Association Between Chest Compression Pause Duration and Survival After Pediatric In-Hospital Cardiac Arrest.

BACKGROUND: The association between chest compression (CC) pause duration and pediatric in-hospital cardiac arrest survival outcomes is unknown. The American Heart Association has recommended minimizing pauses in CC in children to <10 seconds, without supportive evidence. We hypothesized that longer maximum CC pause durations are associated with worse survival and neurological outcomes. METHODS: In this cohort study of index pediatric in-hospital cardiac arrests reported in pediRES-Q (Quality of Pediatric Resuscitation in a Multicenter Collaborative) from July of 2015 through December of 2021, we analyzed the association in 5-second increments of the longest CC pause duration for each event with survival and favorable neurological outcome (Pediatric Cerebral Performance Category ≤3 or no change from baseline). Secondary exposures included having any pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds per 2 minutes. RESULTS: We identified 562 index in-hospital cardiac arrests (median [Q1, Q3] age 2.9 years [0.6, 10.0], 43% female, 13% shockable rhythm). Median length of the longest CC pause for each event was 29.8 seconds (11.5, 63.1). After adjustment for confounders, each 5-second increment in the longest CC pause duration was associated with a 3% lower relative risk of survival with favorable neurological outcome (adjusted risk ratio, 0.97 [95% CI, 0.95-0.99]; P=0.02). Longest CC pause duration was also associated with survival to hospital discharge (adjusted risk ratio, 0.98 [95% CI, 0.96-0.99]; P=0.01) and return of spontaneous circulation (adjusted risk ratio, 0.93 [95% CI, 0.91-0.94]; P<0.001). Secondary outcomes of any pause >10 seconds or >20 seconds and number of CC pauses >10 seconds and >20 seconds were each significantly associated with adjusted risk ratio of return of spontaneous circulation, but not survival or neurological outcomes. CONCLUSIONS: Each 5-second increment in longest CC pause duration during pediatric in-hospital cardiac arrest was associated with lower chance of survival with favorable neurological outcome, survival to hospital discharge, and return of spontaneous circulation. Any CC pause >10 seconds or >20 seconds and number of pauses >10 seconds and >20 seconds were significantly associated with lower adjusted probability of return of spontaneous circulation, but not survival or neurological outcomes.

Reduction of CO to Methanol with Recyclable Organic Hydrides.

The reaction steps for the selective conversion of a transition metal carbonyl complex to a hydroxymethyl complex that releases methanol upon irradiation with visible light have been successfully quantified in acetonitrile solution with dihydrobenzimidazole organic hydride reductants. Dihydrobenzimidazole reductants have been shown to be inactive toward H2 generation in the presence of a wide range of proton sources and have been regenerated electrochemically or photochemically. Specifically, the reaction of cis-[Ru(bpy)2(CO)2]2+ (bpy = 2,2'-bipyridine) with one equivalent of a dihydrobenzimidazole quantitatively yields a formyl complex, cis-[Ru(bpy)2(CO)(CHO)]+, and the corresponding benzimidazolium on a seconds time scale. Kinetic experiments revealed a first-order dependence on the benzimidazole hydride concentration and an unusually large kinetic isotope effect, inconsistent with direct hydride transfer and more likely to occur by an electron transfer-proton-coupled electron transfer (EΤ-PCET) or related mechanism. Further reduction/protonation of cis-[Ru(bpy)2(CO)(CHO)]+ with two equivalents of the organic hydride yields the hydroxymethyl complex cis-[Ru(bpy)2(CO)(CH2OH)]+. Visible light excitation of cis-[Ru(bpy)2(CO)(CH2OH)]+ in the presence of excess organic hydride was shown to yield free methanol. Identification and quantification of methanol as the sole CO reduction product was confirmed by 1H NMR spectroscopy and gas chromatography. The high selectivity and mild reaction conditions suggest a viable approach for methanol production from CO, and from CO2 through cascade catalysis, with renewable organic hydrides that bear similarities to Nature's NADPH/NADP+.

