Noninvasive Ventilation for Preoxygenation during Emergency Intubation.

BACKGROUND: Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain. METHODS: In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. RESULTS: Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.).

Machine Learning Predicts Unplanned Care Escalations for Post-Anesthesia Care Unit Patients during the Perioperative Period: A Single-Center Retrospective Study.

BACKGROUND:  Despite low mortality for elective procedures in the United States and developed countries, some patients have unexpected care escalations (UCE) following post-anesthesia care unit (PACU) discharge. Studies indicate patient risk factors for UCE, but determining which factors are most important is unclear. Machine learning (ML) can predict clinical events. We hypothesized that ML could predict patient UCE after PACU discharge in surgical patients and identify specific risk factors. METHODS: We conducted a single center, retrospective analysis of all patients undergoing non-cardiac surgery (elective and emergent). We collected data from pre-operative visits, intra-operative records, PACU admissions, and the rate of UCE. We trained a ML model with this data and tested the model on an independent data set to determine its efficacy. Finally, we evaluated the individual patient and clinical factors most likely to predict UCE risk. RESULTS: Our study revealed that ML could predict UCE risk which was approximately 5% in both the training and testing groups. We were able to identify patient risk factors such as patient vital signs, emergent procedure, ASA Status, and non-surgical anesthesia time as significant variable. We plotted Shapley values for significant variables for each patient to help determine which of these variables had the greatest effect on UCE risk. Of note, the UCE risk factors identified frequently by ML were in alignment with anesthesiologist clinical practice and the current literature. CONCLUSIONS: We used ML to analyze data from a single-center, retrospective cohort of non-cardiac surgical patients, some of whom had an UCE. ML assigned risk prediction for patients to have UCE and determined perioperative factors associated with increased risk. We advocate to use ML to augment anesthesiologist clinical decision-making, help decide proper disposition from the PACU, and ensure the safest possible care of our patients.

Spatio-temporal trends in livestock exposure to per- and polyfluoroalkyl substances (PFAS) inform risk assessment and management measures.

The migration of per- and polyfluoroalkyl substances (PFAS) onto agricultural properties has resulted in the accumulation of PFAS in livestock. The environmental determinants of PFAS accumulation in livestock from the grazing environment are poorly understood, resulting in limited capacity to manage livestock exposure and subsequent transfer of PFAS through the food chain. Analytical- (n = 978 samples of soil, water, pasture, and serum matrices), farm management/practice- and livestock physiology data were collated and interrogated from environmental PFAS investigations across ten farms, from four agro-ecological regions of Victoria (Australia). Statistical analysis identified perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) as key analytes of concern for livestock bioaccumulation. PFOS and PFHxS concentrations in livestock drinking water were positively correlated with serum concentrations while other intake pathways (pasture and soil) had weaker correlations. Seasonal trends in PFAS body burden (serum concentrations) were identified and suggested to be linked to seasonal grazing behaviours and physiological water requirements. The data showed for the first time that livestock exposure to PFAS is dynamic and with relatively short elimination half-lives, there is opportunity for exposure management. Meat from cattle, grazed on PFAS impacted sites, may exceed health-based guideline values for PFAS, especially for markets with low limits (like the European Commission Maximum Limits or EC MLs). This study found that sites with mean livestock drinking water concentrations as low as 0.003 µg PFOS/L may exceed the EC ML for PFOS in cattle meat. Risk assessment can be used to prioritise site cleanup and development of management plans to reduce PFAS body burden by considering timing of stock rotation and/or supplementation of primary exposure sources.

Proceedings of the 2022 UAB CRRT Academy: Non-Invasive Hemodynamic Monitoring to Guide Fluid Removal with CRRT and Proliferation of Extracorporeal Blood Purification Devices.

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.

Proton-Induced Spin State Switching in an FeIII Complex.

