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BMJ Open May 2024This study aimed to describe the clinical characteristics of adults with suspected acute community-acquired pneumonia (CAP) on hospitalisation, evaluate their prediction...
Community-acquired pneumonia: use of clinical characteristics of acutely admitted patients for the development of a diagnostic model - a cross-sectional multicentre study.
OBJECTIVES
This study aimed to describe the clinical characteristics of adults with suspected acute community-acquired pneumonia (CAP) on hospitalisation, evaluate their prediction performance for CAP and compare the performance of the model to the initial assessment of the physician.
DESIGN
Cross-sectional, multicentre study.
SETTING
The data originated from the INfectious DisEases in Emergency Departments study and were collected prospectively from patient interviews and medical records. The study included four Danish medical emergency departments (EDs) and was conducted between 1 March 2021 and 28 February 2022.
PARTICIPANTS
A total of 954 patients admitted with suspected infection were included in the study.
PRIMARY AND SECONDARY OUTCOME
The primary outcome was CAP diagnosis assessed by an expert panel.
RESULTS
According to expert evaluation, CAP had a 28% prevalence. 13 diagnostic predictors were identified using least absolute shrinkage and selection operator regression to build the prediction model: dyspnoea, expectoration, cough, common cold, malaise, chest pain, respiratory rate (>20 breaths/min), oxygen saturation (<96%), abnormal chest auscultation, leucocytes (<3.5×10/L or >8.8×10/L) and neutrophils (>7.5×10/L). C reactive protein (<20 mg/L) and having no previous event of CAP contributed negatively to the final model. The predictors yielded good prediction performance for CAP with an area under the receiver-operator characteristic curve (AUC) of 0.85 (CI 0.77 to 0.92). However, the initial diagnosis made by the ED physician performed better, with an AUC of 0.86 (CI 84% to 89%).
CONCLUSION
Typical respiratory symptoms combined with abnormal vital signs and elevated infection biomarkers were predictors for CAP on admission to an ED. The clinical value of the prediction model is questionable in our setting as it does not outperform the clinician's assessment. Further studies that add novel diagnostic tools and use imaging or serological markers are needed to improve a model that would help diagnose CAP in an ED setting more accurately.
TRIAL REGISTRATION NUMBER
NCT04681963.
Topics: Humans; Community-Acquired Infections; Cross-Sectional Studies; Male; Female; Middle Aged; Aged; Pneumonia; Emergency Service, Hospital; Hospitalization; Denmark; Adult; ROC Curve; Prospective Studies; C-Reactive Protein
PubMed: 38816044
DOI: 10.1136/bmjopen-2023-079123 -
Redox Biology May 2024Hypoxia-inducible factor 1 alpha (HIF-1α) is a major molecular mediator of the hypoxic response. In the endometrium, local hypoxic conditions induced by hormonal... (Review)
Review
Hypoxia-inducible factor 1 alpha (HIF-1α) is a major molecular mediator of the hypoxic response. In the endometrium, local hypoxic conditions induced by hormonal fluctuations and endometrial vascular remodeling contribute to the production of HIF-1α, which plays an indispensable role in a series of physiological activities, such as menstruation and metamorphosis. The sensitive regulation of HIF-1α maintains the cellular viability and regenerative capacity of the endometrium against cellular stresses induced by hypoxia and excess reactive oxygen species. In contrast, abnormal HIF-1α levels exacerbate the development of various endometrial pathologies. This knowledge opens important possibilities for the development of promising HIF-1α-centered strategies to ameliorate endometrial disease. Nonetheless, additional efforts are required to elucidate the regulatory network of endometrial HIF-1α and promote the applications of HIF-1α-centered strategies in the human endometrium. Here, we summarize the role of the HIF-1α-mediated pathway in endometrial physiology and pathology, highlight the latest HIF-1α-centered strategies for treating endometrial diseases, and improve endometrial receptivity.
PubMed: 38815332
DOI: 10.1016/j.redox.2024.103205 -
Redox Biology May 2024Cysteine, the rate-controlling amino acid in cellular glutathione synthesis is imported as cystine, by the cystine/glutamate antiporter, xCT, and subsequently reduced to...
