-
Medicine Nov 2023Severe community-acquired pneumonia (sCAP) is characterized by severe symptoms and a poor prognosis, especially with the recent global impact of novel coronavirus in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe community-acquired pneumonia (sCAP) is characterized by severe symptoms and a poor prognosis, especially with the recent global impact of novel coronavirus in recent years. The use of glucocorticoids in sCAP is currently a subject of debate. To evaluate the clinical efficacy and safety of glucocorticoids and provide guidance for their rational use in clinical practice, we conducted this study.
METHODS
We searched PubMed, Web of Science, and China National Knowledge Infrastructure using the following search terms: "pneumonia", "pneumonias", "Pulmonary Inflammation", "Pulmonary Inflammations", "Lung Inflammation", and "Lung Inflammations". The primary outcomes included mortality and the length of hospital stay. The secondary outcomes included the duration of mechanical ventilation, duration of vasoactive drug use, gastrointestinal bleeding, and multiple infections. The Cochrane Collaboration was used to assess the risk of bias of the included studies. Stata/MP14 was used for meta-analysis.
RESULTS
These studies contained information on 1252 patients who received glucocorticoids and 1280 patients who did not. Meta-analysis showed that there was no difference in terms of mortality [risk ratio (RR) = 0.93, 95% confidence interval (CI): 0.81-1.07, P > .05], gastrointestinal bleeding (RR = 1.38, 95% CI: 0.83-2.30, P < .05), multiple infections (RR = 1.17, 95% CI: 0.90-1.53, P > .05) and length of hospital stay (mean difference [MD] = -0.87, 95% CI: -2.35 to 0.61, P > .05) between the hormonal and nonhormonal groups. However, there was a significant difference in the duration of mechanical ventilation (MD = -1.54; 95% CI, -1.89 to -1.12, P < .05) and the duration of use of vasoactive drugs (MD = -14.09, 95% CI: -15.72 to -12.46, P < .05).
CONCLUSION
Glucocorticoids reduced the duration of mechanical ventilation duration and vasoactive drug use in sCAP patients without increasing the risk of adverse events including hyperglycemia and multiple infections. However, there was no significant difference in mortality or length of hospital stay in sCAP patients between glucocorticoid and non-glucocorticoid groups. Glucocorticoids could be recommended for patients with sCAP with respiratory failure or hemodynamic instability.
Topics: Humans; Glucocorticoids; Randomized Controlled Trials as Topic; Pneumonia; Community-Acquired Infections; Gastrointestinal Hemorrhage; Inflammation
PubMed: 37986401
DOI: 10.1097/MD.0000000000036047 -
Pakistan Journal of Medical Sciences 2024As a common oral health concern, periodontitis has been a source of attention for the global health community because of its linkage with systemic and neurological... (Review)
Review
As a common oral health concern, periodontitis has been a source of attention for the global health community because of its linkage with systemic and neurological diseases. The purpose of the present study is to reveal the mediating role of specific cytokines, neuropeptides, and pathogens in the association of chronic periodontitis and neural disorders. To find the related literature different search engines namely PMC, Science Direct, PubMed, Research Gate, and Google Scholar were explored for a study period of five months from October 2022 to February 2023. This review offers a summary of those neuronal diseases that were more related to human behaviors in association with chronic periodontitis. Those neuronal pathologies mainly included Alzheimer's disease, psychosis, stress, anxiety, dementia, Alzheimer's, major depressive disorder, and diabetic peripheral neuropathy, which may otherwise remain subside or even control in the absence of chronic periodontitis and its mediators. Specifically, periodontitis related specific cytokines i.e. IL-6, IL-1, Tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and alpha1-antichymotrypsin, neuropeptides such as insulin-like growth factor-2 (IGF-2), neuropeptide Y, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP), and a polybacterial pathogenic consortium of porphyromonas gingivalis, tannerella forsythia, and treponema denticola, were involved in the mediation and exacerbation of the associated neuronal cognitive pathologies.
PubMed: 38196480
DOI: 10.12669/pjms.40.1.8097 -
Medicine Oct 2023Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness of intravenous high-dose vitamin C in sepsis and septic shock patients by meta-analysis.
METHODS
The PubMed, Embase, and Cochrane Library electronic databases were searched to identify relevant studies. The primary outcome was defined as the short-term all-cause mortality rate. Secondary outcomes included duration of vasoactive drug use, intensive care unit length of stay, sequential organ failure assessment scores up to 96 hours after treatment and 90-day mortality. Review Manager version 5.4 was used to perform the meta-analysis. Relative risk and mean differences (MD) with 95% confidence intervals were determined using fixed- or random-effects models.
