (AEs). The purpose of this systematic review was to review available evidence to: (a) identify commonly reported AEs associated with immunotherapy agents frequently used in pediatric oncology and (b) generate recommendations for nursing practice. METHOD: A clinical question was developed and used to guide the systematic literature review. Five immunotherapy agents (dinutuximab, blinatumomab, rituximab, inotuzumab ozogamicin, brentuximab vedotin) were selected for inclusion secondary to their high relevance to pediatric oncology. A literature search was conducted to locate articles published between January 1, 2003 and October 31, 2018. RESULTS: Seventeen articles met eligibility criteria for inclusion and were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation criteria. The most commonly reported AEs for the selected immunotherapy agents were identified and summarized. Strong recommendations are made for nurses to become familiar with the unique AE profiles associated with individual immunotherapy agents. Agent-specific recommendations for nursing practice regarding AEs associated with dinutuximab and rituximab were generated. CONCLUSIONS: Immunotherapy is rapidly emerging as an effective therapy for pediatric cancers. Nurses need to be aware of the breadth of agent-specific, immunotherapy-related AEs to appropriately monitor and manage patients receiving these therapies. Additional work is needed to confidently profile immunotherapy-related AEs in pediatric oncology and to develop agent-specific educational materials for patients/families.

Participant-level characteristics differ by recruitment setting when evaluating a behavioral intervention targeting adolescents with asthma.

OBJECTIVE: The recruitment setting plays a key role in the evaluation of behavioral interventions. We evaluated a behavioral intervention for urban adolescents with asthma in three randomized trials conducted separately in three different settings over the course of 8 years. We hypothesized that characteristics of trial participants recruited from the ED and clinic settings would be significantly different from that of youth participating in the school-based trials. The intervention evaluated was Puff City, a web-based program that uses tailoring to improve asthma management behaviors. METHODS: The present analysis includes youth aged 13-19 years who reported a physician diagnosis of asthma and symptoms at trial baseline. In the three trials, all participants were randomized post-baseline to a web-based, tailored intervention (treatment) or generic web-based asthma education (control). RESULTS: Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (p < 0.001) and more caregiver depression (p < 0.001). Clinic-based participants were more likely to have computer/ internet access than participants from the school-based trial (p < 0.001). Both ED and clinic participants were more likely to report controller medication (p's < 0.001) and higher teen emotional support (p's < 0.01) when compared to the schools, but were less likely to report Medicaid (p's < 0.014) and exposure to environmental tobacco smoke (p < 0.001). CONCLUSION: Compared to participants in the school-based trials, participants recruited from ED and clinic settings differed significantly in terms of healthcare use, as well as psychosocial and sociodemographic factors. These factors can inform intervention content, and may impact external validity of behavioral interventions for asthma.

Impact of specific preclinical variables on coagulation biomarkers in cancer-associated thrombosis.

Coagulation biomarkers are being actively studied for their diagnostic and prognostic value in patients with venous thromboembolism and cancer, as well as in the study of pathogenic mechanisms between cancer and thrombosis. For the results of such studies to be accurate and reproducible, attention must be paid to minimize sources of error in all phases of testing. The pre-analytical phase of laboratory testing is known to be fraught with the majority of errors. Coagulation testing is particularly susceptible to conditions during collection, processing, transport and storage of specimens which can lead to clinically significant errors in results. In addition, changes in pre-analytical conditions can impact different biomarkers differently. Therefore, research studies investigating coagulation biomarkers must carefully standardize not just the analytical phase, but also the pre-analytical phase of testing to ensure accuracy and reliability. We briefly review the impact of pre-analytical conditions on coagulation testing in general, and on specific biomarkers in cancer and thrombosis. In addition, we provide recommendations to reduce pre-analytical errors by developing and sharing standard operating procedures that specifically target standardization of methodologies for collecting specimens and measuring current and emerging coagulation biomarkers in cancer studies.

Alcohol use is not a significant contributor to myelodysplastic syndromes.