Cysteine, the rate-controlling amino acid in cellular glutathione synthesis is imported as cystine, by the cystine/glutamate antiporter, xCT, and subsequently reduced to cysteine. As glutathione redox is important in muscle regeneration in aging, we hypothesized that xCT exerts upstream control over skeletal muscle glutathione redox, metabolism and regeneration. Bioinformatic analyses of publicly available datasets revealed that expression levels of xCT and GSH-related genes are inversely correlated with myogenic differentiation genes. Muscle satellite cells (MuSCs) isolated from Slc7a11 mice, which harbour a mutation in the Slc7a11 gene encoding xCT, required media supplementation with 2-mercaptoethanol to support cell proliferation but not myotube differentiation, despite persistently lower GSH. Slc7a11 primary myotubes were larger compared to WT myotubes, and also exhibited higher glucose uptake and cellular oxidative capacities. Immunostaining of myogenic markers (Pax7, MyoD, and myogenin) in cardiotoxin-damaged tibialis anterior muscle fibres revealed greater MuSC activation and commitment to differentiation in Slc7a11 muscle compared to WT mice, culminating in larger myofiber cross-sectional areas at 21 days post-injury. Slc7a11 mice subjected to a 5-week exercise training protocol demonstrated enhanced insulin tolerance compared to WT mice, but blunted muscle mitochondrial biogenesis and respiration in response to exercise training. Our results demonstrate that the absence of xCT inhibits cell proliferation but promotes myotube differentiation by regulating cellular metabolism and glutathione redox. Altogether, these results support the notion that myogenesis is a redox-regulated process and may help inform novel therapeutic approaches for muscle wasting and dysfunction in aging and disease.
PubMed: 38815331
DOI: 10.1016/j.redox.2024.103213 -
PloS One 2024Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally...
Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally occurring naphthoquinone in J. mandshurica, exhibits significant cytotoxic activity against various cancer cell lines. However, whether the anticancer activity of juglone is associated with oxidative stress remains unexplored. In this study, mouse Lewis lung cancer (LLC) and human non-small cell lung cancer A549 cells were used to explore the anticancer mechanisms of juglone. Juglone inhibited LLC and A549 cells viability, with IC50 values of 10.78 μM and 9.47 μM, respectively, for 24 h, and substantially suppressed the migration and invasion of these two lung cancer cells. Additionally, juglone arrested the cell cycle, induced apoptosis, increased the cleavage of caspase 3 and the protein expression of Bax and Cyt c, and decreased the protein expression of Bcl-2 and caspase-3. Furthermore, juglone treatment considerably increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, but suppressed glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD) activities. It also inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which was attenuated by 1,3-diCQA (an activator of PI3K/Akt). Moreover, N-acetylcysteine (a ROS scavenger) partially reversed the positive effects of juglone in terms of migration, invasion, ROS production, apoptosis, and PI3K/Akt pathway-associated protein expression. Finally, in tumor-bearing nude mouse models, juglone inhibited tumor growth without any apparent toxicity and significantly induced apoptosis in NSCLC cells. Collectively, our findings suggest that juglone triggers apoptosis via the ROS-mediated PI3K/Akt pathway. Therefore, juglone may serve as a potential therapeutic agent for the treatment of NSCLC.
Topics: Naphthoquinones; Carcinoma, Non-Small-Cell Lung; Reactive Oxygen Species; Humans; Animals; Apoptosis; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Lung Neoplasms; Mice; Signal Transduction; A549 Cells; Cell Movement; Carcinoma, Lewis Lung; Cell Line, Tumor
PubMed: 38814975
DOI: 10.1371/journal.pone.0299921 -
PloS One 2024To investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory... (Comparative Study)
Comparative Study
OBJECTIVE
To investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory failure requiring mechanical ventilation support and to assess the predictive capability of OSI in determining clinically relevant OI cutoffs.
METHODS
A prospective study was conducted on neonates who received invasive mechanical ventilation at the neonatal intensive care unit of tertiary hospital in Vietnam. Bland-Altman analysis was utilized to evaluate the agreement between OSI and OI.
RESULTS
A total of 123 neonates, including both term and preterm infants, were included in the study. A high agreement rate of 94.3% within the 95% limits of agreement (between OI and OSI), with a narrow similarity value of 3.3 (95% CI: -5.1 to 11.8) and high correlation coefficient (r = 0.791, p<0.001) was observed. The OSI cut-off value for predicting an OI of >15 was determined to be 7.45, with a sensitivity of 100% and a specificity of 87.4% (AUC 0.955; 95% CI: 0.922-0.989, p < 0.05). Similarly, an OSI cutoff value of 9.9 corresponded to an OI of 25, displaying a sensitivity of 100% and specificity of 87.4% (AUC 0.92). The receiver operating characteristic (ROC) curves for OSI exhibited statistically significant results (p < 0.05).
CONCLUSION
The findings demonstrate a strong correlation between OSI and OI in neonates with respiratory failure. Furthermore, OSI, as a non-invasive method, can serve as a substitute for OI to evaluate the severity of hypoxic respiratory failure and lung injury in neonates.
Topics: Humans; Infant, Newborn; Respiration, Artificial; Respiratory Insufficiency; Male; Female; Prospective Studies; Oxygen Saturation; Hypoxia; Oxygen; Intensive Care Units, Neonatal; Infant, Premature; ROC Curve
PubMed: 38814919
DOI: 10.1371/journal.pone.0304278 -
Blood Transfusion = Trasfusione Del... May 2024Quality assessment of modified or processed red blood cell (RBC) components, such as pathogen-reduced RBCs, using only in vitro testing may not always be predictive of...