RESULTS
Eight randomized controlled trials (RCTs) comprising 1394 patients were eligible for assessment. Overall, the pooled results showed that high-dose vitamin C decreased short-term all-cause mortality in patients with sepsis, but no significant differences were observed in patients with septic shock. Additionally, high-dose vitamin C was associated with decreased duration of vasoactive drug use in patients with sepsis, but not in patients with septic shock. However, it did not significantly affect the duration of intensive care unit stay in RCTs of patients with sepsis and septic shock. Additionally, it did not significantly affect sequential organ failure assessment scores 96 hours post-treatment or 90-day mortality.
CONCLUSION
These results suggest that intravenous high-dose vitamin C may improve outcomes in patients with sepsis, but do not benefit patients with septic shock. Further RCTs and other studies should be conducted to determine whether vitamin C should be recommended as an adjunctive sepsis treatment.
Topics: Humans; Shock, Septic; Randomized Controlled Trials as Topic; Sepsis; Intensive Care Units; Ascorbic Acid; Antineoplastic Agents
PubMed: 37861551
DOI: 10.1097/MD.0000000000035648 -
The Journal of Infection Sep 2023The optimisation of the use of β-lactam antibiotics (BLA) via prolonged infusions in life-threatening complications such as febrile neutropenia (FN) is still... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimisation of the use of β-lactam antibiotics (BLA) via prolonged infusions in life-threatening complications such as febrile neutropenia (FN) is still controversial. This systematic review and meta-analysis aim to evaluate the efficacy of this strategy in onco-haematological patients with FN.
METHODS
A systematic search was performed of PubMed, Web of Science, Cochrane, EMBASE, World Health Organization, and ClinicalTrials.gov, from database inception until December 2022. The search included randomised controlled trials (RCTs) and observational studies that compared prolonged vs short-term infusions of the same BLA. The primary outcome was all-cause mortality. Secondary outcomes were defervescence, requirement of vasoactive drugs, length of hospital stay and adverse events. Pooled risk ratios were calculated using random effects models.
RESULTS
Five studies were included, comprising 691 episodes of FN, mainly in haematological patients. Prolonged infusion was not associated with a reduction in all-cause mortality (pRR 0.83; 95% confidence interval 0.47-1.48). Nor differences were found in secondary outcomes.
CONCLUSIONS
The limited data available did not show significant differences in terms of all-cause mortality or significant secondary outcomes in patients with FN receiving BLA in prolonged vs. short-term infusion. High-quality RCTs are needed to determine whether there are subgroups of FN patients who would benefit from prolonged BLA infusion.
Topics: Humans; Anti-Bacterial Agents; Monobactams; Febrile Neutropenia
PubMed: 37423503
DOI: 10.1016/j.jinf.2023.06.023 -
BioRxiv : the Preprint Server For... Feb 2024Sensory neurons sense pathogenic infiltration, serving to inform immune coordination of host defense. However, sensory neuron-immune interactions have been predominantly...
Sensory neurons sense pathogenic infiltration, serving to inform immune coordination of host defense. However, sensory neuron-immune interactions have been predominantly shown to drive innate immune responses. Humoral memory, whether protective or destructive, is acquired early in life - as demonstrated by both early exposure to streptococci and allergic disease onset. Our study further defines the role of sensory neuron influence on humoral immunity in the lung. Using a murine model of pre-exposure and infection and a model of allergic asthma, we show that sensory neurons are required for B-cell and plasma cell recruitment and antibody production. In response to , sensory neuron depletion resulted in a larger bacterial burden, reduced B-cell populations, IgG release and neutrophil stimulation. Conversely, sensory neuron depletion reduced B-cell populations, IgE and asthmatic characteristics during allergen-induced airway inflammation. The sensory neuron neuropeptide released within each model differed. With bacterial infection, vasoactive intestinal polypeptide (VIP) was preferentially released, whereas substance P was released in response to asthma. Administration of VIP into sensory neuron-depleted mice suppressed bacterial burden and increased IgG levels, while VIP1R deficiency increased susceptibility to bacterial infection. Sensory neuron-depleted mice treated with substance P increased IgE and asthma, while substance P genetic ablation resulted in blunted IgE, similar to sensory neuron-depleted asthmatic mice. These data demonstrate that the immunogen differentially stimulates sensory neurons to release specific neuropeptides which specifically target B-cells. Targeting sensory neurons may provide an alternate treatment pathway for diseases involved with insufficient and/or aggravated humoral immunity.
