The complex relationship between pediatric cardiac surgical case volumes and mortality rates in a national clinical database

ObjectiveWe sought to determine the association between pediatric cardiac surgical volume and mortality using sophisticated case-mix adjustment and a national clinical database.MethodsPatients 18 years of age or less who had a cardiac operation between 2002 and 2006 were identified in the Society of Thoracic Surgeons Congenital Heart Surgery Database (32,413 patients from 48 programs). Programs were grouped by yearly pediatric cardiac surgical volume (small, <150; medium, 150–249; large, 250–349; and very large, ≥350 cases per year). Logistic regression was used to adjust mortality rates for volume, surgical case mix (Aristotle Basic Complexity and Risk Adjustment for Congenital Heart Surgery, Version 1 categories), patient risk factors, and year of operation.ResultsWith adjustment for patient-level risk factors and surgical case mix, there was an inverse relationship between overall surgical volume as a continuous variable and mortality (P = .002). When the data were displayed graphically, there appeared to be an inflection point between 200 and 300 cases per year. When volume was analyzed as a categorical variable, the relationship was most apparent for difficult operations (Aristotle technical difficulty component score, >3.0), for which mortality decreased from 14.8% (60/406) at small programs to 8.4% (157/1858) at very large programs (P = .02). The same was true for the subgroup of patients who underwent Norwood procedures (36.5% [23/63] vs 16.9% [81/479], P < .0001). After risk adjustment, all groups performed similarly for low-difficulty operations. Conversely, for difficult procedures, small programs performed significantly worse. For Norwood procedures, very large programs outperformed all other groups.ConclusionThere was an inverse association between pediatric cardiac surgical volume and mortality that became increasingly important as case complexity increased. Although volume was not associated with mortality for low-complexity cases, lower-volume programs underperformed larger programs as case complexity increased

Human Innate Mycobacterium tuberculosis–Reactive αβTCR+ Thymocytes

The control of Mycobacterium tuberculosis (Mtb) infection is heavily dependent on the adaptive Th1 cellular immune response. Paradoxically, optimal priming of the Th1 response requires activation of priming dendritic cells with Th1 cytokine IFN-γ. At present, the innate cellular mechanisms required for the generation of an optimal Th1 T cell response remain poorly characterized. We hypothesized that innate Mtb-reactive T cells provide an early source of IFN-γ to fully activate Mtb-exposed dendritic cells. Here, we report the identification of a novel population of Mtb-reactive CD4− αβTCR+ innate thymocytes. These cells are present at high frequencies, respond to Mtb-infected cells by producing IFN-γ directly ex vivo, and display characteristics of effector memory T cells. This novel innate population of Mtb-reactive T cells will drive further investigation into the role of these cells in the containment of Mtb following infectious exposure. Furthermore, this is the first demonstration of a human innate pathogen-specific αβTCR+ T cell and is likely to inspire further investigation into innate T cells recognizing other important human pathogens

Inhaled nitric oxide, right ventricular efficiency, and pulmonary vascular mechanics: Selective vasodilation of small pulmonary vessels during hypoxic pulmonary vasoconstriction

AbstractObjective: In the setting of acute pulmonary artery hypertension, techniques to reduce right ventricular energy requirements may ameliorate cardiac failure and reduce morbidity and mortality. Inhaled nitric oxide, a selective pulmonary vasodilator, may be effective in the treatment of pulmonary artery hypertension, but its effects on cardiopulmonary interactions are poorly understood. Methods: We therefore developed a model of hypoxic pulmonary vasoconstriction that mimics the clinical syndrome of acute pulmonary hypertension. Inhaled nitric oxide was administered in concentrations of 20, 40, and 80 ppm. Results: During hypoxic pulmonary vasoconstriction, the administration of nitric oxide resulted in a significant improvement in pulmonary vascular mechanics and a reduction in right ventricular afterload. These improvements were a result of selective vasodilation of small pulmonary vessels and more efficient blood flow through the pulmonary vascular bed (improved transpulmonary vascular efficiency). The right ventricular total power output diminished during the inhalation of nitric oxide, indicating a reduction in right ventricular energy requirements. The net result of nitric oxide administration was an increase in right ventricular efficiency. Conclusion: These data suggest that nitric oxide may be beneficial to the failing right ventricle by improving pulmonary vascular mechanics and right ventricular efficiency. (J Thorac Cardiovasc Surg 1997;113:1006-13

