Ata Murat Kaynar

Intensivist-Led Management of Brain-Dead Donors Is Associated with an Increase in Organ Recovery for Transplantation

The disparity between the number of patients in need of organ transplantation and the number of available organs is steadily rising. We hypothesized that intensivist‐led management of brain dead donors would increase the number of organs recovered for transplantation. We retrospectively analyzed data from all consented adult brain dead patients in the year before (n = 35) and after (n = 43) implementation of an intensivist‐led donor management program. Donor characteristics before and after implementation were similar. After implementation of the organ donor support team, the overall number of organs recovered for transplantation increased significantly (66 out of 210 potentially available organs vs. 113 out of 258 potentially available organs, p = 0.008). This was largely due to an increase in the number of lungs (8 out of 70 potentially available lungs vs. 21 out of 86 potentially available lungs; p = 0.039) and kidneys (31 out of 70 potentially available kidneys vs. 52 out of 86 potentially available kidneys; p = 0.044) recovered for transplantation. The number of hearts and livers recovered for transplantation did not change significantly. Institution of an intensivist‐led organ donor support team may be a new and viable strategy to increase the number of organs available for transplantations.

Effects of intra-abdominal sepsis on atherosclerosis in mice.

IntroductionSepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis.MethodsWe performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE−/−) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE−/− mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation.ResultsApoE−/− mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2 and vascular cell adhesion molecule 1) and the adhesion assay, a functional measure of endothelial activation, were elevated at 72 hours and 120 hours in mice that underwent CLP versus sham-operations (all at P <0.05).ConclusionsUsing a combination of existing murine models for atherosclerosis and sepsis, we found that CLP, a model of intra-abdominal sepsis, accelerates atheroma development. Accelerated atheroma burden was associated with prolonged systemic, endothelial and intimal inflammation and was not explained by ongoing infection. These findings support observations in humans and demonstrate the feasibility of a long-term follow-up murine model of sepsis.

Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study

INTRODUCTION Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We designed an extracorporeal hemoadsorption device capable of capturing both cytokines and leukocytes in order to test the hypothesis that leukocyte capture would alter circulating cytokine profiles and influence immunological cell-cell interactions in whole blood taken from patients with sepsis. METHODS We performed a series of ex vivo studies in 21 patients with septic shock and 12 healthy volunteers. Blood circulated for four hours in closed loops with four specially designed miniaturized extracorporeal blood purification devices including two different hemoadsorption devices and a hemofilter in order to characterize leukocyte capture and to assess the effects of leukocyte removal on inflammation and immune function. RESULTS Hemoadsorption was selective for removal of activated neutrophils and monocytes. Capture of these cells led to local release of certain cytokines, especially IL-8, and resulted in complex cell-cell interactions involved in cell-mediated immunity. Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function. CONCLUSIONS Monocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity. Further studies are needed to understand better these cellular interactions in order to help design better blood purification therapies.

Using Supervised Machine Learning to Classify Real Alerts and Artifact in Online Multisignal Vital Sign Monitoring Data.

Objective: The use of machine-learning algorithms to classify alerts as real or artifacts in online noninvasive vital sign data streams to reduce alarm fatigue and missed true instability. Design: Observational cohort study. Setting: Twenty-four–bed trauma step-down unit. Patients: Two thousand one hundred fifty-three patients. Intervention: Noninvasive vital sign monitoring data (heart rate, respiratory rate, peripheral oximetry) recorded on all admissions at 1/20 Hz, and noninvasive blood pressure less frequently, and partitioned data into training/validation (294 admissions; 22,980 monitoring hours) and test sets (2,057 admissions; 156,177 monitoring hours). Alerts were vital sign deviations beyond stability thresholds. A four-member expert committee annotated a subset of alerts (576 in training/validation set, 397 in test set) as real or artifact selected by active learning, upon which we trained machine-learning algorithms. The best model was evaluated on test set alerts to enact online alert classification over time. Measurements and Main Results: The Random Forest model discriminated between real and artifact as the alerts evolved online in the test set with area under the curve performance of 0.79 (95% CI, 0.67–0.93) for peripheral oximetry at the instant the vital sign first crossed threshold and increased to 0.87 (95% CI, 0.71–0.95) at 3 minutes into the alerting period. Blood pressure area under the curve started at 0.77 (95% CI, 0.64–0.95) and increased to 0.87 (95% CI, 0.71–0.98), whereas respiratory rate area under the curve started at 0.85 (95% CI, 0.77–0.95) and increased to 0.97 (95% CI, 0.94–1.00). Heart rate alerts were too few for model development. Conclusions: Machine-learning models can discern clinically relevant peripheral oximetry, blood pressure, and respiratory rate alerts from artifacts in an online monitoring dataset (area under the curve > 0.87).