PubMed: 38260709
DOI: 10.1101/2024.01.04.574231 -
Frontiers in Microbiology 2024Growing studies show that gut microbiota is closely associated with depression. Acupuncture treatment could regulate the gut microbiota of many diseases. Here, we aim to...
BACKGROUND AND OBJECTIVES
Growing studies show that gut microbiota is closely associated with depression. Acupuncture treatment could regulate the gut microbiota of many diseases. Here, we aim to observe the effect of electroacupuncture (EA) on gut microbiota in rats that showed depressive-like behavior.
MATERIALS AND METHODS
The rats were randomly divided into normal group, chronic unpredictable mild stress model (CUMS) group, CUMS + electroacupuncture (EA) group, and CUMS + sham-electroacupuncture (Sham) group. The CUMS+EA rats were treated with EA stimulation at bilateral Zusanli (ST36) and Tianshu (ST25) acupoints for 2 weeks (0.7 mA, 2/100 Hz, 30 min/day). The rats in the sham EA group were treated with the same conditions without inserting needles and electrical stimulation. Behavioral tests were conducted by forced swimming test (FST), open field test (OFT), and sucrose preference test (SPT) to assess depression-like behavior in rats. The relative abundance of intestinal bacteria in rat feces was detected by 16S rRNA analysis. The expression of calcitonin-gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SST), and adrenocorticotropic hormone (ACTH) in serum was detected by ELISA kit, and VIP, CGRP, and SST in the colon were detected by qRT-PCR and Western blot.
RESULTS
Chronic unpredictable mild stress model rats exhibited depressive-like behaviors and had differential abundance vs. control rats. CUMS significantly decreased the relative abundance of Bifidobacterium and Streptococcus at the genus level, CGRP in plasma ( < 0.05), and significantly increased the intestine propulsion rate, the mRNA and protein expression of VIP, SST, and mRNA in the colon, and ATCH in plasma ( < 0.05). EA rats with microbial profiles were distinct from CUMS rats. EA markedly reduced the depressive-like behaviors, significantly increased the intestine propulsion rate, the relative abundance of Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level, Bifidobacterium and Streptococcus at the genus level, and VIP and CGRP in plasma ( < 0.05), and significantly decreased Firmicutes, the ratio of Firmicutes to Bacteroidetes at the phylum level, ACTH and SST in plasma, and SST mRNA in the colon ( < 0.05).
CONCLUSION
The antidepressant effect of EA at ST36 and ST25 is related to regulating intestinal flora and the neurotransmitter system. Our study suggests that EA contributes to the improvement of depression, and gut microbiota may be one of the mechanisms of EA effect.
PubMed: 38601933
DOI: 10.3389/fmicb.2024.1327630 -
Annals of Intensive Care Aug 2023Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this...
BACKGROUND
Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale.
METHOD
The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year.
RESULTS
The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up.
CONCLUSIONS
We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.
PubMed: 37552372
DOI: 10.1186/s13613-023-01164-3 -
Postepy Dermatologii I Alergologii Aug 2023Asthma is a pulmonary disease and its pathogenesis is involved with immune cells and related signalling pathways. Alpha-alumina is material for therapy applications and...
INTRODUCTION
Asthma is a pulmonary disease and its pathogenesis is involved with immune cells and related signalling pathways. Alpha-alumina is material for therapy applications and mucus adhesion promoting protein is cell-surface protein. Vasoactive intestinal peptide (VIP) exerts immunomodulation. Therefore, the drug delivery system and target binding molecule could be applicable for treatment of asthma.
MATERIAL AND METHODS
VIP-MapA-α-alumina was administered to asthmatic mice. Then, eosinophil percentage, IgE, IL-4, IL-5, and IL-13 levels, GATA3, and MUC5AC gene expression, ROS and lung histopathology were studied.
RESULTS
Eosinophil percentage, IgE, IL-4, IL-5, IL-13, and ROS levels, expression of GATA3 and MUC5AC genes, goblet cell hyperplasia, mucus hyper-production, perivascular and peribronchial inflammation were decreased in VIP and VIP-MapA treated groups and treatment with VIP-MapA has a stronger effect than VIP alone.
CONCLUSIONS
The delivery system of VIP carrying to the lung with the use of MapA as an adhesion molecule, could easily carry VIP and led to penetration of this component to the mucus and reach bronchial cells and present an effective, strong, and long-acting effect on therapy of asthma.
