Effects of albumin and Ringer's lactate on production of lung cytokines and hydrogen peroxide after resuscitated hemorrhage and endotoxemia in rats

RATIONALE AND HYPOTHESIS: Acute lung injury is a frequent complication of severe sepsis or blood loss and is often associated with an excessive inflammatory response requiring mechanical ventilation. We tested the hypothesis that the types of fluids used during early resuscitation have an important effect on the evolution of lung injury. METHODS: Rats were subjected to either hemorrhage or endotoxemia for 1 hr, followed by resuscitation to a controlled mean blood pressure with Ringer's lactate, 5% albumin, or 25% albumin for 1 hr. After resuscitation, blood cytokine levels were measured. The lung was then excised and ventilated with a tidal volume of 30 mL/kg for 2 hrs. RESULTS: The volume of fluids required was significantly smaller in the albumin-treated groups than in the Ringer's lactate groups. In the hemorrhagic shock model, plasma concentrations of tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2 were significantly lower and interleukin-10 was significantly higher in the albumin-treated groups compared with the Ringer's lactate-treated group. The levels of tumor necrosis factor-alpha and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were lower and interleukin-10 was higher in the albumin-treated groups than in the Ringer's lactate group. The decreased cytokine production was associated with a reduction of hydrogen peroxide formation with albumin resuscitation. The lung wet/dry ratio was lower in the 5% albumin (0.54 +/- 0.01) and 25% albumin (0.55 +/- 0.02) groups than in the Ringer's lactate group (0.62 +/- 0.02; both p <.05). These effects of albumin seen in the hemorrhagic shock model were not observed in the endotoxic shock model. CONCLUSIONS: We conclude that resuscitation with albumin may have utility in reducing ventilator-induced lung injury after hemorrhagic shock, but not after endotoxic shock. These findings suggest that the mechanisms leading to ventilator-induced lung injury after hemorrhage differ from those after endotoxemia.     

Feasibility of machine learning based predictive modelling of postoperative hyponatremia after pituitary surgery

Purpose

Hyponatremia after pituitary surgery is a frequent finding with potential severe complications and the most common cause for readmission. Several studies have found parameters associated with postoperative hyponatremia, but no reliable specific predictor was described yet. This pilot study evaluates the feasibility of machine learning (ML) algorithms to predict postoperative hyponatremia after resection of pituitary lesions.

Methods

Retrospective screening of a prospective registry of patients who underwent transsphenoidal surgery for pituitary lesions. Hyponatremia within 30 days after surgery was the primary outcome. Several pre- and intraoperative clinical, procedural and laboratory features were selected to train different ML algorithms. Trained models were compared using common performance metrics. Final model was internally validated on the testing dataset.

Results

From 207 patients included in the study, 44 (22%) showed a hyponatremia within 30 days postoperatively. Hyponatremic measurements peaked directly postoperatively (day 0–1) and around day 7. Bootstrapped performance metrics of different trained ML-models showed largest area under the receiver operating characteristic curve (AUROC) for the boosted generalized linear model (67.1%), followed by the Naïve Bayes classifier (64.6%). The discriminative capability of the final model was assessed by predicting on unseen dataset. Large AUROC (84.3%; 67.0–96.4), sensitivity (81.8%) and specificity (77.5%) with an overall accuracy of 78.4% (66.7–88.2) was reached.

Conclusion

Our trained ML-model was able to learn the complex risk factor interactions and showed a high discriminative capability on unseen patient data. In conclusion, ML-methods can predict postoperative hyponatremia and thus potentially reduce morbidity and improve patient safety.

     

Diabetes insipidus and syndrome of inappropriate antidiuresis (SIADH) after pituitary surgery: incidence and risk factors

