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Cell Death & Disease May 2024Lupus nephritis (LN) occurs in 50% of cases of systemic lupus erythematosus (SLE) and is one of the most serious complications that can occur during lupus progression....
Lupus nephritis (LN) occurs in 50% of cases of systemic lupus erythematosus (SLE) and is one of the most serious complications that can occur during lupus progression. Mesangial cells (MCs) are intrinsic cells in the kidney that can regulate capillary blood flow, phagocytose apoptotic cells, and secrete vasoactive substances and growth factors. Previous studies have shown that various types of inflammatory cells can activate MCs for hyperproliferation, leading to disruption of the filtration barrier and impairment of renal function in LN. Here, we characterized the heterogeneity of kidney cells of LN mice by single-nucleus RNA sequencing (snRNA-seq) and revealed the interaction between macrophages and MCs through the CXC motif chemokine ligand 12 (CXCL12)/dipeptidyl peptidase 4 (DPP4) axis. In culture, macrophages modulated the proliferation and migration of MCs through this ligand-receptor interaction. In LN mice, treatment with linagliptin, a DPP4 inhibitor, effectively inhibited MC proliferation and reduced urinary protein levels. Together, our findings indicated that targeting the CXCL12/DPP4 axis with linagliptin treatment may serve as a novel strategy for the treatment of LN via the CXCL12/DPP4 axis.
Topics: Lupus Nephritis; Animals; Dipeptidyl Peptidase 4; Chemokine CXCL12; Mesangial Cells; Mice; Macrophages; Cell Proliferation; Humans; Female; Cell Movement; Cell Communication; Linagliptin; Signal Transduction; Dipeptidyl-Peptidase IV Inhibitors; Mice, Inbred C57BL
PubMed: 38762508
DOI: 10.1038/s41419-024-06708-4 -
BMJ Open May 2024Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant... (Review)
Review
INTRODUCTION
Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps.
METHODS AND ANALYSIS
This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care.
ETHICS AND DISSEMINATION
Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.
Topics: Humans; Pneumonectomy; Anesthesia; Pleura; Perioperative Care; Pleural Neoplasms; Postoperative Complications
PubMed: 38760041
DOI: 10.1136/bmjopen-2023-078125 -
Open Forum Infectious Diseases May 2024We sought to assess the performance of commonly used clinical scoring systems to predict imminent clinical deterioration in patients hospitalized with suspected...
BACKGROUND
We sought to assess the performance of commonly used clinical scoring systems to predict imminent clinical deterioration in patients hospitalized with suspected infection in rural Thailand.
METHODS
Patients with suspected infection were prospectively enrolled within 24 hours of admission to a referral hospital in northeastern Thailand between 2013 and 2017. In patients not requiring intensive medical interventions, multiple enrollment scores were calculated including the National Early Warning Score (NEWS), the Modified Early Warning Score, Between the Flags, and the quick Sequential Organ Failure Assessment score. Scores were tested for predictive accuracy of clinical deterioration, defined as a new requirement of mechanical ventilation, vasoactive medications, intensive care unit admission, and/or death approximately 1 day after enrollment. The association of each score with clinical deterioration was evaluated by means of logistic regression, and discrimination was assessed by generating area under the receiver operating characteristic curve.
RESULTS
Of 4989 enrolled patients, 2680 met criteria for secondary analysis, and 100 of 2680 (4%) experienced clinical deterioration within 1 day after enrollment. NEWS had the highest discrimination for predicting clinical deterioration (area under the receiver operating characteristic curve, 0.78 [95% confidence interval, .74-.83]) compared with the Modified Early Warning Score (0.67 [.63-.73]; < .001), quick Sequential Organ Failure Assessment (0.65 [.60-.70]; < .001), and Between the Flags (0.69 [.64-.75]; < .001). NEWS ≥5 yielded optimal sensitivity and specificity for clinical deterioration prediction.
CONCLUSIONS
In patients hospitalized with suspected infection in a resource-limited setting in Southeast Asia, NEWS can identify patients at risk of imminent clinical deterioration with greater accuracy than other clinical scoring systems.
