Socialization Into and Through Doctoral Programs in Adapted Physical Activity.

This study examined doctoral students' occupational socialization experiences in U.S. adapted physical activity doctoral programs. Twenty-eight doctoral students were recruited and participated in semistructured, in-depth interviews. Interview transcripts were analyzed through a collaborative qualitative analysis, which resulted in the construction of four themes: (a) early socialization experiences foster a positive, but limited impression of physical education and physical activity; (b) doctoral education is pursued to have a greater impact on the disability community; (c) relationships with socializing agents provide support during doctoral education; and (d) coursework and learning in the community facilitate preparation for faculty roles. The findings indicate that there are several similarities between doctoral students and their peers in other doctoral degree programs. Some of these similarities point to issues that may concern prospective doctoral students and faculty members in adapted physical activity terminal degree programs.

Acute Graft-Versus-Host Disease After Orthotopic Liver Transplantation: Predicting This Rare Complication Using Machine Learning.

Acute graft-versus-host disease (GVHD) is a rare complication after orthotopic liver transplantation (OLT) that carries high mortality. We hypothesized that machine-learning algorithms to predict rare events would identify patients at high risk for developing GVHD. To develop a predictive model, we retrospectively evaluated the clinical features of 1938 donor-recipient pairs at the time they underwent OLT at our center; 19 (1.0%) of these recipients developed GVHD. This population was divided into training (70%) and test (30%) sets. A total of 7 machine-learning classification algorithms were built based on the training data set to identify patients at high risk for GVHD. The C5.0, heterogeneous ensemble, and generalized gradient boosting machine (GGBM) algorithms predicted that 21% to 28% of the recipients in the test data set were at high risk for developing GVHD, with an area under the receiver operating characteristic curve (AUROC) of 0.83 to 0.86. The 7 algorithms were then evaluated in a validation data set of 75 more recent donor-recipient pairs who underwent OLT at our center; 2 of these recipients developed GVHD. The logistic regression, heterogeneous ensemble, and GGBM algorithms predicted that 9% to 11% of the validation recipients were at high risk for developing GVHD, with an AUROC of 0.93 to 0.96 that included the 2 recipients who developed GVHD. In conclusion, we present a practical model that can identify patients at high risk for GVHD who may warrant additional monitoring with peripheral blood chimerism testing.

Human leukocyte antigen eplet mismatching is associated with increased risk of graft loss and rejection after pediatric heart transplant.

BACKGROUND: While mismatching between donor and recipient human leukocyte antigen (HLA) alleles has been associated with increased graft loss in pediatric heart recipients, it is actually the surface amino acid structures, termed eplets, which determine the antigenicity of each HLA molecule. We hypothesized that HLA eplet mismatch analysis is a better predictor of adverse outcomes after pediatric heart transplant than conventional allele mismatch comparison. METHODS: A retrospective review of the Pediatric Heart Transplant Society database identified pediatric heart recipients (<18 years at listing) with complete donor and recipient HLA typing (A, B, and DR). Imputed high-resolution HLA genotypes were entered into HLAMatchmaker software which then calculated the number of eplet mismatches between each donor-recipient pair. Multivariable Cox regression analysis was used to examine associations between allele or eplet mismatching and adverse outcomes. RESULTS: Compared to those with <20 HLA class I eplet mismatches, recipients with 20 or more HLA class I eplet mismatches had an increased risk of graft loss (HR 1.46 [1.01-2.12], p = .049). HLA class I eplet mismatching was also associated with rejection (>20 mismatches: HR 1.30 [1.03-1.65], p = .030), while HLA class II eplet mismatching was associated with specified antibody-mediated rejection (10-20 mismatches: HR 1.57 [1.06-2.34], p = .025; >20 mismatches: HR 3.14 [1.72-5.71], p < .001). Neither HLA class I nor class II allele mismatching was significantly associated with graft loss or rejection. CONCLUSION: Eplet mismatch analysis was more predictive of adverse post-transplant outcomes (including graft loss and rejection) than allele mismatch comparison. Further study, including prospective high-resolution HLA typing, is warranted.

Comparison of dyad versus individual simulation-based training on stress, anxiety, cognitive load, and performance: a randomized controlled trial.