Modified ultrafiltration improves cerebral metabolic recovery after circulatory arrest

AbstractModified ultrafiltration uses hemofiltration of the patient and bypass circuit after separation from cardiopulmonary bypass to reverse hemodilution and edema. This study investigated the effect of modified ultrafiltration on cerebral metabolic recovery after deep hypothermic circulatory arrest. Twenty-six 1-week-old piglets (2 to 3 kg) were supported by cardiopulmonary bypass (37° C) at 100 ml · kg-1 · min-1 and cooled to 18° C. Animals underwent 90 minutes of circulatory arrest followed by rewarming to 37° C. After being weaned from cardiopulmonary bypass, animals were divided into three groups: controls ( n = 10); modified ultrafiltration for 20 minutes ( n = 9); transfusion of hemoconcentrated blood for 20 minutes ( n = 7). Global cerebral blood flow was measured by xenon 133 clearance methods: stage I--before cardiopulmonary bypass; stage II—5 minutes after cardiopulmonary bypass; and stage III—25 minutes after cardiopulmonary bypass. Cerebral metabolic rate of oxygen consumption, cerebral oxygen delivery, and hematocrit value were calculated for each time point. At point III, the hematocrit value (percent) was elevated above baseline in the ultrafiltration and transfusion groups (44 ± 1.8, 42 ± 1.8 versus 28 ± 1.7, 30 ± 0.7, respectively, p < 0.05). Cerebral oxygen delivery (ml · 100 gm-1 · min-1 ) increased significantly above baseline at point III after ultrafiltration (4.98 ± 0.32 versus 3.85 ± 0.16, p < 0.05) or transfusion (4.59 ± 0.17 versus 3.89 ± 0.06, p < 0.05) and decreased below baseline in the control group (2.77 ± 0.19 versus 3.81 ± 0.16, p < 0.05). Ninety minutes of deep hypothermic circulatory arrest resulted in impaired cerebral metabolic oxygen consumption (ml · 100 gm-1 · min-1 ) at point III in the control group (1.95 ± 0.15 versus 2.47 ± 0.07, p < 0.05) and transfusion group (1.72 ± 0.10 versus 2.39 ± 0.15, p < 0.05). After modified ultrafiltration, however, cerebral metabolic oxygen consumption at point III had increased significantly from baseline (3.12 ± 0.24 versus 2.48 ± 0.13, p < 0.05), indicating that the decrease in cerebral metabolism immediately after deep hypothermic circulatory arrest is reversible and may not represent permanent cerebral injury. Use of modified ultrafiltration after cardiopulmonary bypass may reduce brain injury associated with deep hypothermic circulatory arrest. (J THORAC CARDIOVASC SURG 1995;109:744-52

Impact of Visual Repetition Rate on Intrinsic Properties of Low Frequency Fluctuations in the Visual Network

BACKGROUND: Visual processing network is one of the functional networks which have been reliably identified to consistently exist in human resting brains. In our work, we focused on this network and investigated the intrinsic properties of low frequency (0.01-0.08 Hz) fluctuations (LFFs) during changes of visual stimuli. There were two main questions to be discussed in this study: intrinsic properties of LFFs regarding (1) interactions between visual stimuli and resting-state; (2) impact of repetition rate of visual stimuli. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed scanning sessions that contained rest and visual stimuli in various repetition rates with a novel method. The method included three numerical approaches involving ICA (Independent Component Analyses), fALFF (fractional Amplitude of Low Frequency Fluctuation), and Coherence, to respectively investigate the modulations of visual network pattern, low frequency fluctuation power, and interregional functional connectivity during changes of visual stimuli. We discovered when resting-state was replaced by visual stimuli, more areas were involved in visual processing, and both stronger low frequency fluctuations and higher interregional functional connectivity occurred in visual network. With changes of visual repetition rate, the number of areas which were involved in visual processing, low frequency fluctuation power, and interregional functional connectivity in this network were also modulated. CONCLUSIONS/SIGNIFICANCE: To combine the results of prior literatures and our discoveries, intrinsic properties of LFFs in visual network are altered not only by modulations of endogenous factors (eye-open or eye-closed condition; alcohol administration) and disordered behaviors (early blind), but also exogenous sensory stimuli (visual stimuli with various repetition rates). It demonstrates that the intrinsic properties of LFFs are valuable to represent physiological states of human brains