Higher Survival With the Use of Extracorporeal Cardiopulmonary Resuscitation Compared With Conventional Cardiopulmonary Resuscitation in Children Following Cardiac Surgery: Results of an Analysis of the Get With The Guidelines-Resuscitation Registry.

OBJECTIVES: Extracorporeal membrane oxygenation to support cardiopulmonary resuscitation (CPR) is increasingly used in children suffering cardiac arrest after cardiac surgery. However, its efficacy in promoting survival has not been evaluated. We compared survival of pediatric cardiac surgery patients suffering in-hospital cardiac arrest who were resuscitated with extracorporeal CPR (E-CPR) to those resuscitated with conventional CPR (C-CPR) using propensity matching. DESIGN: Retrospective study using multicenter data from the American Heart Association Get With The Guidelines-Resuscitation registry (2008-2020). SETTING: Multicenter cardiac arrest database containing cardiac arrest and CPR data from U.S. hospitals. PATIENTS: Cardiac surgical patients younger than 18 years old who suffered in-hospital cardiac arrest and received greater than or equal to 10 minutes of CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1223 patients, 741 (60.6%) received C-CPR and 482 (39.4%) received E-CPR. E-CPR utilization increased over the study period ( p < 0.001). Duration of CPR was longer in E-CPR compared with C-CPR recipients (42 vs. 26 min; p < 0.001). In a propensity score matched cohort (382 E-CPR recipients, 382 C-CPR recipients), E-CPR recipients had survival to discharge (odds ratio [OR], 2.22; 95% CI, 1.7-2.9; p < 0.001). E-CPR survival was only higher when CPR duration was greater than 18 minutes. Propensity matched analysis using patients from institutions contributing at least one E-CPR case ( n = 35 centers; 353 E-CPR recipients, 353 C-CPR recipients) similarly demonstrated improved survival in E-CPR recipients compared with those who received C-CPR alone (OR, 2.08; 95% CI, 1.6-2.8; p < 0.001). CONCLUSIONS: E-CPR compared with C-CPR improved survival in children suffering cardiac arrest after cardiac surgery requiring CPR greater than or equal to 10 minutes.

Cerebral Oximetry During Pediatric In-Hospital Cardiac Arrest: A Multicenter Study of Survival and Neurologic Outcome.

OBJECTIVES: To determine if near-infrared spectroscopy measuring cerebral regional oxygen saturation (crS o2 ) during cardiopulmonary resuscitation is associated with return of spontaneous circulation (ROSC) and survival to hospital discharge (SHD) in children. DESIGN: Multicenter, observational study. SETTING: Three hospitals in the pediatric Resuscitation Quality (pediRES-Q) collaborative from 2015 to 2022. PATIENTS: Children younger than 18 years, gestational age 37 weeks old or older with in-hospital cardiac arrest (IHCA) receiving cardiopulmonary resuscitation greater than or equal to 1 minute and intra-arrest crS o2 monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was ROSC greater than or equal to 20 minutes without extracorporeal membrane oxygenation. Secondary outcomes included SHD and favorable neurologic outcome (FNO) (Pediatric Cerebral Performance Category 1-2 or no change from prearrest). Among 3212 IHCA events (index and nonindex), 123 met inclusion criteria in 93 patients. Median age was 0.3 years (0.1-1.4 yr) and 31% (38/123) of the cardiopulmonary resuscitation events occurred in patients with cyanotic heart disease. Median cardiopulmonary resuscitation duration was 8 minutes (3-28 min) and ROSC was achieved in 65% (80/123). For index events, SHD was achieved in 59% (54/91) and FNO in 41% (37/91). We determined the association of median intra-arrest crS o2 and percent of crS o2 values above a priori thresholds during the: 1) entire cardiopulmonary resuscitation event, 2) first 5 minutes, and 3) last 5 minutes with ROSC, SHD, and FNO. Higher crS o2 for the entire cardiopulmonary resuscitation event, first 5 minutes, and last 5 minutes were associated with higher likelihood of ROSC, SHD, and FNO. In multivariable analysis of the infant group (age < 1 yr), higher crS o2 was associated with ROSC (odds ratio [OR], 1.06; 95% CI, 1.03-1.10), SHD (OR, 1.04; 95% CI, 1.01-1.07), and FNO (OR, 1.05; 95% CI, 1.02-1.08) after adjusting for presence of cyanotic heart disease. CONCLUSIONS: Higher crS o2 during pediatric IHCA was associated with increased rate of ROSC, SHD, and FNO. Intra-arrest crS o2 may have a role as a real-time, noninvasive predictor of ROSC.

