25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Successful Treatment with Crizotinib in Mechanically Ventilated Patients with ALK Positive Non–Small-Cell Lung Cancer

Lung cancer is the most common solid tumor in critically ill cancer patients admitted to intensive care units and is associated with a poor prognosis. Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor, which is active for advanced non–small cell lung cancer (NSCLC) patients harboring ALK rearrangements. We report three cases of NSCLC patients who required mechanical ventilation for respiratory failure and were successfully weaned from mechanical ventilation after treatment with ALK inhibitors. These responses were accompanied by minimal toxicities and an overt improvement in performance status. These results suggest that ALK inhibitors may be safe and effective in critically ill patients on mechanical ventilation for respiratory failure resulting from EML4-ALK translocated NSCLC progression

Inverted Ion Current Rectification-Based Chemical Delivery Probes for Stimulation of Neurons

Ion current rectification (ICR), diodelike behavior in surface-charged nanopores, shows promise in the design of delivery probes for manipulation of neural networks as it can solve diffusive leakages that might be critical in clinical and research applications. However, it has not been achieved because ICR has restrictions in nanosized dimension and low electrolyte concentration, and rectification direction is inappropriate for delivery. Herein, we present a polyelectrolyte gel-filled (PGF) micropipette harnessing inverted ICR as a delivery probe, which quantitatively transports glutamate to stimulate primary cultured neurons with high efficiency while minimizing leakages. Since the gel works as an ensemble of numerous surface-charged nanopores, the current is rectified in the micro-opening and physiological environment. By extending the charge-selective region using the gel, inverted ICR is generated, which drives outward deliveries of major charge carriers. This study will help in exploring new aspects of ICR and broaden its applications for advanced chemical delivery.11Nsciescopu

Clonal expansion of resident memory T cells in peripheral blood of patients with non-small cell lung cancer during immune checkpoint inhibitor treatment

Background Immune checkpoint inhibitors (ICIs) are an essential treatment for non-small cell lung cancer (NSCLC). Currently, the tumor-related intrinsic factors in response to ICIs have mostly been elucidated in tissue samples. However, tissue immune status and changes in the immune microenvironment can also be reflected and monitored through peripheral blood.Methods Single-cell RNA and T cell receptor (scTCR) sequencing were conducted using peripheral blood mononuclear cells (PBMCs) from 60 patients with stage IV NSCLC. Those samples were prospectively acquired from patients treated with anti-PD(L)-1 therapy for advanced lung cancer. Based on the clinical outcomes, samples were classified as durable clinical benefit (DCB) and non-durable clinical benefit (NCB). The samples constituted paired longitudinal samples, consisting of pre-treatment and on-treatment. Additionally, PBMC samples from 60 healthy donors from the Asian Immune Diversity Atlas project were used as a control.Results The dynamic changes in major cell types between pre-treatment and on-treatment PBMCs were associated with an increase in proliferating T cells and NK cells in both DCB and NCB groups. Among T cell subtypes, effector memory CD8+ T cells (CD8+ TEM_GZMK_PDCD1) were increased after ICI treatment in both DCB and NCB. From the lineage trajectory analysis, effector memory CD8+ T cells resided at the bifurcation point, which has the potential to differentiate into lineages with precursor exhausted CD8+ T cells (CD8+ TCM cells) assumed to be related to the ICI response. From the scTCR-seq, effector memory CD8+ T cells along with T cells recognizing unknown antigen expanded and composed of novel clones skewed toward dysfunctional status, especially in on-treatment samples of the DCB group. The extent of immunophenotype conversion capabilities of the TCR with effector memory CD8+ T cells showed remarkable variation in the on-treatment sample in the DCB group.Conclusion A transitioning T cell subtype identified in PBMCs might be related to the prolonged ICI response. From our study, expansion of effector memory CD8+ T cells with novel TCRs in PBMCs after ICI treatment could contribute to a better clinical outcome in patients with NSCLC. This proof-of-concept research strengthens the use of non-invasive PBMCs in studying systemic changes of immune reactions related to the ICI treatment

Role of ¹⁸F-FDG PET/CT in patients without known primary malignancy with skeletal lesions suspicious for cancer metastasis

<div><p>Background</p><p>When subjects without a known malignancy present with suspicious skeletal lesions, differential diagnosis and primary cancer identification is important. Here, we investigated the role of FDG PET/CT in this clinical situation.</p><p>Methods</p><p>We enrolled 103 patients with no known malignancies who were referred for FDG PET/CT because of bone lesions that were suspicious for cancer metastasis. Each extra-skeletal FDG lesion was categorized as consistent with primary cancer or with metastasis based on the distribution and pattern of all abnormal lesions in the individual.</p><p>Results</p><p>Final diagnosis revealed that bone lesions represented cancer metastasis in 75 patients (72.8%). In the remaining 28 patients (27.2%), they were from other causes including multiple myeloma or lymphoma, malignant primary bone tumor, and benign bone disease. PET/CT indicated a primary cancer in 70 patients (68.0%). This was the correct primary site in 46 cases and the incorrect site in 13 cases (including 6 cases with cancer of unknown primary, CUP). In the remaining 11 cases, the bone lesions were due to other causes. PET/CT did not indicate a primary cancer in 33 patients (32.0%). Of these cases, 17 did not have a primary cancer, 8 had CUP, and 8 had primary cancers that were missed. Thus, PET/CT had a sensitivity of 61.3% and specificity of 60.7% for primary cancer identification in the entire population. Excluding patients with CUP, PET/CT sensitivity was 75.4%. PET/CT also provided information useful for recognizing multiple myeloma and benign bone disease as the cause of the skeletal lesions.</p><p>Conclusions</p><p>In patients without known malignancies with suspected skeletal cancer metastasis, FDG PET/CT can help identify the primary cancer and provide useful information for differential diagnosis.</p></div