BACKGROUND: Dyad learning has been shown to be an effective tool for teaching procedural skills, but little is known about how dyad learning may impact the stress, anxiety, and cognitive load that a student experiences when learning in this manner. In this pilot study, we investigate the relationship between dyad training on stress, anxiety, cognitive load, and performance in a simulated bradycardia scenario. METHODS: Forty-one fourth-year medical school trainees were randomized as dyads (n = 24) or individuals (n = 17) for an education session on day 1. Reassessment occurred on day 4 and was completed as individuals for all trainees. Primary outcomes were cognitive load (Paas scale), stress (Cognitive Appraisal Ratio), and anxiety levels (abbreviated State-Trait Anxiety Inventory). Secondary outcomes were time-based performance metrics. RESULTS: On day 1 we observed significant differences for change in anxiety and stress measured before and after the training scenario between groups. Individuals compared to dyads had larger mean increases in anxiety, (19.6 versus 7.6 on 80-point scale, p = 0.02) and stress ratio (1.8 versus 0.9, p = 0.045). On the day 4 post-intervention assessment, no significant differences were observed between groups. Secondary outcomes were significant for shorter time to diagnosis of bradycardia (p = 0.01) and time to initiation of pacing (p = 0.04) in the dyad group on day 1. On day 4, only time to recognizing the indication for pacing was significantly shorter for individual training (hazard ratio [HR] = 2.26, p = 0.02). CONCLUSIONS: Dyad training results in lower stress and anxiety levels with similar performance compared to individual training.

The effect of serum pretreatment regimens for the detection of HLA class I antibodies in platelet-refractory patients.

BACKGROUND: Single antigen bead (SAB) assays are used to identify human leukocyte antigen (HLA) antibodies in patients with platelet refractoriness due to HLA Class I alloimmunization. Some laboratories use serum pretreatment regimens to eliminate interference from immunoglobulin M antibodies and complement. These modifications may contribute to interlaboratory variability, which is a recognized problem with the SAB assay. STUDY DESIGN AND METHODS: Five patients' sera were overnight shipped to 12 laboratories in the United States and internationally. Recipients used their lab's SAB procedure to identify HLA Class I antibodies. The resultant mean fluorescence intensity (MFI) data were compared by instrumentation, bead lot, and pretreatment regimens. Laboratory-specific cutoffs for positive antibodies were applied to the results. RESULTS: Interlaboratory variability for MFI values appears to be associated with different pretreatment regimens. The coefficient of variation (CV) of MFI from samples pretreated with ethylenediaminetetraacetic acid, dithiothreitol, or heat inactivation (EDHI) were similar, ranging from 14% to 56% (mean, 22%). For samples with no pretreatment, the CVs were significantly higher than EDHI-treated samples, ranging from 25% to 74% (mean, 39%; 95% confidence interval, 12.10-21.90; p < 0.0001). An intralaboratory comparison of pretreatment regimens confirmed these findings. Some positive antibody specificities present in EDHI-treated samples were negative in corresponding samples with no pretreatment when laboratory-specific cutoffs for positive antibodies were applied. CONCLUSION: Our results show that greater interlaboratory precision can be achieved when samples are pretreated with EDHI as opposed to no pretreatment, likely because these pretreatments eliminate interference from inhibitors. Inhibitors may mask antibodies, leading to missed (or uncalled) specificities when no pretreatment is used.

Response to random apheresis platelets versus HLA-selected platelets versus pooled platelets in HLA-sensitized patients.