BACKGROUND
Quality assessment of modified or processed red blood cell (RBC) components, such as pathogen-reduced RBCs, using only in vitro testing may not always be predictive of in vivo performance. Mouse or rat in vivo models are limited by a lack of applicability to certain aspects of human RBC biology. Here, we used a guinea pig model to study the effects of riboflavin combined with UV light on the integrity of RBCs in vitro and following transfusion in vivo.
MATERIALS AND METHODS
Guinea pig RBCs were collected from whole blood (WB) treated with varying UV doses (10, 20, 40 or 80 J/mL) in the presence of riboflavin (UVR-RBCs). In vitro tests for UVR-RBCs included hemolysis, osmotic fragility, and cellular morphology by scanning electron microscopy. Guinea pigs transfused with one-day post-treatment UVR-RBCs were evaluated for plasma hemoglobin (Hb), non-transferrin bound iron (NTBI), total iron and Perls-detectable hemosiderin deposition in the spleen and kidney, and renal uptake of Hb.
RESULTS
Acute RBC injury was dose dependently accelerated after treatment with UV light in the presence of riboflavin. Aberrant RBC morphology was evident at 20, 40, and 80 J/mL, and membrane lysis with Hb release was prominent at 80 J/mL. Guinea pigs transfused with 40 and 80 J/mL UVR-RBCs showed increased plasma Hb levels, and plasma NTBI was elevated in all UVR-RBC groups (10-80 J/mL). Total iron levels and Perls-hemosiderin staining in spleen and kidney as well as Hb uptake in renal proximal tubules were increased 8 hours post-transfusion with 40 and 80 J/mL UVR-RBCs.
DISCUSSION
UVR-RBCs administered to guinea pigs increased markers of intravascular and extravascular hemolysis in a UV dose-dependent manner. This model may allow for the discrimination of RBC injury during testing of extensively processed RBCs intended for transfusion.
PubMed: 38814883
DOI: 10.2450/BloodTransfus.718 -
The Turkish Journal of Pediatrics May 2024Due to their relationship with clinical progression, follow-up of exercise capacity and muscle strength is important for optimal disease management in patients who have...
BACKGROUND
Due to their relationship with clinical progression, follow-up of exercise capacity and muscle strength is important for optimal disease management in patients who have undergone the Fontan procedure. We aimed to retrospectively analyze exercise capacity and muscle strength trajectory over approximately 2 years.
METHODS
Exercise capacity was assessed using an exercise stress test with the modified Bruce protocol on a treadmill, hand grip and knee extensor strength using a hand dynamometer, and body composition using a bioelectrical impedance device. Exercise capacity, muscle strength, and body composition follow-up data recorded between 2020 and 2022 were compared.
RESULTS
Fifteen patients [median age from 17 (first assessment) to 18 years (last assessment), 5 females)] with a 20-month median follow-up time were analyzed retrospectively. There was an increase in weight, height, body mass index, and body fat weight (p<0.05). There was a tendency for increased handgrip strength (%) (p=0.069), but no significant difference was observed in the knee extensor strength of patients during the follow-up period (p>0.05). The changes in heart rate (HR) and oxygen saturation were higher in the last test than in the first test (p<0.05). Maximum HR (HRmax), % predicted HRmax and HR reserve recorded during the test and HR 1 minute after the test were similar between the first and last tests (p>0.05).
CONCLUSIONS
After 20 months of follow-up, exercise capacity and muscle strength did not decline; instead, the body mass index and fat weight increased. Patients who have undergone the Fontan procedure may not be experiencing a decline in exercise capacity and muscle strength over relatively short time periods during childhood, adolescence, and early adulthood.
Topics: Humans; Fontan Procedure; Female; Male; Retrospective Studies; Muscle Strength; Adolescent; Follow-Up Studies; Exercise Tolerance; Exercise Test; Hand Strength; Body Composition
PubMed: 38814303
DOI: 10.24953/turkjpediatr.2024.4570 -
The Turkish Journal of Pediatrics May 2024Acute respiratory failure is a prevalent condition in childhood with a high rate of mortality. Invasive mechanical ventilation support may be required for the management...
BACKGROUND
Acute respiratory failure is a prevalent condition in childhood with a high rate of mortality. Invasive mechanical ventilation support may be required for the management of these patients. Extracorporeal membrane oxygenation (ECMO) is a method used when ventilation support is insufficient. However, the less invasive extracorporeal carbon dioxide removal method can be used as an alternative in cases of hypercapnic respiratory failure.