PURPOSE: Myelodysplastic syndromes (MDS) are a class of clonal neoplastic disorders of largely unknown etiology, and published data remain inconclusive regarding the association between lifetime alcohol consumption and MDS risk. In these analyses, data from a population-based case-control study were used to investigate this association. METHODS: Eligible cases of MDS were identified through the Minnesota Cancer Reporting System; controls were matched by sex and age-decile. A central review process was used to confirm MDS diagnosis and classify subtypes. Unconditional and polytomous logistic regression were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Kaplan-Meier curves were used to compare survival by category of lifetime alcohol consumption. RESULTS: In total, 398 cases of MDS and 698 controls were included. Alcohol consumption at 23-30, 31-49, and 50-65 years of age, recent consumption 1 year before diagnosis/interview, and lifetime consumption were not found to be significantly associated with MDS in males (OR range 0.63-0.99) or females (OR range 0.58-1.70). Analysis by MDS subtype further suggested there was not a significant association between recent alcohol consumption and odds of disease by subtype (OR range 0.39-1.13). Lifetime alcohol consumption was not significantly associated with survival after diagnosis of MDS CONCLUSIONS: Previously reported associations between alcohol consumption and MDS risk were inconsistent. Results from our analyses by sex and disease subtype do not support alcohol as a significant contributor to risk of MDS.

Evidence-Based Recommendations for the Appropriate Level of Sedation to Manage Pain in Pediatric Oncology Patients Requiring Procedures: A Systematic Review From the Children's Oncology Group [Formula: see text].

Repeated invasive and painful procedures are often necessary components of pediatric cancer treatment. Adequate pain control during procedures is essential; however, procedure-related pain may be underestimated and undertreated. Currently, there is not a standard approach for the appropriate level of sedation to manage procedure-related pain in children with cancer. A team was assembled to review the evidence and develop recommendations to determine the appropriate level of sedation necessary for pain control in patients undergoing pediatric oncology procedures. After a systematic search of the literature, 15 research-based articles were synthesized and critically appraised. A recommendation was made related to the level of sedation utilized for bone marrow aspirates and bone marrow biopsies. There is a need for further research related to the necessary level of sedation for patients undergoing pediatric oncology procedures.

Perspectives on Cancer Pain Assessment and Management in Children.

OBJECTIVE: To report evidence regarding pain assessment and management for children and adolescents receiving treatment for cancer. DATA SOURCES: Published research and clinical guidelines. CONCLUSION: Children and adolescents experience multiple sources of pain across the cancer continuum. They require developmentally relevant approaches when assessing and managing pain. This review suggests that consideration of the developmental stage and age of the child are essential in both pain assessment and pain management. IMPLICATIONS FOR NURSING PRACTICE: Pediatric oncology nurses play a key role in developmentally appropriate pain assessment, identification of potential strategies to manage pain, and delivery of pharmacologic and nonpharmacologic therapies.

A computational solution to improve biomarker reproducibility during long-term projects.

Biomarkers are fundamental to basic and clinical research outcomes by reporting host responses and providing insight into disease pathophysiology. Measuring biomarkers with research-use ELISA kits is universal, yet lack of kit standardization and unexpected lot-to-lot variability presents analytic challenges for long-term projects. During an ongoing two-year project measuring plasma biomarkers in cancer patients, control concentrations for one biomarker (PF) decreased significantly after changes in ELISA kit lots. A comprehensive operations review pointed to standard curve shifts with the new kits, an analytic variable that jeopardized data already collected on hundreds of patient samples. After excluding other reasonable contributors to data variability, a computational solution was developed to provide a uniform platform for data analysis across multiple ELISA kit lots. The solution (ELISAtools) was developed within open-access R software in which variability between kits is treated as a batch effect. A defined best-fit Reference standard curve is modelled, a unique Shift factor "S" is calculated for every standard curve and data adjusted accordingly. The averaged S factors for PF ELISA kit lots #1-5 ranged from -0.086 to 0.735, and reduced control inter-assay variability from 62.4% to <9%, within quality control limits. S factors calculated for four other biomarkers provided a quantitative metric to monitor ELISAs over the 10 month study period for quality control purposes. Reproducible biomarker measurements are essential, particularly for long-term projects with valuable patient samples. Use of research-use ELISA kits is ubiquitous and judicious use of this computational solution maximizes biomarker reproducibility.

The Biospecimen Preanalytical Variables Program: A Multiassay Comparison of Effects of Delay to Fixation and Fixation Duration on Nucleic Acid Quality.