Outcomes of Extracorporeal Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest Among Children With Noncardiac Illness Categories.

OBJECTIVES: The objective of this study was to determine the association of the use of extracorporeal cardiopulmonary resuscitation (ECPR) with survival to hospital discharge in pediatric patients with a noncardiac illness category. A secondary objective was to report on trends in ECPR usage in this population for 20 years. DESIGN: Retrospective multicenter cohort study. SETTING: Hospitals contributing data to the American Heart Association's Get With The Guidelines-Resuscitation registry between 2000 and 2021. PATIENTS: Children (<18 yr) with noncardiac illness category who received greater than or equal to 30 minutes of cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Propensity score weighting balanced ECPR and conventional CPR (CCPR) groups on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model estimated the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR utilization. Of 875 patients, 159 received ECPR and 716 received CCPR. The median age was 1.0 [interquartile range: 0.2-7.0] year. Most patients (597/875; 68%) had a primary diagnosis of respiratory insufficiency. Median CPR duration was 45 [35-63] minutes. ECPR use increased over time ( p < 0.001). We did not identify differences in survival to discharge between the ECPR group (21.4%) and the CCPR group (16.2%) in univariable analysis ( p = 0.13) or propensity-weighted multivariable logistic regression (adjusted odds ratio 1.42 [95% CI, 0.84-2.40; p = 0.19]). The Bayesian model estimated an 85.1% posterior probability of a positive effect of ECPR on survival to discharge. CONCLUSIONS: ECPR usage increased substantially for the last 20 years. We failed to identify a significant association between ECPR and survival to hospital discharge, although a post hoc Bayesian analysis suggested a survival benefit (85% posterior probability).

Contemporary Care and Outcomes of Critically-ill Children With Clinically Diagnosed Myocarditis.

PURPOSE: To describe contemporary management and outcomes in children with myocarditis who are admitted to a cardiac intensive care unit (CICU) and to identify the characteristics associated with mortality. METHODS: All patients in the Pediatric Cardiac Critical Care Consortium (PC4) registry between August 2014 and June 2021 who were diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated the factors associated with in-hospital mortality. RESULTS: There were 847 CICU admissions for myocarditis in 51 centers. The median age was 12 years (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%), and 60 (7.1%) had cardiac arrest during admission. Mechanical ventilation was required in 339 patients (40%), and mechanical circulatory support (MCS) in 177 (21%); extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation in 43 (5%), and VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (P < 0.001). Mortality rates were similar in ECMO-only, ECMO-to-VAD and VAD-only groups. The median time from CICU admission to ECMO was 2.0 hours (IQR 0-9.4) and to VAD, it was 9.9 days (IQR 6.3-16.8). Time to MCS was not associated with mortality. In multivariable modeling of patients' characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation and ECMO were independent predictors of mortality. CONCLUSION: This contemporary cohort of children admitted to CICUs with myocarditis commonly received high-resource therapies; however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury and receipt of mechanical ventilation or ECMO were independently associated with mortality.

Repression of the Hox gene abd-A by ELAV-mediated Transcriptional Interference.

