Case report of parapneumonic effusion and mesothelial subdiaphragmatic cyst: relationship or coincidence?

Parapneumonic pleural effusions are common in patients with pneumonia. When colonized by pathogenic bacteria or other microorganisms, these effusions can progress to empyema. Additionally, empyema formation may result in extension of the infection into the infradiaphragmatic region, further complicating the clinical scenario. Many subphrenic collections are found to be mesothelial cysts, which are congenital in origin. However, data regarding the potential association between mesothelial diaphragmatic cysts and parapneumonic effusions are limited. We herein describe a toddler with pneumonia complicated by parapneumonic effusion and a lung abscess with a subphrenic collection. After abscess drainage and a full course of antibiotics, imaging revealed clear lung parenchyma with an interval resolution of the effusion and a persistent unchanged subphrenic collection that was confirmed to be mesothelial diaphragmatic cyst. This case highlights the fact that not every subphrenic collection associated with parapneumonic effusion is a communicated collection formed by seeding. Such a collection can instead be an incidental cyst, which is congenital in origin and known as a mesothelial diaphragmatic cyst. A diaphragmatic mesothelial cyst is an uncommon benign congenital cyst that is unrelated to an adjacent parapneumonic effusion. It is usually incidental and can be monitored without invasive intervention.

Oil spill risk analysis for the NEOM shoreline.

A risk analysis is conducted considering an array of release sources located around the NEOM shoreline. The sources are selected close to the coast and in neighboring regions of high marine traffic. The evolution of oil spills released by these sources is simulated using the MOHID model, driven by validated, high-resolution met-ocean fields of the Red Sea. For each source, simulations are conducted over a 4-week period, starting from first, tenth and twentieth days of each month, covering five consecutive years. A total of 180 simulations are thus conducted for each source location, adequately reflecting the variability of met-ocean conditions in the region. The risk associated with each source is described in terms of amount of oil beached, and by the time required for the spilled oil to reach the NEOM coast, extending from the Gulf of Aqaba in the North to Duba in the South. To further characterize the impact of individual sources, a finer analysis is performed by segmenting the NEOM shoreline, based on important coastal development and installation sites. For each subregion, source and release event considered, a histogram of the amount of volume beached is generated, also classifying individual events in terms of the corresponding arrival times. In addition, for each subregion considered, an inverse analysis is conducted to identify regions of dependence of the cumulative risk, estimated using the collection of all sources and events considered. The transport of oil around the NEOM shorelines is promoted by chaotic circulations and northwest winds in summer, and a dominant cyclonic eddy in winter. Hence, spills originating from release sources located close to the NEOM shorelines are characterized by large monthly variations in arrival times, ranging from less than a week to more than 2 weeks. Similarly, large variations in the volume fraction of beached oil, ranging from less then 50% to more than 80% are reported. The results of this study provide key information regarding the location of dominant oil spill risk sources, the severity of the potential release events, as well as the time frames within which mitigation actions may need to deployed.

Arachidonic acid, a clinically adverse mediator in the ovarian cancer microenvironment, impairs JAK-STAT signaling in macrophages by perturbing lipid raft structures.

Survival of ovarian carcinoma is associated with the abundance of immunosuppressed CD163high CD206high tumor-associated macrophages (TAMs) and high levels of arachidonic acid (AA) in the tumor microenvironment. Here, we show that both associations are functionally linked. Transcriptional profiling revealed that high CD163 and CD206/MRC1 expression in TAMs is strongly associated with an inhibition of cytokine-triggered signaling, mirrored by an impaired transcriptional response to interferons and IL-6 in monocyte-derived macrophages by AA. This inhibition of pro-inflammatory signaling is caused by dysfunctions of the cognate receptors, indicated by the inhibition of JAK1, JAK2, STAT1, and STAT3 phosphorylation, and by the displacement of the interferon receptor IFNAR1, STAT1 and other immune-regulatory proteins from lipid rafts. AA exposure led to a dramatic accumulation of free AA in lipid rafts, which appears to be mechanistically crucial, as the inhibition of its incorporation into phospholipids did not affect the AA-mediated interference with STAT1 phosphorylation. Inhibition of interferon-triggered STAT1 phosphorylation by AA was reversed by water-soluble cholesterol, known to prevent the perturbation of lipid raft structure by AA. These findings suggest that the pharmacologic restoration of lipid raft functions in TAMs may contribute to the development new therapeutic approaches.

Identifying effective retention strategies for front-line nurses.

BACKGROUND: Nurse retention is a significant issue worldwide, with many nurses planning to leave the profession. Therefore, it is crucial that healthcare organisations and senior leaders identify effective strategies for retaining their employees, who are their most valuable assets. AIM: To explore strategies to reduce the voluntary turnover of front-line nurses from the perspective of senior healthcare leaders. METHOD: This study used a case study design and a qualitative approach. Semi-structured interviews were conducted with six senior leaders in one US hospital and documents from the organisation's website were reviewed to gain information on the retention strategies used. FINDINGS: Three themes were identified from the data: job satisfaction, financial compensation and effective communication. Retention strategies used by the senior leaders included a points competition to support recognition of nurses' work, a stoplight strategy and reports, sign-on bonuses, preceptor incentives, tuition reimbursements, staff shout-out boards and stay interviews. CONCLUSION: Effective communication, respect, competitive financial compensation, benefits and proper recognition are among the main strategies that senior leaders can use to retain nurses. Shared governance is also important in empowering nurses and subsequently improving retention.