PubMed: 38756761
DOI: 10.1093/ofid/ofae245 -
Heliyon May 2024The aim of this study was to confirm the presence of the form deprivation myopia (FDM) guinea pig eye-gut axis and investigate the relationship between serum vasoactive...
AIM
The aim of this study was to confirm the presence of the form deprivation myopia (FDM) guinea pig eye-gut axis and investigate the relationship between serum vasoactive intestinal peptide (VIP), lipopolysaccharides (LPS), specific gut microbiota and their metabolites.
METHOD
20 specific-pathogen-free (SPF) guinea pigs were divided into the FDM and the control(Con) group. Following model induction, serum levels of VIP and LPS were quantified. A combination of 16S ribosomal ribosomal Ribonucleic Acid (rRNA) gene sequencing, non-targeted metabolomics and bioinformatics analysis were employed to identify disparities in gut microbiota and metabolites between the two groups of guinea pigs.
RESULT
Compared to the control group, FDM guinea pigs exhibited a significant trend towards myopia, along with significantly elevated concentrations of LPS and VIP ( < 0.0001). Furthermore, Ruminococcus_albus emerged as the predominant bacterial community enriched in FDM ( < 0.05), and demonstrated positive correlations with 10 metabolites, including l-Glutamic acid, Additionally, Ruminococcus_albus exhibited positive correlations with VIP and LPS levels ( < 0.05).
CONCLUSION
The findings suggest that the Ruminococcus_Albus and glutamate metabolic pathways play a significant role in myopia development, leading to concurrent alterations in serum VIP and LPS levels in FDM guinea pigs. This underscores the potential of specific gut microbiota and their metabolites as pivotal biomarkers involved in the pathogenesis of myopia.
PubMed: 38756593
DOI: 10.1016/j.heliyon.2024.e30491 -
Brazilian Journal of Cardiovascular... May 2024This study aimed to investigate the predictive value of the vasoactive-inotropic score (VIS) at different time points for postoperative prolonged mechanical ventilation...
Prediction of Vasoactive-Inotropic Score on Prolonged Mechanical Ventilation in Adult Congenital Heart Disease Patients After Surgical Treatment Combined with Coronary Artery Bypass Grafting.
INTRODUCTION
This study aimed to investigate the predictive value of the vasoactive-inotropic score (VIS) at different time points for postoperative prolonged mechanical ventilation (PMV) in adult congenital heart disease patients undergoing surgical treatment combined with coronary artery bypass grafting.
METHODS
Patients were divided into two groups that developed PMV or not. The propensity score matching method was applied to reduce the effects of confounding factors between the two groups. VIS at different time points (VIS at the end of surgery, VIS6h, VIS12h, and VIS12h max) after surgery were recorded and calculated. The value of VIS in predicting PMV was analyzed by the receiver operating characteristic (ROC) curve, and multivariate logistic regression was used to analyze independent risk factors.
RESULTS
Among 250 patients, 52 were in the PMV group, and 198 were in the non-PMV group. PMV rate was 20.8%. After propensity score matching, 94 patients were matched in pairs. At each time point, the area under the ROC curve predicted by VIS for PMV was > 0.500, among which VIS at the end of surgery was the largest (0.805). The optimal cutoff point for VIS of 6.5 could predict PMV with 78.7% sensitivity and 72.3% specificity. VIS at the end of surgery was an independent risk factor for PMV (odds ratio=1.301, 95% confidence interval 1.091~1.551, P<0.01).
CONCLUSION
VIS at the end of surgery is an independent predictor for PMV in patients with adult congenital heart disease surgical treatment combined with coronary artery bypass grafting.
