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MBio Jul 2024pneumonia (PjP) poses a serious risk to individuals with compromised immune systems, such as individuals with HIV/AIDS or undergoing immunosuppressive therapies for...
pneumonia (PjP) poses a serious risk to individuals with compromised immune systems, such as individuals with HIV/AIDS or undergoing immunosuppressive therapies for cancer or solid organ transplants. Severe PjP triggers excessive lung inflammation, resulting in lung function decline and consequential alveolar damage, potentially culminating in acute respiratory distress syndrome. Non-HIV patients face a 30%-60% mortality rate, emphasizing the need for a deeper understanding of inflammatory responses in PjP. Prior research emphasized macrophages in infections, neglecting neutrophils' role in tissue damage. Consequently, the overemphasis on macrophages led to an incomplete understanding of the role of neutrophils and inflammatory responses. In the current investigation, our RNAseq studies on a murine surrogate model of PjP revealed heightened activation of the NLRP3 inflammasome and NETosis cell death pathways in their lungs. Immunofluorescence staining confirmed neutrophil extracellular trap (NET) presence in the lungs of the -infected mice, validating our findings. Moreover, isolated neutrophils exhibited NETosis when directly stimulated with . Isolated NETs compromised viability , highlighting the potential role of neutrophils in controlling fungal growth and promoting inflammation during pneumonia through NLRP3 inflammasome assembly and NETosis. These pathways, essential for inflammation and pathogen elimination, bear the risk of uncontrolled activation leading to excessive tissue damage and persistent inflammation. This pioneering study is the first to identify the formation of NETs and inflammasomes during infection, paving the way for comprehensive investigations into treatments aimed at mitigating lung damage and augmenting survival rates for individuals with .IMPORTANCE pneumonia (PjP) affects individuals with weakened immunity, such as HIV/AIDS, cancer, and organ transplant patients. Severe PjP triggers lung inflammation, impairing function and potentially causing acute respiratory distress syndrome. Non-HIV individuals face a 30%-60% mortality rate, underscoring the need for deeper insight into PjP's inflammatory responses. Past research focused on macrophages in managing infection and its inflammation, while the role of neutrophils was generally overlooked. In contrast, our findings in -infected mouse lungs showed neutrophil involvement during inflammation and increased expression of NLRP3 inflammasome and NETosis pathways. Detection of neutrophil extracellular traps further indicated their involvement in the inflammatory process. Although beneficial in combating infection, unregulated neutrophil activation poses a potential threat to lung tissues. Understanding the behavior of neutrophils in infections is crucial for controlling detrimental reactions and formulating treatments to reduce lung damage, ultimately improving the survival rates of individuals with PjP.
PubMed: 38953359
DOI: 10.1128/mbio.01409-24 -
Lung India : Official Organ of Indian... Jul 2024Weaning protocols from Non-invasive ventilation (NIV) are scant. We set out to study a protocol that was different from the British Thoracic Society protocol and lay...
BACKGROUND
Weaning protocols from Non-invasive ventilation (NIV) are scant. We set out to study a protocol that was different from the British Thoracic Society protocol and lay down a weaning protocol from NIV in patients with Acute acidotic hypercapnic respiratory failure (AAHRF).
MATERIALS AND METHODS
Patients admitted with AAHRF and treated with NIV (baseline pH<7.35, PaCO2 >45 mmHg, and not requiring intubation) at a tertiary care teaching hospital, after taking into consideration the inclusion and the exclusion criteria were randomised in to one of the two group of weaning form NIV and serial ABGs were monitored.
RESULTS
The primary outcome of the study shows that there was no significant differences in the success rates of weaning from NIV in both the arms. The secondary outcome shows a few factors such as age, gender, SAPS2 score having an effect on the determination of weaning failure.
CONCLUSION
Our study showed that both weaning by duration reduction and pressure reduction had equal success rates but a point on noting the SAPS II score on admission and the age of a particular patient will help decide on weaning initiation.CTRI/2019/12/022560 [Registered on: 30/12/2019].
PubMed: 38953192
DOI: 10.4103/lungindia.lungindia_15_24 -
Lung India : Official Organ of Indian... Jul 2024Defensins are key effector molecules of innate immunity that can contribute towards the diagnosis and monitoring of chronic obstructive pulmonary disease (COPD). The...