BACKGROUND: It is unknown how pooled platelets (PPs) compare to random apheresis platelets (RAPs) when HLA-selected platelets (PLTs) are unavailable for HLA-sensitized patients. The aim of this study was to compare patient responses to RAPs, HLA-selected PLTs, and PPs in HLA-sensitized patients. STUDY DESIGN AND METHODS: This is a single-institution retrospective study of patients from January 2014 to April 2017 with a class I calculated panel-reactive antibody of 60% or more. Response to transfusion was determined by a corrected count increment (CCI) up to 1 hour after completion of transfusion. A CCI of 5 or more was considered successful. RESULTS: Seventy-seven units of RAPs, 412 units of HLA-selected PLT, and 388 units PPs were transfused. Mean CCIs when transfusing RAPs, HLA-selected PLTs, and PPs were 2.82, 11.44, and 4.77, respectively (p < 0.0001). Posttest comparison between RAPs and PPs revealed no significant difference in mean CCI while there was a significant difference between HLA-selected PLTs versus RAPs and HLA-selected PLTs versus PPs. The success rates of RAPs, HLA-selected PLTs, and PPs were 31%, 80%, and 35% respectively. There was no significant association of type of PLT and success rate when comparing RAPs versus PPs (p = 0.51) while there was a significant association between success rate and type of PLT transfusion when comparing HLA-selected PLTs with RAPs and PPs. CONCLUSION: HLA-selected PLTs resulted in higher mean CCIs and more successful transfusions. There was no significant difference in mean CCI or success rate when transfusing RAPs versus PPs to HLA-sensitized patients. Future studies should assess clinical outcomes in HLA-sensitized patients receiving each type of PLT product.

Transfusion-related immunomodulation: gamma irradiation alters the effects of leukoreduction on alloimmunization.

BACKGROUND: Adverse events following blood transfusion include allosensitization and generalized immunosuppression, collectively referred to as transfusion-related immune modulation. We evaluated the immunological effects of red blood cell (RBC) and platelet transfusions on alloantibody responses and on immunoregulatory cells in nonimmunosuppressed patients undergoing cardiovascular surgery. STUDY DESIGN AND METHODS: Patients were randomized to receive standard unmodified (STD), leukoreduced (LR), or leukoreduced and γ-irradiated (LRγ) RBCs. Patients received only apheresis platelets that were in-process LR and were γ-irradiated for the third arm. Nontransfused patients served as controls for the effects of surgery itself on immunologic changes. Antibodies to HLA were assessed with use of solid-phase assays. The effects of transfusion on adaptive and innate immunity were evaluated by assessing T regulatory cells (Tregs) and invariant natural killer T (iNKT) cells. RESULTS: LR of blood products reduced the development of human leukocyte antigen (HLA) alloantibodies, but only in patients without preexisting HLA antibodies. However, if LR blood products were γ-irradiated, HLA antibody production was not reduced. Compared to nontransfused patients, recipients of STD or LR transfusions showed a significant increase in CD4+CD25hi T cells expressing FoxP3 or CTLA4 and also of iNKT cells producing interleukin-4. In contrast, recipients of LRγ blood products showed markedly lower increases in all three cellular assays. CONCLUSION: LR decreased HLA alloantibody production in naïve recipients, but did not reduce the immunosuppressive effects of transfusion. LRγ reduced immunosuppression and was not associated with decreased HLA alloantibody production.

Donor-specific anti-HLA antibody production following pediatric ABO-incompatible heart transplantation.

ABO-i heart transplantation can be performed in infants with end-stage heart failure to increase organ availability. The development of newly detected DSAs is associated with decreased cardiac graft survival, and the effect of ABO-i transplantation on DSA production is unknown. We examined DSA production and rejection frequency in infant recipients of ABO-i and ABO-c heart transplants via a retrospective cohort study of infant heart transplant recipients transplanted at a single pediatric center between January 2004 and November 2014. Patients were included if they were less than 1 year of age at transplant and had a minimum of 6 months follow-up. DSA positivity was examined under two categories, either the lowest level detectable (MFI > 500) or a level presumed to have clinical relevance in our immunogenetics laboratory (MFI > 5000). Of 52 patients, 36 received ABO-c transplants and 16 received ABO-i transplants. Compared to ABO-c recipients, the ABO-i group showed a consistent but statistically non-significant finding of less frequent ndDSA positivity (69.4% ABO-c vs 43.8% ABO-i with MFI >500, P = 0.122; 41.7% ABO-c vs 25% ABO-i with MFI >5000, P = 0.353). Additionally, ABO-i patients were less likely to have any form of rejection (12.5% vs 47.2%, P = 0.027) or acute cellular rejection (6.3% vs 38.9%, P = 0.021). Our data suggest that infants receiving ABO-i heart transplants may be less likely to develop ndDSAs or have rejection compared to same age ABO-c recipients. Larger multicenter studies are needed to confirm results from this single center study.