A trial of intracranial pressure monitoring in traumatic brain injury

BACKGROUND Intracranial pressure (ICP) monitoring is considered the standard of care for severe traumatic brain injury (TBI) and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed. METHODS OBJECTIVE The objective was to compare efficacy of guideline-based management in which a protocol for monitoring intraparenchymal ICP was used (ICP group) or a protocol in which treatment was based on imaging and clinical examination (exam group). DESIGN A multicenter randomized controlled trial was conducted. SETTING The trial was set in ICUs in Bolivia or Ecuador. SUBJECTS Patients had severe TBI (n = 324) and were 13 years of age or older. INTERVENTIONS Patients were randomly allocated to ICP monitoring or clinical exam-based monitoring. OUTCOMES The primary outcome was a composite of survival time, impaired consciousness, functional status at 3 and 6 months, and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of the protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and was calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance). RESULTS There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score 56 in the pressure-monitoring group versus 53 in the imaging-clinical examination group; P = 0.49). Six-month mortality rates were 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P = 0.60). The median lengths of stay in the ICU were similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging-clinical examination group; P = 0.25), although the number of days of brain-specific treatments (for example, administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 versus 3.4, P = 0.002). The distributions of serious adverse events were similar in the two groups. CONCLUSIONS For patients with severe TBI, care focused on maintaining monitored ICP at 20 mmHg or less was not shown to be superior to care based on imaging and clinical examination.

Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate.

Electronic cigarettes: the lesser of two evils, but how much less?

No legal habit has caused more morbidity and mortality than cigarette smoking which takes greater than 10 years away from the average smokers life, being a major risk factor for the leading causes of mortality in both developed and low-income/middle-income countries, including coronary artery disease, cancers (especially lung cancer) and COPD.1–4 While cigarette smoking is increasing worldwide, we have made slow but steady progress in the USA reducing smoking prevalence to 18% of adults. Nicotine replacement therapy has assisted many smokers to quit; however, with the advent of electronic cigarettes (e-cigarettes), investigators began to wonder to what extent vaporised nicotine is responsible for disease pathogenesis beyond its addictive properties. Nicotine modulates inflammation causing both inflammatory cell apoptosis5 and inflammatory cell chemotaxis.6 There is growing evidence that e-cigarettes increase the risk for oxidative burden and inflammation in the lungs of mice.7 The study by Garcia-Arcos et al 8 published in Thorax convincingly demonstrates that chronic exposure (4 months) of inhaled e-cigarettes in mice causes characteristic changes observed in COPD, including airway pathology, inflammation and emphysematous lung destruction. Are preclinical models of COPD sufficient to consider regulating the use of e-cigarettes? Murine models of disease are often criticised for lack of …

Are plasma mineral levels related to antibody response to influenza vaccination in older adults

abstract Introduction: An effective immune response to vaccination may be related to nutritional status. This study examined the association of plasma mineral levels with hemagglutination inhibition (HI) titers produced in response to influenza vaccine in older adults. Methods: Prior to (Day 0) and 21 (range = 19–28) days after receiving the 2013–14 influenza vaccine, 109 adults ages 51–81 years, provided blood samples. Serum samples were tested for HI activity against the A/H1N1 and A/H3N2 2013–2014 vaccine virus strains. Plasma minerals were collected in zinc-free tubes and assayed by inductively coupled plasma mass spectrometry. HI titers were reported as seroprotection (≥1:40) and seroconversion (≥ 4-fold rise from Day 0 (minimum HI = 1:10) to Day 21). Both HI titers and mineral values were skewed and thus log2 transformed. Magnesium (Mg), phosphorus (P), zinc (Zn), copper (Cu), iron (Fe), potassium (K) and the Cu to Zn ratio were tested. Logistic regression analyses were used to determine the associations between mineral levels and seroconversion and seroprotection of HI titers for each influenza A strain. Results: Participants were 61% white, 28% male, 39% diabetic, and 81% overweight/obese with a mean age of 62.6 y. In logistic regression, Day 21 A/H1N1 seroprotection was associated with P and Zn at Day 21(P < 0.05). Seroconversion of A/H1N1 was associated with Day 21 Cu, P, and Mg (P < 0.03). Day 21 A/H3N2 seroprotection and seroconversion were associated with Day 21 P (P < 0.05). Conclusions: Phosphorus was associated with seroprotection and seroconversion to influenza A after vaccination; these associations warrant additional studies with larger, more diverse population groups.

Machine learning can classify vital sign alerts as real or artifact in online continuous monitoring data

Alarm hazards continue to be the top patient safety concern of 2015. Machine learning (ML) can be used to classify patterns in monitoring data to differentiate real alerts from artifact.