PubMed: 37692278
DOI: 10.5114/ada.2023.129458 -
Scientific Reports Oct 2023Although the precise clinical indication for initiation of PMX-HA is widely debated in the literature, a proper patient selection and timing of treatment delivery might... (Observational Study)
Observational Study
Although the precise clinical indication for initiation of PMX-HA is widely debated in the literature, a proper patient selection and timing of treatment delivery might play a critical role in the clinical course of a specific subphenotype of septic shock (endotoxic shock). In light of this view, since 2019, we have introduced in our clinical practice a diagnostic-therapeutic flowchart to select patients that can benefit the most from the treatment proposed. In addition, we reported in this study our experience of PMX-HA in a cohort of critically ill patients admitted to our intensive care unit (ICU). We analyzed a single centre, retrospective, observational web-based database (extracted from the EUPHAS2 registry) of critically ill patients admitted to the ICU between January 2016 and May 2021 who were affected by endotoxic shock. Patients were divided according to the diagnostic-therapeutic flowchart in two groups: Pre-Flowchart (Pre-F) and Post-Flowchart (Post-F). From January 2016 to May 2021, 61 patients were treated with PMX-HA out of 531 patients diagnosed with septic shock and of these, fifty patients (82%) developed AKI during their ICU stay. The most common source of infection was secondary peritonitis (36%), followed by community-acquired pneumonia (29%). Fifty-five (90%) out of 61 patients received a second PMX-HA treatment, with a statistically significant difference between the two groups (78% of the Pre-F vs. 100% of the Post-F group, p = 0.005). In both groups, between T0 and T120, the Endotoxin Activity Assay (EAA) decreased, while the SOFA score, mean arterial pressure (MAP), and Vasoactive Inotropic Score (VIS) improved with no statistically significant difference. Furthermore, when performing a propensity score matching analysis to compare mortality between the two groups, statistically significant lower ICU and 90-day mortalities were observed in the Post-F group [p = 0.016]. Although in this experienced centre data registry, PMX-HA was associated with organ function recovery, hemodynamic improvement, and current EAA level reduction in critically ill patients with endotoxic shock. Following propensity score-matched analysis, ICU mortality and 90-day mortalities were lower in the diagnostic-therapeutic flowchart group when considering two temporal groups based on strict patient selection criteria and timing to achieve PMX. Further Randomised Control Trials focused on centre selection, adequate training and a flowchart of action when assessing extracorporeal blood purification use should be performed.
Topics: Humans; Critical Illness; Endotoxins; Hemoperfusion; Polymyxin B; Retrospective Studies; Shock, Septic
PubMed: 37845296
DOI: 10.1038/s41598-023-44850-9 -
PLoS Biology Aug 2023The central circadian clock of the suprachiasmatic nucleus (SCN) is a network consisting of various types of neurons and glial cells. Individual cells have the...
The central circadian clock of the suprachiasmatic nucleus (SCN) is a network consisting of various types of neurons and glial cells. Individual cells have the autonomous molecular machinery of a cellular clock, but their intrinsic periods vary considerably. Here, we show that arginine vasopressin (AVP) neurons set the ensemble period of the SCN network in vivo to control the circadian behavior rhythm. Artificial lengthening of cellular periods by deleting casein kinase 1 delta (CK1δ) in the whole SCN lengthened the free-running period of behavior rhythm to an extent similar to CK1δ deletion specific to AVP neurons. However, in SCN slices, PER2::LUC reporter rhythms of these mice only partially and transiently recapitulated the period lengthening, showing a dissociation between the SCN shell and core with a period instability in the shell. In contrast, in vivo calcium rhythms of both AVP and vasoactive intestinal peptide (VIP) neurons in the SCN of freely moving mice demonstrated stably lengthened periods similar to the behavioral rhythm upon AVP neuron-specific CK1δ deletion, without changing the phase relationships between each other. Furthermore, optogenetic activation of AVP neurons acutely induced calcium increase in VIP neurons in vivo. These results indicate that AVP neurons regulate other SCN neurons, such as VIP neurons, in vivo and thus act as a primary determinant of the SCN ensemble period.
Topics: Animals; Mice; Arginine Vasopressin; Calcium; Neurons; Suprachiasmatic Nucleus; Neuroglia; Vasoactive Intestinal Peptide
PubMed: 37643163
DOI: 10.1371/journal.pbio.3002281