Implication of antibodies against human leukocyte antigen in simultaneous presentation of fetal and neonatal alloimmune thrombocytopenia and neutropenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal alloimmune neutropenia (NAN) are two rare complications of newborns caused by antibodies against paternal inherited antigens. Human platelet (HPA) and neutrophil antigens (HNA) are the common targets. Human leukocyte antigen (HLA) class I proteins are also expressed on platelets and neutrophils and anti-HLA antibodies have occasionally been implicated in these complications. We report a premature twin infant who presented with severe thrombocytopenia and neutropenia clinically compatible with FNAIT and NAN, from a mother with no identifiable HPA or HNA antibodies, but with very high levels of complement-fixing antibodies against paternal inherited HLA. These antibodies were also detected in the infant. HLA antibodies are commonly present in multiparous women who deliver healthy infants. They can, however, be cytotoxic and cause clinical complications after blood products transfusion (TRALI and becoming refractory to platelets transfusion) and after organ transplantation (allogeneic organ rejection).

Twelve possible strategies for enhancing interprofessional socialisation in higher education: Findings from an interpretive phenomenological study.

The aim of this study was to investigate the interprofessional socialisation experiences of health professional educators (HPEs) across five health science faculties in Perth, Australia. Evidence supported the importance of educators teaching and learning together, although there was minimal evidence with regard to the type of support HPEs received or required in order to socialise interprofessionally within higher education. Interview participants comprised 26 HPEs from various health-related professions across Western Australia. An interpretive phenomenological framework was used to discover the phenomena of interprofessional socialisation. The examination of the data was undertaken via qualitative content analysis with the aid of NVivo 10 software. Content coding led to the development of categories, sub-categories, and then themes. Five themes were identified; however, only one of these themes, "interprofessional socialisation strategies within higher education," is explored within this article. Based on the data within this theme, 12 possible socialisation strategies (formal and informal) were identified for HPEs, which could be implemented within health science faculties, taking into account the organisation's culture and strategic intent towards interprofessional collaboration and education.

Methods for the selection of platelet products for alloimmune-refractory patients.

The ability to efficiently and accurately diagnose the cause(s) of platelet (PLT) refractoriness is paramount in providing effective PLT products for transfusion. Recent advances in methods for detecting and identifying alloantibodies against human leukocyte antigens (HLAs) and human PLT antigens, combined with accurate molecular techniques for HLA typing, have provided a framework for the development of clinical algorithms to support such patients. Alloantibodies may be detected and/or identified by several methods, including complement-dependent cytotoxicity, enzyme-linked immunosorbent assays (ELISA), and microbead-based assays using Luminex or flow cytometry. The primary difference in these assays is the sensitivity of detection and the range of antibody specificities that may be reliably identified. Direct PLT cross-matching to identify compatible PLTs can be accomplished by several methods, including solid-phase red cell adherence, modified antigen capture ELISA, and flow cytometry. A survey of blood centers and laboratories providing transfusion support has identified the heterogeneity of testing options available, areas of concern and need for improvement, and common obstacles in providing appropriate and timely support to immune-refractory PLT patients. Depending on the testing methods and the pool of HLA-typed PLT donors available, there are numerous options for developing suitable algorithms to provide effective support to immune-refractory PLT patients.

Donor-specific antibodies: can they predict C4d deposition in pediatric heart recipients?

There is limited evidence regarding the utility of circulating DSA in surveillance for AMR of pediatric heart recipients. Our hypothesis is that quantitation of DSA improves their power for predicting a C4d+, an integral component in the current diagnostic criteria of AMR. All pediatric recipients transplanted between 10/2005 and 1/2011 were retrospectively reviewed for DSA determined within 48 h of EMB. C4d+ was defined as >25% endothelial cell staining by immunohistochemical methods. A total of 183 paired DSA-EMB determinations were identified in 60 patients, a median of three paired studies per patient (range: 1-9). DSA were detected in 60 of these determinations. A receiver-operating characteristic plot identified a threshold single-antibody MFI of >6000 that strongly correlated with C4d+ (p < 0.0001) with a high negative predictive value (0.97) and specificity (0.95). The sensitivity and positive predictive values were 0.71 and 0.60, respectively. The predictive power of single-antigen DSA for C4d deposition was improved in pediatric heart recipients using an institution-specific MFI threshold value. In post-transplant care, quantitative DSA should be an essential component in the surveillance for AMR.