Intergenic transcription is a common feature of eukaryotic genomes and performs important and diverse cellular functions. Here, we investigate the iab-8 ncRNA from the Drosophila Bithorax Complex and show that this RNA is able to repress the transcription of genes located at its 3' end by a sequence-independent, transcriptional interference mechanism. Although this RNA is expressed in the early epidermis and CNS, we find that its repressive activity is limited to the CNS, where, in wild-type embryos, it acts on the Hox gene, abd-A, located immediately downstream of it. The CNS specificity is achieved through a 3' extension of the transcript, mediated by the neuronal-specific, RNA-binding protein, ELAV. Loss of ELAV activity eliminates the 3' extension and results in the ectopic activation of abd-A. Thus, a tissue-specific change in the length of a ncRNA is used to generate a precise pattern of gene expression in a higher eukaryote.

A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

Post-operative dysnatremia is associated with adverse early outcomes after surgery for congenital heart disease.

BACKGROUND: Dysnatremia is a common disorder in critically ill surgical children. The study's aim is to determine the prevalence of dysnatremia and its association with outcomes after surgery for congenital heart disease (CHD). METHODS: This is a single-center retrospective cohort study of children <18 years of age undergoing surgery for CHD between January 2012 and December 2014. Multivariable logistic regression analysis was used to evaluate the relationship between dysnatremia and outcomes during the perioperative period. A total of 1345 encounters met the inclusion criteria. RESULTS: The prevalence of pre- and post-operative dysnatremia were 10.2% and 47.1%, respectively. Hyponatremia occurred in 19.1%, hypernatremia in 25.6%. Hypernatremia at 24, 48, and 72 h post-operative was associated with increased hospital mortality (odds ratios (OR) [95% confidence intervals (CI)] 3.08 [1.16-8.17], p = 0.024; 4.35 [1.58-12], p = 0.0045; 4.14 [1.32-12.97], p = 0.0148, respectively. Hypernatremia was associated with adverse neurological events 3.39 [1.12-10.23], p = 0.0302 at 48 h post-operative. Hyponatremia was not associated with any adverse outcome in our secondary analysis. CONCLUSIONS: Post-operative dysnatremia is a common finding in this heterogeneous cohort of pediatric cardiac-surgical patients. Hypernatremia was more prevalent than hyponatremia and was associated with adverse early post-operative outcomes. IMPACT: Our study has shown that dysnatremia was highly prevalent in children after congenital heart surgery with hypernatremia associated with adverse outcomes including mortality. It is important to understand fluid and sodium regulation in the post-operative period in children with congenital heart disease to better address fluid overload and associated electrolyte imbalances and acute kidney injury. While clinicians are generally very aware of the importance of hyponatremia in critically ill children, similar attention should be given to hypernatremia in this population.

Identification of new hit to lead magmas inhibitors as potential therapeutics for glioblastoma.

In continuation of our previous efforts for the development of potent small molecules against brain cancer, herein we synthesized seventeen new compounds and tested their anti-gliomapotential against established glioblastoma cell lines, namely, D54MG, U251, and LN-229 as well as patient derived cell lines (DB70 and DB93). Among them, the carboxamide derivatives, BT-851 and BT-892 were found to be the most active leads in comparison to our established hit compound BT#9.The SAR studies of our hit BT#9 compound resulted in the development of two new lead compounds by hit to lead strategy. The detailed biological studies are currently underway. The active compounds could possibly act as template for the future development of newer anti-glioma agents.

Synthesis and Surface Attachment of Molecular Re(I) Complexes Supported by Functionalized Bipyridyl Ligands.