Electrolyte disorders are relatively frequent and potentially serious complications after pituitary surgery. Both DI (diabetes insipidus) and SIADH (syndrome of inappropriate antidiuresis) can complicate and prolong hospital and intensive care unit stay, and the latter may even be preventable. We aim to assess the incidence of both electrolyte disorders and their risk factors. From a prospective registry of patients who underwent endoscopic transnasal transsphenoidal surgery (TSS) for pituitary adenoma, patients with postoperative DI and SIADH were identified. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of either DI or SIADH. A total of 174 patients were included, of which 73 (42%) were female. Mean age was 54 years (range 20–88). During postoperative hospital stay, 13 (7.5%) patients presenting with DI and 11 (6.3%) with SIADH were identified. Patients who developed DI after surgery had significantly longer hospital stays (p?=?0.022), as did those who developed SIADH (p?=?0.002). Four (2.3%) patients were discharged with a diagnosis of persistent DI, and 2 (1.1%) with the diagnosis of SIADH. At the last follow-up, 5 (2.9%) patients presented with persistent DI, while none of the patients suffered from SIADH. Younger age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94–1.01, p?=?0.166) and pituitary apoplexy (OR 2.69, 95% CI 0.53–10.65, p?=?0.184) were weakly associated with the occurrence of DI. We identified younger age (OR 0.96, 95% CI 0.92–0.99, p?=?0.045) and lower preoperative serum sodium (OR 0.83, 95% CI 0.71–0.95, p?=?0.008) as independent risk factors for SIADH. Although we found a weak association among age, pituitary apoplexy, and the occurrence of DI, no independent predictor was identified for DI. For postoperative SIADH however, lower age and preoperative serum sodium were identified as significant predictors. None of these findings were sufficiently supported by preexisting literature. Both electrolyte disorders are exquisitely hard to predict preoperatively, and further research into their early detection and prevention is warranted.

     

Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

Antimicrobial human neutrophil peptides (HNPs) play a pivotal role in innate host defense against a broad spectrum of prokaryotic pathogens. In addition, HNPs modulate cellular immune responses by producing the chemokine interleukin-8 (IL-8) in myeloid and epithelial cells and by exerting chemotaxis to T cells, immature dendritic cells, and monocytes. However, the mechanisms by which HNPs modulate the immune responses in the eukaryotic cells remain unclear. We demonstrated that, as with adenosine triphosphate (ATP) and uridine diphosphate (UDP), HNP stimulation of human lung epithelial cells selectively induced IL-8 production in 10 pro- and anti-inflammatory cytokines examined. HNP-induced IL-8 release was inhibited by treatment with the nucleotide receptor antagonists suramin and reactive blue. Transfection of lung epithelial cells with antisense oligonucleotides targeting specific purinergic P2Y receptors revealed that the P2Y6 (ligand of UDP) signaling pathway plays a predominant role in mediating HNP-induced IL-8 production.     

Imaging of Caenorhabditis elegans neurons by second-harmonic generation and two-photon excitation fluorescence

Second-harmonic generation (SHG) and two-photon excitation fluorescence (TPEF) are relatively new and promising tools for the detailed imaging of biological samples and processes at the microscopic level. By exploiting these nonlinear phenomena phototoxicity and photobleaching effects on the specimens are reduced dramatically. The main target of this work was the development of a compact inexpensive and reliable experimental apparatus for nonlinear microscopy measurements. Femtosecond laser pulses were utilized for excitation. We achieved high-resolution imaging and mapping of Caenorhabditis elegans (C. elegans) neurons and muscular structures of the pharynx, at the microscopic level by performing SHG and TPEF measurements. By detecting nonlinear phenomena such as SHG and TPEF it is feasible to extract valuable information concerning the structure and the function of nematode neurons.     

Inducible H-2M and constitutive H-2O/H-2A expression on trophoblast cells

Trophoblast cells escape maternal immune attack due to their class II negative state. This generally accepted hypothesis, however, became complicated when these antigens were shown induced by IFN-γ, 5-AzaC, LPS, mycobacterium and other factors, an expression correlated, as expected, to fetal abortion. Using untreated trophoblast cells as controls in the study of class II antigen regulation we found that, although the cells were not expressing surface class II molecules, they contained class II positive intracellular pools, which after short treatment with IFN could be emptied to the culture supernatants. Using immunofluorescence, ELISA, confocal microscopy, immunoaffinity purification, subcellular fractionation as well as Western blots and RT-PCR experiments we localized, identified the class II proteins in trophoblasts and studied their mechanisms of excretion. It was shown that classical class II molecules co-localized with the invariant chain in rab7 and rab11 positive endosomes and could be secreted from the cells via the endosomal pathway, since their extracellular detection could be inhibited by pepstatin, brefeldin and leupeptin. RT-PCR experiments using H-2M, H-2O and H-2A specific primers showed that H-2O and H-2A are constitutively expressed in trophoblasts, whereas H-2M is inducible by IFN. Cyclohexamide treatment blocked secretion of class II antigens from these cells indicating that H-2M is involved in the secretion and/or appearance to the membrane.     

Impact of additional resection on new ischemic lesions and their clinical relevance after intraoperative 3 Tesla MRI in neuro-oncological surgery

Neurosurgical Review - Intraoperative MRI (ioMRI) has become a frequently used tool to improve maximum safe resection in brain tumor surgery. The usability of intraoperatively acquired...