Apneic Technique in Laryngotracheal Surgery.

Background Apneic oxygenation can be applied to select laryngotracheal procedures to improve operative visualization and avoid potential complications associated with intubation and jet ventilation.  Aims/objectives The authors sought to determine if apneic oxygenation using a high-flow nasal cannula could be used as a safe alternative airway management strategy for the duration of select laryngotracheal procedures. Methods Single institution, multi-site retrospective review of 38 adult (>18 years old) patients undergoing apneic oxygenation in the setting of various laryngotracheal procedures from January 2017 through January 2018. Humidified oxygen was delivered via a high-flow nasal cannula. The data was collected and analyzed using SAS version 9.4 (SAS Institute, Cary, NC). Results Twenty-four women and 14 men, mean age 60.0 years (SD 16.1; 36-89) and 70.1 years (SD 7.2; 56-81), respectively, underwent a mean total apneic time of 23.9 minutes (13-40). A statistically significant correlation existed between apneic time and minimum oxygen saturation (Pearson correlation coefficient 0.38; p=0.018). Twenty-one patients resumed spontaneous ventilation without the need for jet ventilation, mask ventilation, or placement of a definitive airway during the procedure.  Conclusions and significance Apneic oxygenation allows for extended periods of operating without the need for the placement of an endotracheal tube in patients undergoing general anesthesia for select laryngotracheal procedures.

Combining donor-derived cell-free DNA and donor specific antibody testing as non-invasive biomarkers for rejection in kidney transplantation.

Donor specific anti-HLA antibodies (DSA) and donor-derived cell-free DNA (dd-cfDNA) have lead to substantial progress in the non-invasive monitoring of the renal allograft by being able to detect or rule out subclinical rejection and guide immunosuppressive changes. In this study we sought to analyze the clinical, de novo DSA (dnDSA) and histological determinants of dd-cfDNA levels. The study included a cohort of stable renal function kidney transplant (KT) recipients who underwent anti-HLA dnDSA and dd-cfDNA testing between September 2017-December 2019. Statistical models were constructed to detect association with predictors of dd-cfDNA levels and other clinical characteristics. 171 renal allograft recipients were tested for dd-cfDNA and dnDSA at a median 1.06 years posttransplant (IQR: 0.37-4.63). Median dd-cfDNA was 0.25% (IQR: 0.19-0.51), 18.7% of patients having a dd-cfDNA ≥ 1%. In a multivariate linear regression model the presence of dnDSA MFI ≥ 2500 was the best independent determinant of dd-cfDNA level (p < 0.001). Among patients tested, 54 had concurrent dd-cfDNA determination at the time of an allograft biopsy. dd-cfDNA had an AUC of 0.82 (95% CI 0.69-0.91; p < 0.001) and of 0.96 (95% CI 0.87-0.99) to discriminate any rejection and ABMR, respectively. After multivariate adjustment, the models that included ABMR (R = 0.82, R2 = 0.67, p < 0.001), or ptc (R = 0.79, R2 = 0.63, p < 0.001) showed the best correlation with dd-cfDNA level. We are confirming a strong association of dd-cfDNA with dnDSA and underlying alloimmune-mediated injury in renal allograft recipients in a cohort of patients with unsuspecting clinical characteristics for rejection and excellent allograft function. Our findings support the need for noninvasive biomarker surveillance in KT recipients and we propose that dd-cfDNA may complement dnDSA screening.

The incidence of torsades de pointes with peri-operative low-dose ondansetron administration.