BACKGROUND
Defensins are key effector molecules of innate immunity that can contribute towards the diagnosis and monitoring of chronic obstructive pulmonary disease (COPD). The present study was conducted to investigate the role of alpha-defensins in patients with COPD by quantifying serum and sputum samples.
METHODS
A total of 180 patients were enrolled and divided into four groups, and sputum and serum values of alpha-defensins were assessed. The sensitivity, specificity, and accuracy of sputum alpha-defensin as a diagnostic biomarker were evaluated to assess its utility in diagnosing COPD.
RESULTS
The mean value of sputum alpha-defensins was found to be statistically significant amongst the four groups (P < 0.001). The highest levels were found in subjects with AECOPD (385.76 ± 116.62 ng/mL). Sputum alpha-defensins were found to be negatively correlated with FEV 1 values (rho = -0.31, P < 0.001).
CONCLUSION
Sputum alpha-defensins can be used as a potential marker for predicting acute exacerbation of COPD. In addition, they could serve as an indicator of disease severity in COPD patients.
PubMed: 38953188
DOI: 10.4103/lungindia.lungindia_395_23 -
Infection and Drug Resistance 2024spp. infections have recently increased, and they are difficult to treat because of intrinsic antimicrobial resistance. This study aimed to investigate the clinical...
PURPOSE
spp. infections have recently increased, and they are difficult to treat because of intrinsic antimicrobial resistance. This study aimed to investigate the clinical characteristics of patients with pulmonary infection with spp. and reveal the risk factors for infection and death.
PATIENTS AND METHODS
In this retrospective case-control study, patients were divided into infection and control groups based on the bacterial identification results. Patients in the infection group were further divided into survival and death groups according to their hospital outcomes. Clinical characteristics between different groups were compared. We further analyzed antimicrobial susceptibility testing results of the isolated strains.
RESULTS
A total of the 316 patients were divided into infection (n = 79), 23 of whom died, and control (n = 237) groups. Multivariate logistic regression analysis showed that glucocorticoid consumption (OR: 2.35; 95% CI: 1.14-4.81; P = 0.02), endotracheal intubation (OR: 3.74; 95% CI: 1.62-8.64; P = 0.002), and colistin exposure (OR: 2.50; 95% CI: 1.01-6.29; P = 0.046) were significantly associated with pulmonary infection with spp. Advanced age (OR: 1.07, 95% CI: 1.00-1.15; P = 0.046), high acute physiology and chronic health evaluation (APACHE) II score (OR: 1.21; 95% CI: 1.01-1.45; P = 0.037), and low albumin level (OR: 0.73, 95% CI: 0.56-0.96; P = 0.025) were significantly associated with in-hospital mortality of infected patients. spp. was highly resistant to cephalosporins, carbapenems, macrolides, and aminoglycoside, and was sensitive to fluoroquinolones, minocycline, and co-trimoxazole in vitro.
CONCLUSION
Glucocorticoid consumption, tracheal intubation, and colistin exposure were associated with pulmonary infection with spp. for critically ill patients. Patients with advanced age, high APACHE II score, and low albumin level had higher risk of death from infection.
PubMed: 38953097
DOI: 10.2147/IDR.S460640 -
Infection and Drug Resistance 2024The occurrence and dissemination of hypermucoviscous and hypervirulent (hm-hvKp) isolates in clinical settings are a critical public health problem in the world....
BACKGROUND
The occurrence and dissemination of hypermucoviscous and hypervirulent (hm-hvKp) isolates in clinical settings are a critical public health problem in the world. However, the data on these isolates in community populations are limited. This study aims to understand the prevalence and molecular characteristics of hm-hvKp isolates in community patients in Shanghai, China.
METHODS
In 2018, an active surveillance system focused on hm-hvKp in community diarrhoeal cases was implemented in Pudong New Area, Shanghai, China, involving 12 sentinel hospitals. The antimicrobial susceptibility of hm-hvKp isolates from fecal samples was tested, and whole-genome sequencing (WGS) was performed to predict the serotypes and sequence types and to identify antimicrobial resistance determinants, virulence determinants, and phylogenetic clusters.