Reversible proton-induced spin state switching of an FeIII complex in solution is observed at room temperature. A reversible magnetic response was detected in the complex, [FeIII (sal2 323)]ClO4 (1), using Evans' method 1 H NMR spectroscopy which indicated cumulative switching from low-spin to high-spin upon addition of one and two equivalents of acid. Infrared spectroscopy suggests a coordination-induced spin state switching (CISSS) effect, whereby protonation displaces the metal-phenoxo donors. The analogous complex, [FeIII (4-NEt2 -sal2 323)]ClO4 (2), with a diethylamino group on the ligand, was used to combine the magnetic change with a colorimetric response. Comparison of the protonation responses of 1 and 2 reveals that the magnetic switching is caused by perturbation of the immediate coordination sphere of the complex. These complexes constitute a new class of analyte sensor which operate by magneto-modulation, and in the case of 2, also yield a colorimetric response.

Online Interactive Platform for COVID-19 Literature Visual Analytics: Platform Development Study.

BACKGROUND: Papers on COVID-19 are being published at a high rate and concern many different topics. Innovative tools are needed to aid researchers to find patterns in this vast amount of literature to identify subsets of interest in an automated fashion. OBJECTIVE: We present a new online software resource with a friendly user interface that allows users to query and interact with visual representations of relationships between publications. METHODS: We publicly released an application called PLATIPUS (Publication Literature Analysis and Text Interaction Platform for User Studies) that allows researchers to interact with literature supplied by COVIDScholar via a visual analytics platform. This tool contains standard filtering capabilities based on authors, journals, high-level categories, and various research-specific details via natural language processing and dozens of customizable visualizations that dynamically update from a researcher's query. RESULTS: PLATIPUS is available online and currently links to over 100,000 publications and is still growing. This application has the potential to transform how COVID-19 researchers use public literature to enable their research. CONCLUSIONS: The PLATIPUS application provides the end user with a variety of ways to search, filter, and visualize over 100,00 COVID-19 publications.

Torsion of a Wandering Spleen Managed Conservatively: Rare and Interesting.

Wandering spleen is a rare pathology. A 2-year-old child with abdominal pain was diagnosed to have a torted, avascular wandering spleen. On conservative management, she remains well with no radiological evidence of the spleen. Splenic torsion usually warrants surgery. Nonoperative management in selected cases allows the natural process of autosplenectomy.

Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin-Angiotensin-Aldosterone System Inhibitors.

OBJECTIVES: To compare the hemodynamic response in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy with those who were not. DESIGN: Single-center, retrospective cohort study. SETTING: Medical and surgical ICUs at a 1,100-bed academic medical center. PATIENTS: Medical and surgical ICU patients with septic shock who received vasopressin infusion added to at least one concomitant vasopressor agent between January 2014 and December 2015, then divided into two cohorts: 1) patients who were on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients and 2) patients who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy as outpatients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure at 6 hours was 72.2 mm Hg in the renin-angiotensin-aldosterone system inhibitor group versus 69.7 mm Hg in the non-renin-angiotensin-aldosterone system inhibitor group (p = 0.298). There was no difference in mean arterial pressure at 1, 24, or 48 hours between groups. Total concomitant vasopressor requirements, based on norepinephrine equivalents excluding vasopressin, were significantly lower at 24 hours in the renin-angiotensin-aldosterone system inhibitor group versus the non-renin-angiotensin-aldosterone system inhibitor group (10.7 vs 18.1 µg/min, respectively; p = 0.007), but no significant differences were seen at the other time points assessed. There were no significant differences in ICU or hospital length of stay or mortality. CONCLUSIONS: There was no significant difference in the primary outcome of 6-hour mean arterial pressure in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy versus those receiving vasopressin who were not on chronic renin-angiotensin-aldosterone system inhibitor therapy. Renin-angiotensin-aldosterone system inhibitor patients had lower total concomitant vasopressor requirements at 24 hours compared with non-renin-angiotensin-aldosterone system inhibitor patients.

Shunt tube placement for amelioration of cerebrospinal fluid flow obstruction caused by spinal cord subarachnoid fibrosis in dogs.