STUDY OBJECTIVE: The primary objective of this retrospective safety study was to determine the incidence of torsades de pointes (TdP) or death following perioperative administration of low-dose, 4 mg, ondansetron for postoperative nausea and vomiting. DESIGN AND SETTING: This is a single-center retrospective clinical trial. PATIENTS: The authors identified 32,737 patients who received 37,589 doses of ondansetron during a 2-year time frame between March 2009 and February 2011 for surgical nausea prophylaxis or treatment of nausea. MEASUREMENTS AND MAIN RESULTS: Patients were cross-matched with an electrocardiogram and adverse outcome database; this identified 4759 patients with documentation of a QTc >450 milliseconds (ms), all ventricular tachycardias including TdP within 48 hours of receiving ondansetron, or death within 7 days of receiving ondansetron. No patients developed TdP or died as a direct result of ondansetron administration (n = 0; event rate = 0.0 per 10,000, 95% CI 0.0 to 1.1 per 10,000). Forty-six of 32,737 surgical patients had documented monomorphic ventricular tachycardia (VT) (n = 14; event rate = 4.3 per 10,000, 95% CI 2.3 to 7.2 per 10,000) or died (n = 32; event rate = 9.8 per 10,000, 95% CI 6.7 to 13.8 per 10,000) within 48 h of ondansetron administration. All monomorphic VT episodes were precipitated by existing cardiovascular disease; and 7 of 14 patients had documented monomorphic VT prior to receiving ondansetron. Of the 32 surgical patients who died, all deaths were precipitated by pre-existing disease. CONCLUSION: No episodes of TdP were identified in patients receiving ondansetron perioperatively. This suggests that low-dose ondansetron does not contribute to the development of TdP.

Donor-derived Cell-free DNA Complements De Novo Class II DSA in Detecting Late Alloimmune Injury Post Kidney Transplantation.

We sought to evaluate the association between de novo donor-specific antibodies (dnDSAs) class and their mean fluorescence intensity (MFI) with donor-derived cell-free DNA (dd-cfDNA), aiming to further clarify the biomarker utility of these noninvasive tests in relation to renal allograft function and histology. METHODS: The study included kidney transplant recipients (n = 171) who underwent surveillance testing with DSA and dd-cfDNA as part of their clinical care between September 2017 and December 2019 at our center. RESULTS: We identified dnDSA in 43 patients (25%) at a median of 4.63 y (IQR, 1.5-7) posttransplant. The presence of DSA with MFI >2500 was associated with a median dd-cfDNA of 0.96% (IQR, 0.26-2.95) significantly higher than in patients with DSA MFI <2500 (0.28%; IQR, 0.19-0.39) or without detectable DSA (0.22%; IQR, 0.17-0.37; P < 0.001). Class II dnDSAs were the most prevalent dnDSA (88.3%), the majority with MFI >2500 (82.9%). Patients with DQ-dnDSAs (47.4%) had higher MFI and dd-cfDNA levels than other class II dnDSAs. By comparison, all patients that developed only class I DSAs had MFI <2500 and a low dd-cfDNA. In addition, the serum creatinine was 1.55 ± 0.48 mg/dL in those dnDSA-negative, 1.15 ± 0.37 mg/dL in those with dnDSA MFI <2500, and 1.53 ± 0.66 mg/dL in those with dnDSA MFI >2500 (P = 0.05). After multivariate adjustment, an elevated dd-cfDNA was independently associated with the presence of dnDSA with MFI ≥2500. We identified that both dd-cfDNA and dnDSAs were strongly associated with antibody-mediated rejection, whereas for individual Banff histological lesions, DSA MFIs ≥2500 had the strongest association with C4d staining score and dd-cfDNA >1% with microvascular inflammation. CONCLUSIONS: Our study identifies class II dnDSA as being strongly associated with late alloimmune injury post kidney transplant independent of allograft dysfunction and shows that dd-cfDNA may complement the clinical significance of dnDSAs.

Targeting NKT cells and PD-L1 pathway results in augmented anti-tumor responses in a melanoma model.

Invariant or Type 1 NKT cells (iNKT cells) are a unique population of lymphocytes that share characteristics of T cells and natural killer (NK) cells. Various studies have shown that positive costimulatory pathways such as the CD28 and CD40 pathways can influence the expansion and cytokine production by iNKT cells. However, little is understood about the regulation of iNKT cells by negative costimulatory pathways. Here, we show that in vivo activation with α-GalCer results in increased cytokine production and expansion of iNKT cells in the absence of programmed cell death ligand-1 (PD-L1, B7-H1, and CD274). To study whether PD-L1 deficiency on NKT cells would enhance antigen-specific T-cell responses, we utilized CD8(+) OT-1 OVA transgenic T cells. α-GalCer enhanced the expansion and cytokine production of OT-1 CD8(+) cells after adoptive transfer into wild-type recipients. However, this expansion was significantly enhanced when OT-1 CD8(+) T cells were adoptively transferred into PD-L1(-/-) recipients. To extend these results to a tumor model, we used the B16 melanoma system. PD-L1(-/-) mice given dendritic cells loaded with antigen and α-GalCer had a significant reduction in tumor growth and this was associated with increased trafficking of antigen-presenting cells and CD8(+) T cells to the tumors. These data demonstrate that abrogating PDL1:PD-1 interactions during the activation of iNKT cells amplifies an anti-tumor response when coupled with DC vaccination.