RESULTS
The overall prevalence of hm isolates was 2.48% (31/1252), with the proportions of 1.76% (22/1252) for hm-hvKp and 0.72% (9/1252) for hm not hv . The prevalence of hm-hvKp isolates among different age groups and different months was statistically significant. All the 22 hm-hvKp isolates were susceptible to 20 antimicrobial agents and only carried gene, and KL1 and KL2 accounted for eight (36.36%) cases and seven (31.82%) cases, respectively. The eight ST23/KL1 isolates belonged to the predominant CG23-I clade, which typically possessed the virulence determinants profile of /. The five ST86/KL2 isolates were assigned to the global clusters ST86/KL2-1 (n=2), ST86/KL2-2 (n=2), ST86/KL2-3 (n=1), all lack of the gene. Shanghai ST23/KL1 and ST86/KL2 isolates were closely related to the global isolates from liver abscesses, blood, and urine.
CONCLUSION
Hm-hvKp is carried by the community population of Shanghai, with ST23/KL1 and ST86/KL2 isolates predominant. Hm-hvKp isolates of different continents, different sources, and different virulence levels were closely related. Ongoing surveillance of hm-hvKp isolates in the community population is warranted.
PubMed: 38953096
DOI: 10.2147/IDR.S468482 -
Risk Management and Healthcare Policy 2024The Sars-CoV-2 pandemic imposed unprecedented and drastic changes in health care organizations all over the world.
BACKGROUND
The Sars-CoV-2 pandemic imposed unprecedented and drastic changes in health care organizations all over the world.
PURPOSE
To evaluate the impact of the pandemic on hospitalizations in an acute psychiatric ward.
PATIENTS AND METHODS
We retrospectively identified and compared acute psychiatric hospitalizations in the Service for Psychiatric Diagnosis and Care (SPDC) of AUSL-Modena during the pre-pandemic (n = 1858) and pandemic period (n = 1095), from 01/01/2017 to 31/12/2022. Data were statistically analyzed using STATA12.
RESULTS
We collected 1858 hospitalizations in the pre-pandemic and 1095 in the pandemic. During the pandemic, we observed a progressively sharp reduction in voluntary hospitalizations, whereas involuntary ones remained stable with an increase in 2022 (p < 0.001), longer hospital stays (12.32 mean days vs 10.03; p < 0.001), longer periods of involuntary hospitalizations (8.45 mean days vs 5.72; p < 0.001), more frequent aggressive behaviour (16.10% vs 9.12%; p < 0.001) and referral to psychiatric communities at discharge (11.04% vs 6.13%; p < 0.001); non-Italians (p = 0.001), people with disability pension (p < 0.001) and Support Administrator (p < 0.001) were more frequently hospitalized.
CONCLUSION
During the pandemic, voluntary psychiatric hospitalizations decreased, but not involuntary ones, and the most vulnerable people in serious clinical conditions were hospitalized.
PubMed: 38953036
DOI: 10.2147/RMHP.S465858 -
Frontiers in Immunology 2024Schistosomiasis (SM) is a parasitic disease caused by . SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma...
INTRODUCTION
Schistosomiasis (SM) is a parasitic disease caused by . SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma process in the liver, spleen, central nervous system, kidneys, and lungs. Pulmonary arterial hypertension (PAH) is a clinical manifestation characterized by high pressure in the pulmonary circulation and right ventricular overload. This study investigated the production of functional autoantibodies (fAABs) against the second loop of the G-protein-coupled receptor (GPCR) in the presence of hepatic and PAH forms of human SM.
METHODS
Uninfected and infected individuals presenting acute and chronic manifestations (e.g., hepatointestinal, hepato-splenic without PAH, and hepato-splenic with PAH) of SM were clinically evaluated and their blood was collected to identify fAABs/GPCRs capable of recognizing endothelin 1, angiotensin II, and a-1 adrenergic receptor. Human serum was analyzed in rat cardiomyocytes cultured in the presence of the receptor antagonists urapidil, losartan, and BQ123.