OBJECTIVE: To describe a novel technique for ameliorating cerebrospinal fluid flow obstruction secondary to pia-arachnoid fibrosis in dogs and report outcome. STUDY DESIGN: Descriptive report and retrospective case series. ANIMALS: Dogs with cerebrospinal fluid (CSF) flow obstruction (n = 7). METHODS: Medical records were searched for dogs that had a subarachnoid-subarachnoid shunt placed for treatment of CSF flow obstruction. Data collected included age, sex, breed, clinical signs and duration of signs prior to examination, neurologic status and localization prior to surgery, pre-surgical diagnostics, surgical technique, histopathology, postoperative neurologic examination, time to discharge from hospital, and outcome. RESULTS: All dogs were diagnosed at surgery with a fibrotic adhesion between the arachnoid and pia mater. A subarachnoid shunting tube was implanted to allow CSF flow across the lesion site. Five dogs showed improvement of clinical signs, 3 of which showed complete recovery and 2 of which showed improvement without resolution of all clinical signs. Two dogs showed no change at 7 and 24 months postoperatively. CONCLUSION: Bridging a region of pia-arachnoid fibrosis with a tube placed in the subarachnoid space can ameliorate or prevent progression of associated clinical signs.

Epidural insertion height for ureteric reimplant surgery; does location matter?

BACKGROUND: Surgical correction of vesicoureteric reflux through ureteric reimplantation is a common, highly successful treatment. Postoperative pain can be severe and may relate to somatic wound pain from the lower abdominal incision or from visceral bladder spasm pain. AIM: To conduct a prospective quality improvement audit to compare four perioperative analgesic techniques. METHODS: Observational data were collected on 217 patients following open ureteroneocystostomy over 5 days. The patients were split into four groups: (i) 'morphine' infusion; (ii) 'caudal'-single-shot caudal; (iii) 'epidural'-epidural catheter inserted at T10-L2 given a bolus, followed by an infusion of 0.125% bupivacaine with fentanyl 2 µg·ml(-1) ; (iv) 'caudal catheter'-caudal placed epidural catheter was treated similar to the epidural catheter. Data regarding postoperative analgesic interventions were recorded. Intravesical pethidine was used for bladder spasm pain and i.v. morphine for wound pain. RESULTS: Over the study period, the caudal catheter technique (mean interventions/patient = 1.8 ± 2.6) and the single-shot caudal (6.1 ± 4) needed significantly less bladder spasm interventions than morphine (9.2 ± 4) and epidural (8.0 ± 4.4) patients. For wound pain, the caudal catheter (8.8 ± 3.3) and epidural groups (11.4 ± 3.2) needed significantly less interventions than morphine (16.1 ± 3) and caudal (15.3 ± 3.3) patients. Overall, caudal catheter patients on average required about half the number of pain interventions and were associated with less high nursing workload. CONCLUSIONS: Despite some limitations in data collection and study design, the caudal catheter technique was superior at reducing pain interventions, particularly bladder spasm interventions. Overall epidural analgesia was not superior to a single-shot caudal followed by opioid infusion. The issue of bladder spasm may be similar to the phenomenon of sacral sparing in obstetric epidural anesthesia. Thus, regional techniques, such as caudal epidural, targeting a better balance between sacral and lumber nerves are required.

RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators.

The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. There is increasing evidence for important functional interactions between the miRNA and nuclear receptor (NR) signaling networks, with recent data showing that estrogen, acting through the estrogen receptor, can modulate initial aspects of nuclear miRNA processing. Here, we show that the cytoplasmic RISC proteins PACT, TRBP, and Dicer are steroid receptor RNA activator (SRA) binding NR coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression. Furthermore, each of the RISC proteins, together with Argonaute 2, associates with SRA and specific pre-microRNAs in both the nucleus and cytoplasm, providing evidence for links between NR-mediated transcription and some of the factors involved in miRNA processing.

Suspected primary hematomyelia in 3 dogs.