Topics: Humans; Coronary Artery Bypass; Female; Male; Respiration, Artificial; Heart Defects, Congenital; Adult; Middle Aged; Propensity Score; ROC Curve; Risk Factors; Time Factors; Retrospective Studies; Predictive Value of Tests; Postoperative Period; Logistic Models
PubMed: 38748809
DOI: 10.21470/1678-9741-2023-0218 -
Clinical and Translational Science May 2024Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse... (Randomized Controlled Trial)
Randomized Controlled Trial
Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to β-blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vasodilation via incompletely understood mechanisms. This study aimed at identifying pathways underlying ancestral differences in PRA, which might reflect pathways underlying BP-lowering mechanisms of TDs and BBs. Among hypertensive participants enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, we previously identified 8 metabolites associated with baseline PRA and 4 metabolic clusters (including 39 metabolites) that are different between those with GWAA <45% versus ≥45%. In the current study, using Ingenuity Pathway Analysis (IPA), we integrated these signals. Three overlapping metabolic signals within three significantly enriched pathways were identified as associated with both PRA and %GWAA: ceramide signaling, sphingosine 1- phosphate signaling, and endothelial nitric oxide synthase signaling. Literature indicates that the identified pathways are involved in the regulation of the Rho kinase cascade, production of the vasoactive agents nitric oxide, prostacyclin, thromboxane A2, and endothelin 1; the pathways proposed to underlie TD- and BB-induced vasodilatation. These findings may improve our understanding of the BP-lowering mechanisms of TDs and BBs. This might provide a possible step forward in personalizing antihypertensive therapy by identifying patients expected to have robust BP-lowering effects from these drugs.
Topics: Humans; Male; Female; Sodium Chloride Symporter Inhibitors; Hypertension; Blood Pressure; Middle Aged; Metabolomics; Adrenergic beta-Antagonists; Renin; Aged; Nitric Oxide Synthase Type III; Signal Transduction; Adult
PubMed: 38747311
DOI: 10.1111/cts.13816 -
Frontiers in Endocrinology 2024Thin endometrium (TE) is defined as a mid-luteal endometrial thickness ≤7mm. TE can affect endometrial tolerance, leading to lower embryo implantation rates and...
Thin endometrium (TE) is defined as a mid-luteal endometrial thickness ≤7mm. TE can affect endometrial tolerance, leading to lower embryo implantation rates and clinical pregnancy rates, and is also associated with impaired outcomes from assisted reproductive treatment. Herein, we systematically review TE causes, mechanisms, and treatments. TE pathogenesis has multiple causes, with the endometrium becoming thinner with age under hormonal influence. In addition, uterine cavity factors are important, as the inflammatory environment may affect expressions of certain genes thereby inhibiting endometrial stromal cell proliferation and promoting apoptosis. Long-term oral contraceptive use or the use of ovulation-promoting drugs are also definite factors contributing to endometrial thinning. Other patients have primary factors, for which the clinical etiology remains unknown. The main therapeutic strategies available for TE are pharmacological (including hormonal and vasoactive drugs), regenerative medicine, intrauterine infusion of growth factor-granulocyte colony-stimulating factor, autologous platelet-rich plasma, and complementary alternative therapies (including traditional Chinese herbal medicine and acupuncture). However, the associated mechanisms of action are currently unclear. Clinical scholars have proposed various approaches to improve treatment outcomes in patients with TE, and are exploring the principles of efficacy, offering potentials for novel treatments. It is hoped that this will improve TE tolerance, increase embryo implantation rates, and help more couples with infertility with effective treatments.
Topics: Female; Humans; Pregnancy; Embryo Implantation; Endometrium; Infertility, Female
PubMed: 38745960
DOI: 10.3389/fendo.2024.1269382 -
Cell Reports May 2024Diverse types of inhibitory interneurons (INs) impart computational power and flexibility to neocortical circuits. Whereas markers for different IN types in cortical...
Diverse types of inhibitory interneurons (INs) impart computational power and flexibility to neocortical circuits. Whereas markers for different IN types in cortical layers 2-6 (L2-L6) have been instrumental for generating a wealth of functional insights, only the recent identification of a selective marker (neuron-derived neurotrophic factor [NDNF]) has opened comparable opportunities for INs in L1 (L1INs). However, at present we know very little about the connectivity of NDNF L1INs with other IN types, their input-output conversion, and the existence of potential NDNF L1IN subtypes. Here, we report pervasive inhibition of L2/3 INs (including parvalbumin INs and vasoactive intestinal peptide INs) by NDNF L1INs. Intersectional genetics revealed similar physiology and connectivity in the NDNF L1IN subpopulation co-expressing neuropeptide Y. Finally, NDNF L1INs prominently and selectively engage in persistent firing, a physiological hallmark disconnecting their output from the current input. Collectively, our work therefore identifies NDNF L1INs as specialized master regulators of superficial neocortex according to their pervasive top-down afferents.
