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Burns : Journal of the International... Jun 2024Acute kidney injury (AKI) is a common complication of severe burn injury and is associated with significant morbidity and mortality. Continuous Renal Replacement Therapy...
Acute kidney injury (AKI) is a common complication of severe burn injury and is associated with significant morbidity and mortality. Continuous Renal Replacement Therapy (CRRT) is the preferred treatment for stage 3 AKI due to severe burn. This retrospective cohort study at a single institution aimed to examine the long-term renal outcomes after discharge of burn survivors who underwent CRRT during their ICU stay between 2012-2021 due to burn-related AKI, hypothesizing a return to baseline renal function in the long term. Among the 31 patients meeting inclusion criteria, 22 survived their burn injuries, resulting in a 29 % mortality rate. No significant disparities were observed in demographics, comorbidities, burn characteristics, or critical care interventions between survivors and non-survivors. Serum creatinine and eGFR values normalized for 91 % of patients at discharge. Impressively, 91 % of survivors demonstrated a return to baseline renal function during long-term (>3 years) follow-up. Furthermore, only 18 % underwent dialysis after discharge, primarily within the first year. Cumulative mortality rates were 18.2 %, 22.7 %, and 31.8 % at 1, 3, and > 3 years after discharge, respectively. Causes of death were primarily non-renal. These results suggest that burn-related AKI with CRRT results in lower rates of conversion to ongoing renal dysfunction compared to general ICU cohorts. Despite limitations, this study contributes vital insights into the underexplored issue of long-term outcomes after dicharge in this patient population.
PubMed: 38862345
DOI: 10.1016/j.burns.2024.05.019 -
Pharmacological Research Jul 2024Research has shown that a significant portion of cancer patients experience depressive symptoms, often accompanied by neuroendocrine hormone imbalances. Depression is... (Review)
Review
Research has shown that a significant portion of cancer patients experience depressive symptoms, often accompanied by neuroendocrine hormone imbalances. Depression is frequently associated with decreased levels of serotonin with the alternate name 5-hydroxytryptamine (5-HT), leading to the common use of selective serotonin reuptake inhibitors (SSRIs) as antidepressants. However, the role of serotonin in tumor regulation remains unclear, with its expression levels displaying varied effects across different types of tumors. Tumor initiation and progression are closely intertwined with the immune function of the human body. Neuroimmunity, as an interdisciplinary subject, has played a unique role in the study of the relationship between psychosocial factors and tumors and their mechanisms in recent years. This article offers a comprehensive review of serotonin's regulatory roles in tumor onset and progression, as well as its impacts on immune cells in the tumor microenvironment. The aim is to stimulate further interdisciplinary research and discover novel targets for tumor treatment.
Topics: Humans; Neoplasms; Serotonin; Animals; Tumor Microenvironment
PubMed: 38862071
DOI: 10.1016/j.phrs.2024.107255 -
Journal of Clinical & Translational... Jun 2024To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D.
OBJECTIVES
To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D.
RESEARCH DESIGN AND METHODS
Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team.
RESULTS
Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event.
CONCLUSIONS
The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034.
PubMed: 38860154
DOI: 10.1016/j.jcte.2024.100352 -
The Journal of Headache and Pain Jun 2024Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients.
METHODS
The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes.
RESULTS
177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02).
CONCLUSIONS
Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients.
TRIAL REGISTRATION
Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018.
Topics: Humans; Mindfulness; Headache Disorders, Secondary; Female; Male; Adult; Middle Aged; Longitudinal Studies; Single-Blind Method; Magnetic Resonance Imaging; Default Mode Network; Cerebral Cortex
PubMed: 38858629
DOI: 10.1186/s10194-024-01803-5 -
BMJ Open Jun 2024In the face of unprecedented demand, the Welsh Ambulance Services University NHS Trust developed 'Blue Light Hub': a new app to educate primary school-aged children...
"When you're hurt and you need serious help you call 999." Educating children about emergency services and appropriate use of 999: An evaluation study of the Blue Light Hub app.
OBJECTIVES
In the face of unprecedented demand, the Welsh Ambulance Services University NHS Trust developed 'Blue Light Hub': a new app to educate primary school-aged children about emergency services. Our overarching aim was to examine the effectiveness of the app.
DESIGN
Primary school-aged children from three schools in South Wales, UK, played with the app for 2 hours over 2 weeks in class time. Children completed quizzes to assess their knowledge and awareness of, and confidence in engaging with, emergency services before and after using the app.
PARTICIPANTS
Our evaluation focused on N=393 children who completed both the pre-test and post-test quizzes. On average, children were 8-9 years old (median school year, Year 4); 47.8% were male and 50.9% were female.
RESULTS
After using the app, there was a significant increase in the proportion of children who knew of appropriate actions to take in non-emergency scenarios, χ(1) = 26.01, and could provide a question a call handler would ask them if they called 999, χ(1) = 13.79. There was also an increase in the proportion of children who could identify an National Health Service (NHS) service that could help them if they were unwell, χ(1) = 33.31, name different roles in the NHS, χ(1) = 12.80 and knew how dialling 111 could help them χ(1) = 90.05 (all p values<0.001).
CONCLUSION
To our knowledge, Blue Light Hub is the first app of its kind designed to educate primary school-aged children about emergency services. Our findings provide preliminary evidence that the app supports children's knowledge and awareness of emergency services.
Topics: Humans; Child; Female; Male; Mobile Applications; Wales; Emergency Medical Services; Health Knowledge, Attitudes, Practice; Health Education; Ambulances; Blue Light
PubMed: 38858135
DOI: 10.1136/bmjopen-2023-079214 -
Asian Journal of Surgery Jun 2024
PubMed: 38853115
DOI: 10.1016/j.asjsur.2024.05.209 -
PloS One 2024Neuroimaging studies have shown that activity in the prefrontal cortex correlates with two critical aspects of normal memory functioning: retrieval of episodic memories...
Neuroimaging studies have shown that activity in the prefrontal cortex correlates with two critical aspects of normal memory functioning: retrieval of episodic memories and subjective "feelings-of-knowing" about our memory. Brain stimulation can be used to test the causal role of the prefrontal cortex in these processes, and whether the role differs for the left versus right prefrontal cortex. We compared the effects of online High-Definition transcranial Direct Current Stimulation (HD-tDCS) over the left or right dorsolateral prefrontal cortex (DLPFC) compared to sham during a proverb-name associative memory and feeling-of-knowing task. There were no significant effects of HD-tDCS on either associative recognition or feeling-of-knowing performance, with Bayesian analyses showing moderate support for the null hypotheses. Despite past work showing effects of HD-tDCS on other memory and feeling-of-knowing tasks, and neuroimaging showing effects with similar tasks, these findings add to the literature of non-significant effects with tDCS. This work highlights the need to better understand factors that determine the effectiveness of tDCS, especially if tDCS is to have a successful future as a clinical intervention.
Topics: Humans; Transcranial Direct Current Stimulation; Male; Female; Adult; Young Adult; Dorsolateral Prefrontal Cortex; Memory; Bayes Theorem; Adolescent; Prefrontal Cortex
PubMed: 38848375
DOI: 10.1371/journal.pone.0300779 -
Journal of Cellular and Molecular... Jun 2024Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by pulmonary and systemic congestion resulting from left ventricular...
Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by pulmonary and systemic congestion resulting from left ventricular diastolic dysfunction and increased filling pressure. Currently, however, there is no evidence on effective pharmacotherapy for HFpEF. In this study, we aimed to investigate the therapeutic effect of total xanthones extracted from Gentianella acuta (TXG) on HFpEF by establishing an high-fat diet (HFD) + L-NAME-induced mouse model. Echocardiography was employed to assess the impact of TXG on the cardiac function in HFpEF mice. Haematoxylin and eosin staining, wheat germ agglutinin staining, and Masson's trichrome staining were utilized to observe the histopathological changes following TXG treatment. The results demonstrated that TXG alleviated HFpEF by reducing the expressions of genes associated with myocardial hypertrophy, fibrosis and apoptosis. Furthermore, TXG improved cardiomyocyte apoptosis by inhibiting the expression of apoptosis-related proteins. Mechanistic investigations revealed that TXG could activate the inositol-requiring enzyme 1α (IRE1α)/X-box-binding protein 1 (Xbp1s) signalling pathway, but the knockdown of IRE1α using the IRE1α inhibitor STF083010 or siRNA-IRE1α impaired the ability of TXG to ameliorate cardiac remodelling in HFpEF models. In conclusion, TXG alleviates myocardial hypertrophy, fibrosis and apoptosis through the activation of the IRE1α/Xbp1s signalling pathway, suggesting its potential beneficial effects on HFpEF patients.
Topics: Animals; Endoribonucleases; Heart Failure; X-Box Binding Protein 1; Protein Serine-Threonine Kinases; Signal Transduction; Mice; Male; Xanthones; Apoptosis; Disease Models, Animal; Mice, Inbred C57BL; Myocytes, Cardiac; Diet, High-Fat; Fibrosis; Stroke Volume
PubMed: 38847482
DOI: 10.1111/jcmm.18466 -
Journal of Hematology & Oncology Jun 2024Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the...
Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p < 0.001). The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p < 0.0001) for the non-EMD cohort. In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.5 (1.1-2.2), p = 0.02]. The median overall survival was 14.8 months [95% CI: 9-Not reached (NR)] vs. 26.9 months (26.3 vs. NR, p = 0.006) for the EMD and non-EMD cohorts, respectively. Extramedullary disease represents an independent predictor of inferior day 90 ORR and PFS among patients treated with ide-cel.
Topics: Humans; Multiple Myeloma; Male; Female; Middle Aged; Aged; Adult; Aged, 80 and over; Tissue Extracts; Treatment Outcome; Biological Products; Retrospective Studies; Immunotherapy, Adoptive; Progression-Free Survival; Receptors, Chimeric Antigen
PubMed: 38845015
DOI: 10.1186/s13045-024-01555-4 -
Scientific Reports Jun 2024Sleep onset insomnia is a pervasive problem that contributes significantly to the poor health outcomes associated with insufficient sleep. Auditory stimuli phase-locked... (Randomized Controlled Trial)
Randomized Controlled Trial
Sleep onset insomnia is a pervasive problem that contributes significantly to the poor health outcomes associated with insufficient sleep. Auditory stimuli phase-locked to slow-wave sleep oscillations have been shown to augment deep sleep, but it is unknown whether a similar approach can be used to accelerate sleep onset. The present randomized controlled crossover trial enrolled adults with objectively verified sleep onset latencies (SOLs) greater than 30 min to test the effect of auditory stimuli delivered at specific phases of participants' alpha oscillations prior to sleep onset. During the intervention week, participants wore an electroencephalogram (EEG)-enabled headband that delivered acoustic pulses timed to arrive anti-phase with alpha for 30 min (Stimulation). During the Sham week, the headband silently recorded EEG. The primary outcome was SOL determined by blinded scoring of EEG records. For the 21 subjects included in the analyses, stimulation had a significant effect on SOL according to a linear mixed effects model (p = 0.0019), and weekly average SOL decreased by 10.5 ± 15.9 min (29.3 ± 44.4%). These data suggest that phase-locked acoustic stimulation can be a viable alternative to pharmaceuticals to accelerate sleep onset in individuals with prolonged sleep onset latencies. Trial Registration: This trial was first registered on clinicaltrials.gov on 24/02/2023 under the name Sounds Locked to ElectroEncephalogram Phase For the Acceleration of Sleep Onset Time (SLEEPFAST), and assigned registry number NCT05743114.
Topics: Humans; Male; Female; Adult; Sleep Initiation and Maintenance Disorders; Acoustic Stimulation; Middle Aged; Electroencephalography; Cross-Over Studies; Treatment Outcome; Alpha Rhythm
PubMed: 38844793
DOI: 10.1038/s41598-024-63385-1