CASE
A 9-year-old patient with cystic fibrosis presented to the hospital with acute respiratory failure due to pneumonia. Bilateral patchy areas of consolidation were evident in the chest x-ray. Invasive mechanical ventilation support was consequently provided to treat severe hypercapnia. Although peak and plateau pressure levels exceeded 32 cmH₂O (49 cmH₂O) and 28 cmH₂O (35 cmH₂O), respectively, the patient continued to have severe respiratory acidosis. Therefore extracorporeal carbon dioxide removal support was initiated to provide lung-protective ventilation. By Day 10, venovenous ECMO support was initiated due to deteriorating oxygenation.
CONCLUSION
In cases where conventional invasive mechanical ventilation support is insufficient due to acute hypercapnic respiratory failure, extracorporeal carbon dioxide removal support, which is less invasive compared to ECMO, should be considered as an effective and reliable alternative method. However, it should be noted that extracorporeal carbon dioxide removal support does not affect oxygenation; it functions solely as a carbon dioxide removal system.
Topics: Humans; Cystic Fibrosis; Respiratory Insufficiency; Extracorporeal Membrane Oxygenation; Hypercapnia; Child; Carbon Dioxide; Male; Acute Disease; Respiration, Artificial
PubMed: 38814300
DOI: 10.24953/turkjpediatr.2024.4588 -
MBio May 2024is a typical necrotrophic plant pathogenic fungus which can deliberately acidify host tissues and trigger oxidative bursts therein to facilitate its virulence. The...
is a typical necrotrophic plant pathogenic fungus which can deliberately acidify host tissues and trigger oxidative bursts therein to facilitate its virulence. The white collar complex (WCC), consisting of BcWCL1 and BcWCL2, is recognized as the primary light receptor in . Nevertheless, the specific mechanisms through which the WCC components, particularly BcWCL2 as a GATA transcription factor, control virulence are not yet fully understood. This study demonstrates that deletion of BcWCL2 results in the loss of light-sensitive phenotypic characteristics. Additionally, the Δ strain exhibits reduced secretion of citrate, delayed infection cushion development, weaker hyphal penetration, and decreased virulence. The application of exogenous citric acid was found to restore infection cushion formation, hyphal penetration, and virulence of the Δ strain. Transcriptome analysis at 48 h post-inoculation revealed that two citrate synthases, putative citrate transporters, hydrolytic enzymes, and reactive oxygen species scavenging-related genes were down-regulated in Δ, whereas exogenous citric acid application restored the expression of the above genes involved in the early infection process of Δ. Moreover, the expression of , a known regulator of citrate secretion, tissue acidification, and secondary metabolism, was down-regulated in Δ but not in Δ. ChIP-qPCR and electrophoretic mobility shift assays revealed that BcWCL2 can bind to the promoter sequences of . Overexpressing in Δ was found to rescue the mutant defects. Collectively, our findings indicate that BcWCL2 regulates the expression of the global regulator to influence citrate secretion, tissue acidification, redox homeostasis, and virulence of .IMPORTANCEThis study illustrated the significance of the fungal blue light receptor component BcWCL2 protein in regulating citrate secretion in . Unlike BcWCL1, BcWCL2 may contribute to redox homeostasis maintenance during infection cushion formation, ultimately proving to be essential for full virulence. It is also demonstrated that BcWCL2 can regulate the expression of to influence host tissue acidification, citrate secretion, infection cushion development, and virulence. While the role of organic acids secreted by plant pathogenic fungi in fungus-host interactions has been recognized, this paper revealed the importance, regulatory mechanisms, and key transcription factors that control organic acid secretion. These understanding of the pathogenetic mechanism of plant pathogens can provide valuable insights for developing effective prevention and treatment strategies against fungal diseases.
PubMed: 38814088
DOI: 10.1128/mbio.00133-24 -
Journal of Investigative Medicine High... 2024Hemophagocytic lymphohistiocytosis (HLH) secondary to is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH... (Review)
Review
Hemophagocytic lymphohistiocytosis (HLH) secondary to is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH secondary to , affecting a 57-year-old female with rheumatoid arthritis. Extensive investigations were unrevealing and despite broad-spectrum antibiotics, her condition worsened, leading to respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support, shock requiring multiple vasopressors, and acute kidney injury (AKI) requiring hemodialysis. Diagnosis confirmed disseminated histoplasmosis (DHP), prompting Amphotericin B and methylprednisolone treatment, resulting in significant improvement and discharge with posaconazole therapy. Secondary HLH, primarily arising from severe infections like DHP, is discussed. Limited research exists on this condition in human immunodeficiency virus (HIV)-seronegative individuals. Diagnosis involves HLH-2004 and HScore criteria. Managing histoplasmosis-associated HLH remains challenging due to multiorgan failure risks and treatment complexities and needs further research.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Histoplasmosis; Female; Middle Aged; Antifungal Agents; Histoplasma; Amphotericin B
PubMed: 38813977
DOI: 10.1177/23247096241258074