COVID-19 associated respiratory failure complicating a pericardial effusion in a patient with sideroblastic anemia.

BACKGROUND: COVID-19 disease has been associated with several cardiovascular complications that rarely occur in the acute phase of the disease. CASE REPORT: A 13-year-old pediatric patient with congenital sideroblastic anemia associated with YARS2 mutation presenting with COVID-19 infection and worsening pericardial effusion followed by a respiratory failure refractory to supplemental oxygen therapy leading to cardiac arrest. DISCUSSION: This case highlights the rapid deterioration that can occur in children with serious hematologic disorders in the context of COVID-19 especially when complicated with pericardial effusion. CONCLUSION: The importance of pericardiocentesis early in order to allow better ventilation in any significant pericardial effusion case associated with COVID-19 infection and the need for prompt care escalation to centers where ECMO is available.

Phosphoproteomics identify arachidonic-acid-regulated signal transduction pathways modulating macrophage functions with implications for ovarian cancer.

Arachidonic acid (AA) is a polyunsaturated fatty acid present at high concentrations in the ovarian cancer (OC) microenvironment and associated with a poor clinical outcome. In the present study, we have unraveled a potential link between AA and macrophage functions. Methods: AA-triggered signal transduction was studied in primary monocyte-derived macrophages (MDMs) by phosphoproteomics, transcriptional profiling, measurement of intracellular Ca2+ accumulation and reactive oxygen species production in conjunction with bioinformatic analyses. Functional effects were investigated by actin filament staining, quantification of macropinocytosis and analysis of extracellular vesicle release. Results: We identified the ASK1 - p38δ/α (MAPK13/14) axis as a central constituent of signal transduction pathways triggered by non-metabolized AA. This pathway was induced by the Ca2+-triggered activation of calmodulin kinase II, and to a minor extent by ROS generation in a subset of donors. Activated p38 in turn was linked to a transcriptional stress response associated with a poor relapse-free survival. Consistent with the phosphorylation of the p38 substrate HSP27 and the (de)phosphorylation of multiple regulators of Rho family GTPases, AA impaired actin filament organization and inhibited actin-driven macropinocytosis. AA also affected the phosphorylation of proteins regulating vesicle biogenesis, and consistently, AA enhanced the release of tetraspanin-containing exosome-like vesicles. Finally, we identified phospholipase A2 group 2A (PLA2G2A) as the clinically most relevant enzyme producing extracellular AA, providing further potentially theranostic options. Conclusion: Our results suggest that AA contributes to an unfavorable clinical outcome of OC by impacting the phenotype of tumor-associated macrophages. Besides critical AA-regulated signal transduction proteins identified in the present study, PLA2G2A might represent a potential prognostic tool and therapeutic target to interfere with OC progression.

Raman micro-spectroscopy monitors acquired resistance to targeted cancer therapy at the cellular level.

Monitoring the drug efficacy or resistance in vitro is usually carried out by measuring the response of single few proteins. However, observation of single proteins instead of an integral cell response may lead to results that are not consistent with patient's response to a drug. We present a Raman spectroscopic method that detects the integral cell response to drugs such as tyrosine kinase inhibitors (TKIs). Non-small cell lung cancer (NSCLC) patients with EGFR mutations develop acquired resistance to first (erlotinib)- and third (osimertinib)-generation TKIs. Large erlotinib-induced differences were detected by Raman micro-spectroscopy in NSCLC cells without T790M EGFR mutation but not in cells with this mutation. Additionally, Raman difference spectra detected the response of NSCLC cells with T790M EGFR mutation to second- (neratinib) and third-generation (osimertinib) TKIs, and the resistance of cells with T790M/C797S EGFR mutation to osimertinib. Thus, the in vitro Raman results indicated that NSCLC cells with T790M and T790M/C797S EGFR mutations are resistant to erlotinib- and osimertinib, respectively, consistent with the observed responses of patients. This study shows the potential of Raman micro-spectroscopy to monitor drug resistance and opens a new door to in vitro companion diagnostics for screening personalized therapies.

Raman Microspectroscopic Evidence for the Metabolism of a Tyrosine Kinase Inhibitor, Neratinib, in Cancer Cells.

Tyrosine kinase receptors are one of the main targets in cancer therapy. They play an essential role in the modulation of growth factor signaling and thereby inducing cell proliferation and growth. Tyrosine kinase inhibitors such as neratinib bind to EGFR and HER2 receptors and exhibit antitumor activity. However, little is known about their detailed cellular uptake and metabolism. Here, we report for the first time the intracellular spatial distribution and metabolism of neratinib in different cancer cells using label-free Raman imaging. Two new neratinib metabolites were detected and fluorescence imaging of the same cells indicate that neratinib accumulates in lysosomes. The results also suggest that both EGFR and HER2 follow the classical endosome lysosomal pathway for degradation. A combination of Raman microscopy, DFT calculations, and LC-MS was used to identify the chemical structure of neratinib metabolites. These results show the potential of Raman microscopy to study drug pharmacokinetics.