Eleven 2,2'-bipyridine (bpy) ligands functionalized with attachment groups for covalent immobilization on silicon surfaces were prepared. Five of the ligands feature silatrane functional groups for attachment to metal oxide coatings on the silicon surfaces, while six contain either alkene or alkyne functional groups for attachment to hydrogen-terminated silicon surfaces. The bpy ligands were coordinated to Re(CO)5Cl to form complexes of the type Re(bpy)(CO)3Cl, which are related to known catalysts for CO2 reduction. Six of the new complexes were characterized using X-ray crystallography. As proof of principle, four molecular Re complexes were immobilized on either a thin layer of TiO2 on silicon or hydrogen-terminated silicon. The surface-immobilized complexes were characterized using X-ray photoelectron spectroscopy, IR spectroscopy, and cyclic voltammetry (CV) in the dark and for one representative example in the light. The CO stretching frequencies of the attached complexes were similar to those of the pure molecular complexes, but the CVs were less analogous. For two of the complexes, comparison of the electrocatalytic CO2 reduction performance showed lower CO Faradaic efficiencies for the immobilized complexes than the same complex in solution under similar conditions. In particular, a complex containing a silatrane linked to bpy with an amide linker showed poor catalytic performance and control experiments suggest that amide linkers in conjugation with a redox-active ligand are not stable under highly reducing conditions and alkyl linkers are more stable. A conclusion of this work is that understanding the behavior of molecular Re catalysts attached to semiconducting silicon is more complicated than related complexes, which have previously been immobilized on metallic electrodes.

Gender Gap: A Qualitative Study of Women and Leadership Acquisition in Anesthesiology.

BACKGROUND: The representation of women among leaders in the field of anesthesia continues to trail that of their male counterparts. This qualitative study was conducted to understand the pathway of leadership acquisition among women in the field of anesthesiology. METHODS: Using constructivist grounded theory, we sought to determine whether there were specific internal or external factors that were common to women in leadership in the specialty field of anesthesiology, and specifically, how they obtained leadership positions. Semistructured interviews were conducted for data collection. A total of 26 women in leadership positions in anesthesiology participated in this study. RESULTS: The analysis of these interviews resulted in the development of 4 common themes related to career pathways for these women in leadership. Each theme was examined in depth to determine the qualities necessary for individuals to advance in the field and the pathway to obtaining leadership positions. The findings of this study showed that early-career, high-value mentorship and sponsorship were important factors in leadership acquisition. Most participants (n = 20; 76%) had early mentors. Of those with early mentorship, 13 (65%) had high-value mentors, who we define as someone with power or authority. Sponsorship was the leading factor contributing to leadership acquisition. CONCLUSIONS: The results of this qualitative study may serve as a guide for encouraging female anesthesiologists with leadership aspirations. We suggest that the specialty field of anesthesiology institute targeted measures to help increase the percentage of women leadership with formal sponsorship programs at the local and national levels.

Critical Care Unit Characteristics and Extracorporeal Cardiopulmonary Resuscitation Survival in the Pediatric Cardiac Population: Retrospective Analysis of the Virtual Pediatric System Database.

OBJECTIVES: Existing literature provides limited data about ICU characteristics and pediatric extracorporeal cardiopulmonary resuscitation (E-CPR) outcomes. We aimed to evaluate the associations between patient and ICU characteristics, and outcomes after E-CPR in the pediatric cardiac population. DESIGN: Retrospective analysis of the Virtual Pediatric System database (VPS, LLC, Los Angeles, CA). SETTING: PICUs categorized as either cardiac-only versus mixed ICU cohort type. PATIENTS: Consecutive cardiac patients less than 18 years old experiencing cardiac arrest in the ICU and resuscitated using E-CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Event and time-stamp filtering identified E-CPR events. Patient, hospital, and event-related variables were aggregated for independent and multivariable mixed effects logistic regression to assess the association between ICU cohort type and survival. Among ICU admissions in the VPS database, 2010-2018, the prevalence of E-CPR was 0.07%. A total of 671 E-CPR events (650 patients) comprised the final cohort; congenital heart disease (84%) was the most common diagnosis versus acquired heart diseases. The majority of E-CPR events occurred in mixed ICUs (67%, n = 449) and in ICUs with greater than 20 licensed bed capacity (65%, n = 436). Survival to hospital discharge was 51% for the overall cohort. Independent logistic regression failed to reveal any association between survival to hospital discharge and ICU type (ICU type: cardiac ICU, odds ratio [OR], 1.01; 95% CI, 0.71-1.44; p = 0.95). However, multivariable logistic regression revealed an association between cardiac surgical patients and greater odds for survival (OR, 2.03; 95% CI, 1.40-2.95; p < 0.001). Also, there was an association between ICUs with capacity greater than 20 (vs not) and lower survival odds (OR, 0.65; 95% CI, 0.43-0.96). CONCLUSIONS: The overall prevalence of E-CPR among critically ill children with cardiac disease observed in the VPS database is low. We failed to identify an association between ICU cohort type and survival. Further investigation into organizational factors is warranted.