CONTEXT.­: Despite widespread use of formalin-fixed, paraffin-embedded (FFPE) tissue in clinical and research settings, potential effects of variable tissue processing remain largely unknown. OBJECTIVE.­: To elucidate molecular effects associated with clinically relevant preanalytical variability, the National Cancer Institute initiated the Biospecimen Preanalytical Variables (BPV) program. DESIGN.­: The BPV program, a well-controlled series of systematic, blind and randomized studies, investigated whether a delay to fixation (DTF) or time in fixative (TIF) affects the quantity and quality of DNA and RNA isolated from FFPE colon, kidney, and ovarian tumors in comparison to case-matched snap-frozen controls. RESULTS.­: DNA and RNA yields were comparable among FFPE biospecimens subjected to different DTF and TIF time points. DNA and RNA quality metrics revealed assay- and time point-specific effects of DTF and TIF. A quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was superior when assessing RNA quality, consistently detecting differences between FFPE and snap-frozen biospecimens and among DTF and TIF time points. RNA Integrity Number and DV200 (representing the percentage of RNA fragments longer than 200 nucleotides) displayed more limited sensitivity. Differences in DNA quality (Q-ratio) between FFPE and snap-frozen biospecimens and among DTF and TIF time points were detected with a qPCR-based assay. CONCLUSIONS.­: DNA and RNA quality may be adversely affected in some tumor types by a 12-hour DTF or a TIF of 72 hours. Results presented here as well as those of additional BPV molecular analyses underway will aid in the identification of acceptable delays and optimal fixation times, and quality assays that are suitable predictors of an FFPE biospecimen's fit-for-purpose.

Implementation of a Survivorship Care Plan Program in a Community-Based Oncology Clinic.

There is conflicting evidence from the small number of randomized controlled trials (RCTs) that have assessed the benefit of survivorship care plans (SCPs) on improving patient outcomes. Yet, published quasi-experimental and descriptive studies provide preliminary evidence suggesting that using survivorship care plans in practice may improve patient knowledge, decrease worry and anxiety, and lead to patient and primary care physician satisfaction. Given the conflicting evidence and the paucity of RCTs, further research is needed to more fully explore the effect of SCP on patient outcomes. To address this knowledge gap, an SCP program was implemented in a community-based oncology clinic and used quality improvement methodology to assess the effect on patient knowledge of diagnosis, treatment, and follow-up, and to understand patients' satisfaction with the current SCP program. A total of 30 cancer patients were recruited in Southeast Michigan to participate in an SCP quality improvement project and completed surveys to evaluate the SCP program. Data were collected between December 2017 and March 2018. We observed a statistically significant (p = .028) difference between pre- and postintervention (survivorship care plan visit) knowledge scores about cancer diagnosis, treatment received, and follow-up recommendations. Moreover, participants were satisfied with the survivorship care plan and visit.

Neurokinin-1 Receptor Deficiency Improves Survival in Murine Polymicrobial Sepsis Through Multiple Mechanisms in Aged Mice.

OBJECTIVE: Substance P (SP) is a neuropeptide that contributes to a proinflammatory state by binding to the neurokinin 1 receptor (NK-1R). Limiting this interaction has been shown to attenuate the acute inflammation. Our hypothesis was that NK-1R activation would contribute to the morbidity and mortality of sepsis in a model using mice genetically deficient in the NK-1R. METHODS: To investigate the role of the SP/NK-1R axis in a murine model of sepsis, cecal ligation and puncture (CLP) in NK-1R deficient and wild type (WT) aged mice was performed. Acute inflammation was assessed by measuring circulating cytokines and clinical parameters. RESULTS: Deletion of the NK-1R results in improved survival following CLP (NK-1R knockout mice survival = 100% vs. WT = 14%). A reduction in the inflammatory cytokines interleukin (IL) 6, macrophage inflammatory peptide 2, and IL-1 receptor antagonist, improved hemodynamic parameters, and increased neutrophilia were present in the NK-1R-deficient mice after CLP compared with WT mice. CONCLUSIONS: These data confirm the hypothesis that eliminating the SP/NK-1R interaction in a highly lethal murine model of sepsis leads to decreased morbidity and mortality through multiple mechanisms.