Development of a predictive model for risk stratification of acute kidney injury in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Acute kidney injury (AKI) following hyperthermic intraperitoneal chemotherapy (HIPEC) is common. Identifying patients at risk could have implications for surgical and anesthetic management. We aimed to develop a predictive model that could predict AKI based on patients' preoperative characteristics and intraperitoneal chemotherapy regimen. We retrospectively gathered data of adult patients undergoing HIPEC at our health system between November 2013 and April 2022. Next, we developed a model predicting postoperative AKI using multivariable logistic regression and calculated the performance of the model (area under the receiver operating characteristics curve [AUC]) via tenfold cross-validation. A total of 412 patients were included, of which 36 (8.7%) developed postoperative AKI. Based on our multivariable logistic regression model, multiple preoperative and intraoperative characteristics were associated with AKI. We included the total intraoperative cisplatin dose, body mass index, male sex, and preoperative hemoglobin level in the final model. The mean area under the receiver operating characteristics curve value was 0.82 (95% confidence interval 0.71-0.93). Our risk model predicted AKI with high accuracy in patients undergoing HIPEC in our institution. The external validity of our model should now be tested in independent and prospective patient cohorts.

"In Safe Hands" - A costly integrated care program with limited benefits in stroke unit care.

Given reported favourable outcomes of accountable care unit models of health care delivery (Taylor et al., 2017; Stein et al., 2015; Kara et al., 2015), the Clinical Excellence Commission of NSW has embraced "In Safe Hands" (ISH) to enhance coordination of care. ISH embraces the structured interdisciplinary bedside round (SIBR) component, for which reported outcomes include reduced length of stay (Taylor et al., 2017; Stein et al., 2015; Kara et al., 2015), possible reduction in overall costs of care (Kara et al., 2015), and enhanced patient and staff satisfaction (O'Leary et al., 2011). It is not yet clear whether the benefits of such a model are translatable to the Australian Health Care System (Hunyh et al., 2016) and/or established units with an already strong multi-disciplinary approach to patient care. The purpose of this prospective cohort study of 200 participants was to assess the effect(s) of implementation of ISH in a stroke unit of a tertiary hospital in Sydney, Australia. Data on length of stay, re-admission rates, adverse events, as well as patient and nursing satisfaction, were collected pre and post implementation. There was no significant difference in length of stay in median days (5 (IQR 2-7) versus 4 (IQR 2-6), P = 0.55) or incidence of adverse events (10% versus 12%, P = 0.82). Stroke outcome disability scores were not affected by the intervention. There were no significant differences overall in reported patient and nursing satisfaction. Implementation of the ISH program cost approximately AUD$ 1805/week (USD$ 1365) in wages. The ISH program was a costly intervention of limited benefit in a well-established acute stroke unit. We here discuss potential reasons for the failure of this intervention to achieve its primary aim in this setting.

Novel therapeutic roles for surfactant-inositols and -phosphatidylglycerols in a neonatal piglet ARDS model: a translational study.