Primary hematomyelia refers to hemorrhage occurring within the spinal cord without an identifiable etiology. Clinical signs, magnetic resonance imaging characteristics, and histopathological findings are described. Diagnosis was made through histological analysis and rule-outs for underlying factors. Following removal of the hematoma, neurologic deficits improved, although some residual deficits persisted.

Hématomyélie primaire suspectée chez 3 chiens. L'hématomyélie primaire fait référence à l'hémorragie qui se produit dans la moelle épinière sans une étiologie identifiable. Les signes cliniques, les caractéristiques de l'imagerie par résonance magnétique et les résultats de l'histopathologie sont décrits. Le diagnostic a été posé à l'aide d'une analyse histologique et de l'élimination des facteurs sous-jacents. Après l'enlèvement de l'hématome, le déficit neurologique s'est amélioré, même si des déficits résiduels ont persisté.(Traduit par Isabelle Vallières).

Contribution of the first K-homology domain of poly(C)-binding protein 1 to its affinity and specificity for C-rich oligonucleotides.

Poly-C-binding proteins are triple KH (hnRNP K homology) domain proteins with specificity for single stranded C-rich RNA and DNA. They play diverse roles in the regulation of protein expression at both transcriptional and translational levels. Here, we analyse the contributions of individual αCP1 KH domains to binding C-rich oligonucleotides using biophysical and structural methods. Using surface plasmon resonance (SPR), we demonstrate that KH1 makes the most stable interactions with both RNA and DNA, KH3 binds with intermediate affinity and KH2 only interacts detectibly with DNA. The crystal structure of KH1 bound to a 5'-CCCTCCCT-3' DNA sequence shows a 2:1 protein:DNA stoichiometry and demonstrates a molecular arrangement of KH domains bound to immediately adjacent oligonucleotide target sites. SPR experiments, with a series of poly-C-sequences reveals that cytosine is preferred at all four positions in the oligonucleotide binding cleft and that a C-tetrad binds KH1 with 10 times higher affinity than a C-triplet. The basis for this high affinity interaction is finally detailed with the structure determination of a KH1.W.C54S mutant bound to 5'-ACCCCA-3' DNA sequence. Together, these data establish the lead role of KH1 in oligonucleotide binding by αCP1 and reveal the molecular basis of its specificity for a C-rich tetrad.

Management of duplex-system ureterocele.

AIM: To analyse different treatment modalities, functional outcome and continence in children treated for duplex-system ureterocele and to review the relevant literature. METHODS: The medical records of patients with duplex-system ureterocele treated between 2001 and 2011 were reviewed retrospectively. RESULTS: Twenty-two cases were identified. Five patients underwent incision of the ureterocele as initial procedure. It was curative in only one patient. Seven patients underwent upper-pole nephroureterectomy. It was curative in 4 cases. Five patients underwent excision of ureterocele and common-sheath reimplant, and the remaining 5 patients had upper-pole nephroureterectomy and simultaneous excision of ureterocele with lower-moiety ureteric reimplantation. These surgeries were curative in all patients. Follow-up ranged from 4 to 84 months. Functional outcome was good in all patients. Fourteen patients were continent at follow-up, and continence was not assessed in the other 8 because of young age. CONCLUSIONS: Our data suggest a higher rate of secondary procedures if there is retained ureterocele. Data also suggest that complete reconstruction can be safely performed in a young infant without any adverse effect on continence.

Boys with bladder dysfunction may have posterior urethral valves - A simple framework to aid investigation.