Digoxin therapy in the elderly: pharmacokinetic considerations in nursing.

Digoxin is effective in controlling ventricular rhythm in atrial fibrillation and is used in heart failure when angiotensin converting enzyme inhibitors and diuretics are ineffective. Because use of more than 1 drug is often required with these conditions, pharmacokinetic considerations, including those related to complementary medicine, are important. Increased awareness of drug action in the elderly is important because there is often an increase in body fat and leaner muscle mass as well as changes in organ function, such as that of the kidney, which alters drug activity. Nurses have an important role to play in the safe administration of digoxin.

A Novel Approach to Emergency Airway Simulation Using a 3D-printed Cricothyrotomy Task Trainer.

BACKGROUND: Cricothyrotomy is a final recourse for salvaging a difficult airway, yet most anesthesiology providers have little training, exposure, or comfort with the procedure. Pig tracheas are frequently used for training, but are single use and require special handling and storage. Other simulation models, such as mannequins and cadavers, are costly. Advances in 3dimensional (3D) printing have improved accessibility and decreased costs. This research project sought to determine whether an inexpensive 3D-printed task trainer was noninferior to pig tracheas for teaching surgical cricothyrotomy skills. METHODS: Anesthesiology residents were enrolled in an institutional review board-exempted, unblinded, randomized, controlled, single-institution, noninferiority trial. Participants were trained in the scalpel-finger-bougie technique for surgical cricothyrotomy. Participants were randomized to practice 5 repetitions on either a pig trachea or the 3D model and were assessed on time to cricothyrotomy completion on a pig trachea before and after practice. RESULTS: Demographic characteristics of the 25 workshop attendees were similar between study arms. Overall mean (SD) improvement in speed was 9 (12) seconds (P = .001). Postpractice times were similar between groups (analysis of covariance estimated difference of -0.1 seconds [95% confidence interval, -9.4 to 9.2]; P = .55). The 3D model was noninferior to the pig trachea at the prespecified noninferiority margin of 10 seconds (P = .017). CONCLUSIONS: The 3D model was noninferior to pig tracheas for improving the time to completion of a surgical cricothyrotomy. A 3D-printed model offers a viable alternative to pig tracheas for emergency airway simulation that is inexpensive, reusable, and readily modified to simulate challenging airway anatomy.

Impaired graft survival in pediatric renal transplant recipients with donor-specific antibodies detected by solid-phase assays.

SAB assays have increased the sensitivity and specificity to detect HLA alloantibodies, but there is uncertainty about the clinical relevance of SAB-positive alloantibodies when the FCXM is negative. We performed a retrospective study to evaluate the clinical significance of SAB-detected DSA in 82 pediatric recipients of a first kidney transplant between January 2000 and December 2005 who had a negative pretransplant FCXM. Pretransplant sera were evaluated by SAB for DSA. Graft loss and rejection between patients with (DSA+) and without DSA (DSA-) were compared. DSA were detected in 13.9%. Eighty percent of DSA+ subjects were DD transplant recipients vs. 56.9% in the DSA- cohort. The RR of graft loss in DSA+ vs. DSA- was 3.3 (95% CI, 1.4-7.9) and in DD was 4.3 (95% CI 1.4-13.1). By Cox regression, the HR of graft loss in DSA+ vs. DSA- was 2.8 (95% CI 0.7-10.9; p = 0.14) and in DD was 5.1 (95% CI 1-25.6; p = 0.05). Acute rejection occurred in 60% in the DSA+ vs. 44.4% in DSA- (p = 0.5). SAB-detected DSA was associated with impaired renal allograft survival in pediatric renal transplant recipients. Impaired graft survival in pediatric renal transplant recipients with DSA detected by solid-phase assays.