Topics: Interneurons; Animals; Mice; Neuropeptide Y; Neocortex; Vasoactive Intestinal Peptide; Male; Parvalbumins
PubMed: 38743567
DOI: 10.1016/j.celrep.2024.114212 -
Journal of the Intensive Care Society May 2024Despite high rates of cardiovascular disease in Scotland, the prevalence and outcomes of patients with cardiogenic shock are unknown.
EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS): A multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland.
BACKGROUND
Despite high rates of cardiovascular disease in Scotland, the prevalence and outcomes of patients with cardiogenic shock are unknown.
METHODS
We undertook a prospective observational cohort study of consecutive patients with cardiogenic shock admitted to the intensive care unit (ICU) or coronary care unit at 13 hospitals in Scotland for a 6-month period. Denominator data from the Scottish Intensive Care Society Audit Group were used to estimate ICU prevalence; data for coronary care units were unavailable. We undertook multivariable logistic regression to identify factors associated with in-hospital mortality.
RESULTS
In total, 247 patients with cardiogenic shock were included. After exclusion of coronary care unit admissions, this comprised 3.0% of all ICU admissions during the study period (95% confidence interval [CI] 2.6%-3.5%). Aetiology was acute myocardial infarction (AMI) in 48%. The commonest vasoactive treatment was noradrenaline (56%) followed by adrenaline (46%) and dobutamine (40%). Mechanical circulatory support was used in 30%. Overall in-hospital mortality was 55%. After multivariable logistic regression, age (odds ratio [OR] 1.04, 95% CI 1.02-1.06), admission lactate (OR 1.10, 95% CI 1.05-1.19), Society for Cardiovascular Angiographic Intervention stage D or E at presentation (OR 2.16, 95% CI 1.10-4.29) and use of adrenaline (OR 2.73, 95% CI 1.40-5.40) were associated with mortality.
CONCLUSIONS
In Scotland the prevalence of cardiogenic shock was 3% of all ICU admissions; more than half died prior to discharge. There was significant variation in treatment approaches, particularly with respect to vasoactive support strategy.
PubMed: 38737313
DOI: 10.1177/17511437231217877 -
Therapeutics and Clinical Risk... 2024The impact of coagulation indicators on postoperative outcomes of patients with constrictive pericarditis undergoing pericardiectomy has been poorly investigated. This...
BACKGROUND
The impact of coagulation indicators on postoperative outcomes of patients with constrictive pericarditis undergoing pericardiectomy has been poorly investigated. This study aimed to assess the prognostic role of preoperative coagulation indicators in these patients.
METHODS
We retrospectively included 158 patients with constrictive pericarditis undergoing pericardiectomy. The diagnostic values of coagulation indicators for postoperative complications were evaluated by ROC curves. Patients were divided into two groups according to the cutoff value calculated by ROC curve. Postoperative outcomes were compared between the two groups. Logistic regression analysis was performed to identify risk factors of postoperative complications.
RESULTS
ROC curve showed that among different coagulation indicators, preoperative D-dimer (DD) level could effectively identify patients with postoperative complications (AUC 0.771, 95% CI 0.696-0.847, P < 0.001). Patients were divided into the low DD group and the high DD group. The comparison of postoperative outcomes suggested that high preoperative DD level was significantly associated with longer durations of vasoactive agents using (P = 0.018), intubation (P = 0.020), ICU stay (P = 0.008), chest drainage (P=0.004) and hospital stay (P = 0.002). Multivariable analysis showed that high preoperative DD level was the independent risk factor of postoperative complications (OR 6.892, 95% CI 2.604-18.235, P < 0.001).
CONCLUSION
High preoperative DD level was significantly linked to poor postoperative outcomes and could provide an effective prediction ability for postoperative complications in patients with constrictive pericarditis.
PubMed: 38736988
DOI: 10.2147/TCRM.S462075