BACKGROUND: Bladder dysfunction (BD) is a common presenting complaint to paediatric urology outpatient clinics, accounting for up to 47% of referrals and affecting one in ten children of toilet training age. Boys with bladder dysfunction have been shown to have higher rates of posterior urethral valves (PUV) however when to consider cystourethroscopy in this group is unclear. OBJECTIVE: Our primary aim was to assess the likelihood of detecting PUV in a cohort of boys of toilet training age presenting to a paediatric urologist with symptoms of bladder dysfunction. Our secondary aim was to assess whether resection of PUV was associated with improved clinical outcome. STUDY DESIGN: Retrospective review of male patients aged 4-16 (January 2007 to December 2023), referred to paediatric urologist in an Australian outpatient clinic with BD undergoing cystourethroscopy. Those with known renal tract or spinal pathology were excluded. Patients were divided into four groups according to their symptoms/investigation results. Patients were followed up to assess improvement in symptoms following resection of PUV. RESULTS: 247 boys were included in this study with a median age of 8.1 years. 81/247 (32.8%) had PUV on cystourethroscopy. The highest incidence of PUV 13/25 (52%) was in those patients with BD, haematuria or UTI and ultrasound (USS) changes. There was no difference in outcome improvement in those who underwent resection of PUV when compared with those without PUV. DISCUSSION: Our study findings concur with results from previous literature identifying higher rates of PUV in older boys with bladder dysfunction. We have utilised straightforward clinical criteria to provide a targeted framework for screening with cystourethroscopy. There was no difference in outcomes when PUV was resected, compared to those without PUV. Limitations of this study include the retrospective nature, possible selection and reporting biases. CONCLUSION: The likelihood of detecting PUV in our cohort of boys aged 4-16 with bladder dysfunction was 32.8%. The four groups provide clinicians with guidance on who may benefit from cystoscopy. This study provides future scope for a prospective interventional study of PUV in boys with BD.

Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells.

The enzyme deoxyhypusine hydroxylase (DOHH) catalyzes the activation of eukaryotic translation initiation factor (eIF5A), a protein essential for cell growth. Using bioinformatic predictions and reporter gene assays, we have identified a 182-nt element within the DOHH 3'-untranslated region (3'-UTR) that contains a number of target sites for miR-331-3p and miR-642-5p. Quantitative RT-PCR studies demonstrated overexpression of DOHH mRNA and underexpression of miR-331-3p and miR-642-5p in several prostate cancer cell lines compared with normal prostate epithelial cells. Transient overexpression of miR-331-3p and/or miR-642-5p in DU145 prostate cancer cells reduced DOHH mRNA and protein expression and inhibited cell proliferation. We observed synergistic growth inhibition with the combination of miR-331-3p and miR-642-5p and mimosine, a pharmacological DOHH inhibitor. Finally, we identified a significant inverse relationship between the expression of miR-331-3p or miR-642-5p and DOHH in a cohort of human prostate cancer tissues. Our results suggest a novel role for miR-331-3p and miR-642-5p in the control of prostate cancer cell growth via the regulation of DOHH expression and eIF5A activity.

Altered response to Toll-like receptor 4 activation in fibromyalgia: A low-dose, human experimental endotoxemia pilot study.

In this pilot study, a human intravenous injection of low-dose endotoxin (lipopolysaccharide, LPS) model was used to test if fibromyalgia is associated with altered immune responses to Toll-like receptor 4 (TLR4) activation. Eight women with moderately-severe fibromyalgia and eight healthy women were administered LPS at 0.1 ng/kg in session one and 0.4 ng/kg in session two. Blood draws were collected hourly to characterize the immune response. The primary analytes of interest, leptin and fractalkine, were assayed via commercial radioimmunoassay and enzyme-linked immunosorbent assay kits, respectively. Exploratory analyses were performed on 20 secreted cytokine assays by multiplex cytokine panels, collected hourly. Exploratory analyses were also performed on testosterone, estrogen, and cortisol levels, collected hourly. Additionally, standard clinical complete blood counts with differential (CBC-D) were collected before LPS administration and at the end of the session. The fibromyalgia group demonstrated enhanced leptin and suppressed fractalkine responses to LPS administration. In the exploratory analyses, the fibromyalgia group showed a lower release of IFN-γ, CXCL10, IL-17A, and IL-12 and higher release of IL-15, TARC, MDC, and eotaxin than the healthy group. The results of this study suggest that fibromyalgia may involve an altered immune response to TLR4 activation.