The biological and immune-protective properties of surfactant-derived phospholipids and phospholipid subfractions in the context of neonatal inflammatory lung disease are widely unknown. Using a porcine neonatal triple-hit acute respiratory distress syndrome (ARDS) model (repeated airway lavage, overventilation, and LPS instillation into airways), we assessed whether the supplementation of surfactant (S; poractant alfa) with inositol derivatives [inositol 1,2,6-trisphosphate (IP3) or phosphatidylinositol 3,5-bisphosphate (PIP2)] or phosphatidylglycerol subfractions [16:0/18:1-palmitoyloleoyl-phosphatidylglycerol (POPG) or 18:1/18:1-dioleoyl-phosphatidylglycerol (DOPG)] would result in improved clinical parameters and sought to characterize changes in key inflammatory pathways behind these improvements. Within 72 h of mechanical ventilation, the oxygenation index (S+IP3, S+PIP2, and S+POPG), the ventilation efficiency index (S+IP3 and S+POPG), the compliance (S+IP3 and S+POPG) and resistance (S+POPG) of the respiratory system, and the extravascular lung water index (S+IP3 and S+POPG) significantly improved compared with S treatment alone. The inositol derivatives (mainly S+IP3) exerted their actions by suppressing acid sphingomyelinase activity and dependent ceramide production, linked with the suppression of the inflammasome nucleotide-binding domain, leucine-rich repeat-containing protein-3 (NLRP3)-apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-caspase-1 complex, and the profibrotic response represented by the cytokines transforming growth factor-ß1 and IFN-γ, matrix metalloproteinase (MMP)-1/8, and elastin. In addition, IκB kinase activity was significantly reduced. S+POPG and S+DOPG treatment inhibited polymorphonuclear leukocyte activity (MMP-8 and myeloperoxidase) and the production of interleukin-6, maintained alveolar-capillary barrier functions, and reduced alveolar epithelial cell apoptosis, all of which resulted in reduced pulmonary edema. S+DOPG also limited the profibrotic response. We conclude that highly concentrated inositol derivatives and phosphatidylglycerol subfractions in surfactant preparations mitigate key inflammatory pathways in inflammatory lung disease and that their clinical application may be of interest for future treatment of the acute exudative phase of neonatal ARDS.

Toward engineering intra-receptor interactions into bis(crown ethers).

A synthetic receptor was designed in which cooperative binding of two crown ether moieties to an alkali metal ion simultaneously causes two hydrophobic substituents not involved in direct host-guest interactions to converge. Hydrophobic interactions between these substituents can be expected to contribute to the overall complex stability. Independent binding studies involving two diastereoisomers of this bis(crown ether), one in which intra-receptor interactions between the substituents are potentially possible and one in which they are not, using isothermal titration calorimetry showed that both isomers bind potassium ions in different solvent mixtures with the same overall affinity. Profound differences were observed for each isomer, however, in the enthalpies and entropies of binding, which are consistent with intra-receptor interactions in one compound. These interactions are counteracted by enthalpy-entropy compensation so that no overall improvement in cation affinity could be observed.

Chronic inhibition of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a popular treatment option for patients suffering from severe Parkinson's disease (PD). Yet the long-term outcome of subthalamic DBS is unknown. A total of 27 patients suffering from severe PD underwent bilateral stereotactic implantation of high-frequency stimulators in the STN. Before surgery and at least annually after surgery they were examined with the Unified Parkinson's Disease Rating Scale (UPDRS). This study presents the results of a mean 30 months (range 23 to 55) follow-up of these patients. We found stable and significant off medication improvement of motor function by DBS (between 40% and 44% in the UPDRS part III). While on medication there was no significant change in the motor function by DBS. UPDRS part III worsened gradually during the follow-up period, suggesting disease progression. Thirty months postsurgery the UPDRS part II (ADL) was still improved by 17%. There was a lasting decrease in fluctuations by more than 50%, and dyskinesias were reduced by about 70%. Freezing was reduced significantly from 2.2 in the UPDRS part II to 1.2 at the endpoint. The daily levodopa-equivalent dose was reduced by 39% at 12 months and by 30% at 30 months after STN stimulator implantation. Subthalamic DBS improves sustainable motor function in patients with severe Parkinson's disease and leads to a lasting reduction of medication. Limitations of this procedure were found for disturbances of speech and swallowing.

Subthalamic nucleus stimulation affects a frontotemporal network: a PET study.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective strategy in the treatment of motor symptoms in advanced Parkinson's disease. However, clinical studies have shown that DBS can affect verbal fluency. Seven Parkinson's disease patients with bilateral DBS of the STN were studied with positron emission tomography (PET) to investigate the effects of STN stimulation on regional cerebral blood flow during a verbal fluency task. Activation of the right orbitofrontal cortex and verbal fluency-associated activation within a left-sided frontotemporal network were decreased during STN stimulation compared with the OFF state. Our results offer an explanation for the commonest neuropsychological side effect of STN stimulation and show that STN stimulation affects a frontotemporal network during a fluency task.