Cytokines are signaling molecules secreted and sensed by immune and other cell types, enabling dynamic intercellular communication. Although a vast amount of data on these interactions exists, this information is not compiled, integrated or easily searchable. Here we report immuneXpresso, a text-mining engine that structures and standardizes knowledge of immune intercellular communication. We applied immuneXpresso to PubMed to identify relationships between 340 cell types and 140 cytokines across thousands of diseases. The method is able to distinguish between incoming and outgoing interactions, and it includes the effect of the interaction and the cellular function involved. These factors are assigned a confidence score and linked to the disease. By leveraging the breadth of this network, we predicted and experimentally verified previously unappreciated cell-cytokine interactions. We also built a global immune-centric view of diseases and used it to predict cytokine-disease associations. This standardized knowledgebase (http://www.immunexpresso.org) opens up new directions for interpretation of immune data and model-driven systems immunology.

Background Privacy restrictions limit access to protected patient-derived health information for research purposes. Consequently, data anonymization is required to allow researchers data access for initial analysis before granting institutional review board approval. A system installed and activated at our institution enables synthetic data generation that mimics data from real electronic medical records, wherein only fictitious patients are listed. Objective This paper aimed to validate the results obtained when analyzing synthetic structured data for medical research. A comprehensive validation process concerning meaningful clinical questions and various types of data was conducted to assess the accuracy and precision of statistical estimates derived from synthetic patient data. Methods A cross-hospital project was conducted to validate results obtained from synthetic data produced for five contemporary studies on various topics. For each study, results derived from synthetic data were compared with those based on real data. In addition, repeatedly generated synthetic datasets were used to estimate the bias and stability of results obtained from synthetic data. Results This study demonstrated that results derived from synthetic data were predictive of results from real data. When the number of patients was large relative to the number of variables used, highly accurate and strongly consistent results were observed between synthetic and real data. For studies based on smaller populations that accounted for confounders and modifiers by multivariate models, predictions were of moderate accuracy, yet clear trends were correctly observed. Conclusions The use of synthetic structured data provides a close estimate to real data results and is thus a powerful tool in shaping research hypotheses and accessing estimated analyses, without risking patient privacy. Synthetic data enable broad access to data (eg, for out-of-organization researchers), and rapid, safe, and repeatable analysis of data in hospitals or other health organizations where patient privacy is a primary value.

This study characterizes, for the first time, contacts to CdZnTe radiation detectors by measuring the dark noise spectra as a function of the applied bias. The noise currents are correlated with the dc dark current-voltage characteristics of CdZnTe x-ray and gamma-ray detectors. In order to identify and separate the role of the contacts in the overall performance, the measured noise phenomena is correlated with detector configuration and contact design as well as the growth method of the CdZnTe crystals, contact technology, and passivation. Several contact technologies (electroless gold, and a number of evaporated metallic contacts including gold, indium, zinc, titanium, aluminum, and platinum contacts) are compared. Contacts to CdZnTe crystals grown by high pressure Bridgman are compared with contacts to CdZnTe crystals grown by modified Bridgman. Contacts of resistive detectors as well as of Schottky detectors are reported. Large area symmetric contacts are compared with small area pixelized contacts. The role of the metallization used for contacts, the role of surface effects and passivation, and the role of contact design are discussed.

Background The overall risk of postcontrast acute kidney injury (PC-AKI) after computerized tomography (CT) is negligible, likely because of the small volume of injected iodinated contrast media required. However, the safety of contrast media–enhanced CT in patients with advanced renal functional impairment, an established major risk factor for PC-AKI, is unknown. Materials and Methods This is a retrospective study using large data analysis of hospitalized patients at a single center. Adults undergoing CT or magnetic resonance imaging were included in the study and were stratified by estimated glomerular filtration rate (eGFR) (≤30 or >30 mL/min/1.73 m2) and by either contrast-enhanced or nonenhanced imaging. Only patients with serial determination of creatinine before and after imaging were included. Demographic, clinical, and laboratory data between groups were analyzed and compared using univariate analysis, propensity score matching, and multivariate logistic regression analysis. Results A total of 22,319 imaging studies were included. Patients with an eGFR of 30 mL/min/1.73 m2 or lower undergoing contrast-enhanced CT (n = 403) had an increased risk to develop PC-AKI than did similar patients undergoing enhanced or nonenhanced magnetic resonance imaging (n = 96) or nonenhanced CT (n = 1576) or patients undergoing contrast-enhanced CT with a preprocedural eGFR higher than 30 mL/min/1.73 m2 (n = 9173). These findings remained robust after propensity matching for demographic, procedural, and clinical parameters. Multivariate regression analysis of all patients undergoing CT with preimaging eGFR of 30 mL/min or lower (n = 1979) revealed that iodine-based contrast enhancement increased the likelihood of post-CT AKI by 51% (confidence interval, 1.23–2.05). Conclusion Although radiocontrast-enhanced CT is considered safe in most hospitalized patients and in ambulatory settings, the risk of PC-AKI remains significant among inpatients with substantial preimaging renal functional impairment. Caution is warranted using iodine-based enhanced CT in hospitalized patients with an eGFR of 30 mL/min/1.73 m2 or lower.