The what and why of perceptual asymmetries in the visual domain

Perceptual asymmetry is one of the most important characteristics of our visual functioning. We carefully reviewed the scientific literature in order to examine such asymmetries, separating them into two major categories: within-visual field asymmetries and between-visual field asymmetries. We explain these asymmetries in terms of perceptual aspects or tasks, the what of the asymmetries; and in terms of underlying mechanisms, the why of the asymmetries. Tthe within-visual field asymmetries are fundamental to orientation, motion direction, and spatial frequency processing. between-visual field asymmetries have been reported for a wide range of perceptual phenomena. foveal dominance over the periphery, in particular, has been prominent for visual acuity, contrast sensitivity, and colour discrimination. Tthis also holds true for object or face recognition and reading performance. upper-lower visual field asymmetries in favour of the lower have been demonstrated for temporal and contrast sensitivities, visual acuity, spatial resolution, orientation, hue and motion processing. Iin contrast, the upper field advantages have been seen in visual search, apparent size, and object recognition tasks. left-right visual field asymmetries include the left field dominance in spatial (e.g., orientation) processing and the right field dominance in non-spatial (e.g., temporal) processing. left field is also better at low spatial frequency or global and coordinate spatial processing, whereas the right field is better at high spatial frequency or local and categorical spatial processing. All these asymmetries have inborn neural/physiological origins, the primary why, but can be also susceptible to visual experience, the critical why (promotes or blocks the asymmetries by altering neural functions)

Best practice for motor imagery: a systematic literature review on motor imagery training elements in five different disciplines

<p>Abstract</p> <p>Background</p> <p>The literature suggests a beneficial effect of motor imagery (MI) if combined with physical practice, but detailed descriptions of MI training session (MITS) elements and temporal parameters are lacking. The aim of this review was to identify the characteristics of a successful MITS and compare these for different disciplines, MI session types, task focus, age, gender and MI modification during intervention.</p> <p>Methods</p> <p>An extended systematic literature search using 24 databases was performed for five disciplines: Education, Medicine, Music, Psychology and Sports. References that described an MI intervention that focused on motor skills, performance or strength improvement were included. Information describing 17 MITS elements was extracted based on the PETTLEP (physical, environment, timing, task, learning, emotion, perspective) approach. Seven elements describing the MITS temporal parameters were calculated: study duration, intervention duration, MITS duration, total MITS count, MITS per week, MI trials per MITS and total MI training time.</p> <p>Results</p> <p>Both independent reviewers found 96% congruity, which was tested on a random sample of 20% of all references. After selection, 133 studies reporting 141 MI interventions were included. The locations of the MITS and position of the participants during MI were task-specific. Participants received acoustic detailed MI instructions, which were mostly standardised and live. During MI practice, participants kept their eyes closed. MI training was performed from an internal perspective with a kinaesthetic mode. Changes in MI content, duration and dosage were reported in 31 MI interventions. Familiarisation sessions before the start of the MI intervention were mentioned in 17 reports. MI interventions focused with decreasing relevance on motor-, cognitive- and strength-focused tasks. Average study intervention lasted 34 days, with participants practicing MI on average three times per week for 17 minutes, with 34 MI trials. Average total MI time was 178 minutes including 13 MITS. Reporting rate varied between 25.5% and 95.5%.</p> <p>Conclusions</p> <p>MITS elements of successful interventions were individual, supervised and non-directed sessions, added after physical practice. Successful design characteristics were dominant in the Psychology literature, in interventions focusing on motor and strength-related tasks, in interventions with participants aged 20 to 29 years old, and in MI interventions including participants of both genders. Systematic searching of the MI literature was constrained by the lack of a defined MeSH term.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival