Articles: function.
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The platypnea orthodeoxia syndrome is a rare clinical entity combining positional dyspnea and arterial oxygen desaturation during the transition to orthostatism, reversible on return to decubitus. The most frequent etiology of this syndrome is the presence of a patent foramen ovale (PFO) responsible for a right-to-left intracardiac shunt, the severity of which results in significant functional disability and a risk of death from hypoxia. ⋯ The platypnea orthodeoxia syndrome associated with a patent foramen ovale often suffers from delayed diagnosis. Advanced age and co-morbidities should not prevent patients from undergoing percutaneous PFO closure, as the clinical benefit is important.
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Fibromyalgia syndrome (FMS) is a debilitating widespread chronic pain condition of unclear pathophysiology. We studied small noncoding RNAs as potential classifiers and mediators of FMS. Blood and keratinocyte microRNAs (miRs) and transfer RNA fragments (tRFs) were profiled by small RNA-sequencing within a comprehensively phenotyped female cohort of 53 patients with FMS vs 34 healthy controls (hCOs) and 15 patients with major depression and chronic physical pain (disease controls). ⋯ In blood, altered small RNAs were linked to immune and RNA processes, whereas in keratinocytes, adhesion and epithelial functions were targeted. Modulated tRFs shared sequence motifs in patients with FMS, which may promote concerted pathway regulation. Our findings show miRs/tRFs as key small RNAs dysregulation in FMS pathophysiology and open new perspectives for FMS diagnostics, symptom monitoring, and clinical management.
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Critical care medicine · Dec 2024
Mastering the Sequential Organ Failure Assessment Score: Critical Choices of Score Statistic, Timing, Imputations, and Competing Risk Handling in Major Trials-A Systematic Review.
The Sequential Organ Failure Assessment (SOFA) score originated as a tool for assessing organ dysfunction in critical illness but has expanded to become an outcome measure in clinical trials. We aimed to assess how the SOFA score was used as the primary or secondary endpoint of major randomized controlled trials (RCTs). ⋯ There is major variability in the choice of summary statistic for SOFA score analysis and assessment timepoints, when using it as outcome measure in RCTs. There was either no information or great variability in the handling of missing values, use of imputation, and accounting for competing risk. The current use of SOFA scores in RCTs lacks sufficient reproducibility and statistical and methodological robustness.
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A well-recognized molecular entity involved in pain-related neuroplasticity is the N-methyl-D-aspartate receptor (NMDAR), which is crucial for developing chronic pain. Likewise, the pannexin 1 (Panx1) channel has been described as necessary for initiating and maintaining neuropathic pain, driving nociceptive signals dependent on spinal NMDAR through several possible mechanisms. Through behavioral, pharmacological, and molecular approaches, our study in male rats has revealed several key findings: (1) neurons located in spinal cord laminae I and II express functional Panx1 channels in both neuropathic and sham rats. ⋯ Notably, while 10Panx successfully alleviates hyperalgesia, it does not alter pSrc expression; and (4) NMDA-stimulated YOPRO-1 uptake in neurons of laminae I-II of spinal cord slices were prevented by the NMDAR antagonist D-AP5, the Src inhibitor PP2 (but not PP3), as well as with the 10Panx and carbenoxolone. Therefore, NMDAR activation in dorsal horn neurons triggers an NMDAR-Src-Panx1 signaling pathway, where Panx1 acts as an enhancing effector in neuropathic pain. This implies that disrupting the NMDAR-Panx1 communication (eg, through Src inhibitors and/or Panx1 blockers) may offer a valuable strategy for managing some forms of chronic pain.
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Randomized Controlled Trial Multicenter Study Comparative Study
Short-term outcomes in infants following general anesthesia with low-dose sevoflurane/dexmedetomidine/remifentanil versus standard dose sevoflurane (The TREX trial).
The Trial Remifentanil DEXmedetomidine (TREX) trial aimed to determine whether, in children less than 2 yr old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia is superior to standard-dose sevoflurane anesthesia in terms of global cognitive function at 3 yr of age. The aim of the current secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms. ⋯ These early postoperative results suggest that in children less than 2 yr of age receiving greater than 2 h of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other.