Death and Ultrasound Evidence of the Akinetic Heart in Pediatric Cardiac Arrest.

Point-of-care ultrasound (POCUS) is an expanding noninvasive diagnostic modality used for the management of patients in multiple intensive care and pediatric specialties. POCUS is used to assess cardiac activity and pathology, pulmonary disease, intravascular volume status, intra-abdominal processes, procedural guidance including vascular access, lumbar puncture, thoracentesis, paracentesis, and pericardiocentesis. POCUS has also been used to determine anterograde flow following circulatory arrest when organ donation after circulatory death is being considered. Published guidelines exist from multiple medical societies including the recent guidelines for the use of POCUS in neonatology for diagnostic and procedural purposes.

A survey of current practices in sedation, analgesia, withdrawal, and delirium management in paediatric cardiac ICUs.

OBJECTIVE: To characterise the current approach to sedation, analgesia, iatrogenic withdrawal syndrome and delirium in paediatric cardiac ICUs. DESIGN: A convenience sample survey of practitioners at institutions participating in the Pediatric Cardiac Critical Care Consortium conducted from September to December 2020. SETTING: Paediatric cardiac ICUs. MEASUREMENTS AND MAIN RESULTS: Survey responses were received from 33 of 42 institutions contacted. Screening for pain and agitation occurs commonly and frequently. A minority of responding centres (39%) have a written analgesia management protocol/guideline. A minority (42%) of centres have a written protocol for sedation. Screening for withdrawal occurs commonly, although triggers for withdrawal screening vary. Only 42% of respondents have written protocols for withdrawal management. Screening for delirium occurs "always" in 46% of responding centres, "sometimes" in 36% of centres and "never" 18%. Nine participating centres (27%) have written protocols for delirium management. CONCLUSIONS: Our survey identified that most responding paediatric cardiac ICUs lack a standardised approach to the management of analgesia, sedation, iatrogenic withdrawal, and delirium. Screening for pain and agitation occurs regularly, while screening for withdrawal occurs fairly frequently, and screening for delirium is notably less consistent. Only a minority of centres use written protocols or guidelines for the management of these problems. We believe that this represents an opportunity to significantly improve patient care within the paediatric cardiac ICU.

Circulating miR-206 and miR-1246 as Markers in the Early Diagnosis of Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

Lung cancer (LC) is the most common cause of cancer death, with 75% of cases being diagnosed in late stages. This study aimed to determine potential miRNAs as biomarkers for the early detection of LC in chronic obstructive pulmonary disease (COPD) cases. Ninety-nine patients were included, with registered clinical and lung function parameters followed for 6 years. miRNAs were determined in 16 serum samples from COPD patients (four with LC and four controls) by next generation sequencing (NGS) at LC diagnosis and 3 years before. The validation by qPCR was performed in 33 COPD-LC patients and 66 controls at the two time points. Over 170 miRNAs (≥10 TPM) were identified; among these, miR-224-5p, miR-206, miR-194-5p, and miR-1246 were significantly dysregulated (p < 0.001) in COPD-LC 3 years before LC diagnosis when compared to the controls. The validation showed that miR-1246 and miR-206 were differentially expressed in COPD patients who developed LC three years before (p = 0.035 and p = 0.028, respectively). The in silico enrichment analysis showed miR-1246 and miR-206 to be linked to gene mediators in various signaling pathways related to cancer. Our study demonstrated that miR-1246 and miR-206 have potential value as non-invasive biomarkers of early LC detection in COPD patients who could benefit from screening programs.