IntroductionAcute kidney injury associated with near-drowning (ND-AKI) has rarely been reported and its incidence among survivors is unknown. A patient with AKI and urine biomarkers indicating tubular injury led us to assess the occurrence and clinical characteristics of ND-AKI and to evaluate possible causative mechanisms.MethodsWe evaluated medical records of patients rescued from near-drowning in the Mediterranean Sea and treated in a tertiary-level medical center during 2000 to 2017.ResultsNinety-five patients with the diagnosis of near-drowning in seawater were treated. Forty-two of these patients (43%) developed ND-AKI and 17 (18%) were classified as AKI Kidney Disease: Improving Global Outcomes stages 2 to 3. ND-AKI was associated with the need for resuscitation and mechanical ventilation, with the calculated seawater volume ingestion (extrapolated from rising plasma sodium) and with the degree of acidemia, lactemia, and ventilatory failure. This series and 28 additional published cases of ND-AKI in the literature showed an overall male predisposition.ConclusionAKI is a common complication of near-drowning and is associated with increased in-hospital mortality. Data analysis suggests a predominant role of hypoxic tubular injury due to systemic hypoxemia in ND-AKI, combined with intense sympathetic activity (reflected by tachyarrhythmias, hyperglycemia, and relative hypokalemia) and increased oxygen expenditure for intensified distal tubular sodium transport. Androgen-related reduced renal vasodilatory capacity may explain male gender predominance.

ObjectiveAnti-drug antibodies (ADA) to anti-tumour necrosis factor (anti-TNF) therapy drive treatment loss of response. An association between intestinal microbial composition and response to anti-TNF therapy was noted. We therefore aimed to assess the implications of antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD).DesignWe analysed data from the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all patients with IBD in Israel. We included all patients treated with anti-TNF who had available ADA levels. Survival analysis with drug use as time varying covariates were used to assess the association between antibiotic use and ADA development. Next, specific pathogen and germ-free C57BL mice were treated with respective antibiotics and challenged with infliximab. ADA were assessed after 14 days.ResultsAmong 1946 eligible patients, with a median follow-up of 651 days from initiation of therapy, 363 had positive ADA. Cox proportional hazard model demonstrated an increased risk of ADA development in patients who used cephalosporins (HR=1.97, 95% CI 1.58 to 2.44), or penicillins with β-lactamase inhibitors (penicillin-BLI, HR=1.4, 95% CI 1.13 to 1.74), whereas a reduced risk was noted in patients treated with macrolides (HR=0.38, 95% CI 0.16 to 0.86) or fluoroquinolones (HR=0.20, 95% CI 0.12 to 0.35). In mice exposed to infliximab, significantly increased ADA production was observed in cephalosporin as compared with macrolide pretreated mice. Germ-free mice produced no ADA.ConclusionADA production is associated with the microbial composition. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillin-BLIs, or by treatment with fluoroquinolones or macrolides.

Background: Large data analyses confirm the relative safety of contrast-enhanced computed tomography (CT), except for those with advanced renal failure. However, the prevalence of post-contrast acute kidney injury may be masked by acute kidney functional recovery (AKR) in unstable inpatients, irrespective of contrast-enhanced imaging. Methods: In this work we aimed to assess AKI and AKR along with need for dialysis and mortality, among inpatients undergoing contrast-enhanced or non-enhanced CT. We performed a large-scale retrospective data analysis using propensity score matching (PSM) that compared patients undergoing contrast-enhanced and non-enhanced imaging. We also performed a subgroup analysis of subjects stratified by baseline renal function. Results: A total of 41,456 patients were analyzed. PSM resulted in well-balanced groups. AKR occurred substantially more often than AKI among hospitalized patients following CT imaging, especially among those with low baseline renal function. Yet, in this population, whereas the rate of AKI significantly increased, the rate of AKR significantly decreased following contrast-enhanced studies as compared to patients that underwent non-enhanced CT. A significantly higher proportion of patients with baseline advanced renal failure that underwent contrast-enhanced imaging required dialysis. Conclusions: The increased incidence of AKI and AKR as seen in patients with lower pre-imaging kidney function possibly suggests that both entities reflect impaired renal functional reserve. Unstable kidney function in inpatients, as demonstrated by rates of AKR and AKI, is an important confounder which requires attention in similar observational studies on the renal effects of contrast media and of various other renal injurious events.

No abstract