Pulmonary Paragonimiasis in Native Community, Esmeraldas Province, Ecuador, 2022.

Paragonimiasis is a food-borne infection caused by several species of the Paragonimus fluke. Clinical manifestations can mimic tuberculosis and contribute to diagnostic delay. We report a cluster of paragonimiasis in a community in Ecuador, where active surveillance was set up after detection of the first 2 cases.

PaIntDB: network-based omics integration and visualization using protein-protein interactions in Pseudomonas aeruginosa.

SUMMARY: The Pseudomonas aeruginosa Interaction Database, PaIntDB, is an intuitive web-based tool for network-based systems biology analyses using protein-protein interactions (PPI) in this medically important pathogen. It enables the integration and visualization of omics analyses including RNA-Seq and Tn-Seq. High-throughput datasets can be mapped onto PPI networks, which can be explored visually and filtered to uncover novel putative molecular pathways related to the conditions of study. PaIntDB contains the most comprehensive P.aeruginosa interactome to date, collected from a variety of resources, including interactions predicted computationally to further expand analysis capabilities. The web server implementation makes it easily extendable to other bacterial species. AVAILABILITY AND IMPLEMENTATION: PaIntDB is freely available at https://www.paintdb.ca, the source code and database file are available at https://github.com/yavyx/PaIntDB. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Neural network features distinguish chemosensory stimuli in Caenorhabditis elegans.

Nervous systems extract and process information from the environment to alter animal behavior and physiology. Despite progress in understanding how different stimuli are represented by changes in neuronal activity, less is known about how they affect broader neural network properties. We developed a framework for using graph-theoretic features of neural network activity to predict ecologically relevant stimulus properties, in particular stimulus identity. We used the transparent nematode, Caenorhabditis elegans, with its small nervous system to define neural network features associated with various chemosensory stimuli. We first immobilized animals using a microfluidic device and exposed their noses to chemical stimuli while monitoring changes in neural activity of more than 50 neurons in the head region. We found that graph-theoretic features, which capture patterns of interactions between neurons, are modulated by stimulus identity. Further, we show that a simple machine learning classifier trained using graph-theoretic features alone, or in combination with neural activity features, can accurately predict salt stimulus. Moreover, by focusing on putative causal interactions between neurons, the graph-theoretic features were almost twice as predictive as the neural activity features. These results reveal that stimulus identity modulates the broad, network-level organization of the nervous system, and that graph theory can be used to characterize these changes.

Nucleus Accumbens Stimulation Modulates Inhibitory Control by Right Prefrontal Cortex Activation in Obsessive-Compulsive Disorder.

Inhibitory control is considered a compromised cognitive function in obsessive-compulsive (OCD) patients and likely linked to corticostriatal circuitry disturbances. Here, 9 refractory OCD patients treated with deep brain stimulation (DBS) were evaluated to address the dynamic modulations of large-scale cortical network activity involved in inhibitory control after nucleus accumbens (NAc) stimulation and their relationship with cortical thickness. A comparison of DBS "On/Off" states showed that patients committed fewer errors and exhibited increased intraindividual reaction time variability, resulting in improved goal maintenance abilities and proactive inhibitory control. Visual P3 event-related potentials showed increased amplitudes during Go/NoGo performance. Go and NoGo responses increased cortical activation mainly over the right inferior frontal gyrus and medial frontal gyrus, respectively. Moreover, increased cortical activation in these areas was equally associated with a higher cortical thickness within the prefrontal cortex. These results highlight the critical role of NAc DBS for preferentially modulating the neuronal activity underlying sustained speed responses and inhibitory control in OCD patients and show that it is triggered by reorganizing brain functions to the right prefrontal regions, which may depend on the underlying cortical thinning. Our findings provide updated structural and functional evidence that supports critical dopaminergic-mediated frontal-striatal network interactions in OCD.