RESULTS
The fAABs/GPCRs from chronic hepatic and PAH SM individuals, but not from acute SM individuals, recognized the three receptors. In the presence of the antagonists, there was a reduction in beating rate changes in cultured cardiomyocytes. In addition, binding sites on the extracellular domain functionality of fAABs were identified, and IgG1 and/or IgG3 antibodies were found to be related to fAABs.
CONCLUSION
Our data suggest that fAABs against GPCR play an essential role in vascular activity in chronic SM (hepatic and PAH) and might be involved in the development of hypertensive forms of SM.
Topics: Autoantibodies; Humans; Animals; Receptors, G-Protein-Coupled; Rats; Male; Female; Adult; Hypertension, Pulmonary; Middle Aged; Myocytes, Cardiac; Schistosomiasis mansoni; Schistosoma mansoni; Schistosomiasis
PubMed: 38953035
DOI: 10.3389/fimmu.2024.1404384 -
Frontiers in Immunology 2024Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE...
BACKGROUND
Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks.
METHODS
Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured.
RESULTS
Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for D-dimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 baseline) and D-dimer in 71% (p=0.001 . baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema.
CONCLUSION
The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE.
Topics: Humans; Female; Male; Adult; Angioedemas, Hereditary; Middle Aged; Biomarkers; Aged; Inflammation; Adolescent; Child; Young Adult; Aged, 80 and over; Complement C1 Inhibitor Protein; Serum Amyloid A Protein; Factor XII; Blood Sedimentation; Inflammation Mediators; Fibrin Fibrinogen Degradation Products
PubMed: 38953032
DOI: 10.3389/fimmu.2024.1400526 -
Frontiers in Immunology 2024Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute...
INTRODUCTION
Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF).
METHODS
Serum and BALF from healthy horses (HE, = 18) and horses with mild-moderate asthma (MEA, = 20) or severe asthma (SEA, = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens ( lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidyl-peptidase 5, class II aldolase/adducin domain protein, glucoamylase, beta-hexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by bead-based assays.
RESULTS
MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti- binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig.
DISCUSSION
immunogenicity was confirmed without identification of single dominant antigens here. provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis.
Topics: Animals; Horses; Aspergillus fumigatus; Bronchoalveolar Lavage Fluid; Asthma; Immunoglobulin G; Immunoglobulin A; Horse Diseases; Antigens, Fungal; Male; Neutrophils; Female; Immunoglobulin E; Antibodies, Fungal
PubMed: 38953030
DOI: 10.3389/fimmu.2024.1406794 -
Frontiers in Immunology 2024Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of... (Review)
Review
BACKGROUND AND OBJECTIVES
Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of anti-GlyR antibody-related disease.
METHODS
By collecting clinical information from admitted patients positive for glycine receptor (GlyR) antibody, the clinical characteristics of a new patient positive for GlyR antibody were reported in this study. To obtain additional information regarding anti-GlyR antibody-linked illness, clinical data and findings on both newly reported instances in this study and previously published cases were merged and analyzed.
RESULTS
A new case of anti-GlyR antibody-related progressive encephalomyelitis with rigidity and myoclonus (PERM) was identified in this study. A 20-year-old man with only positive cerebrospinal fluid anti-GlyR antibody had a good prognosis with first-line immunotherapy. The literature review indicated that the common clinical manifestations of anti-GlyR antibody-related disease included PERM or stiff-person syndrome (SPS) (n = 179, 50.1%), epileptic seizure (n = 94, 26.3%), and other neurological disorders (n = 84, 24.5%). Other neurological issues included demyelination, inflammation, cerebellar ataxia and movement disorders, encephalitis, acute psychosis, cognitive impairment or dementia, celiac disease, Parkinson's disease, neuropathic pain and allodynia, steroid-responsive deafness, hemiballism/tics, laryngeal dystonia, and generalized weakness included respiratory muscles. The group of PERM/SPS exhibited a better response to immunotherapy than others.
CONCLUSIONS
The findings suggest the presence of multiple clinical phenotypes in anti-GlyR antibody-related disease. Common clinical phenotypes include PERM, SPS, epileptic seizure, and paraneoplastic disease. Patients with RERM/SPS respond well to immunotherapy.
Topics: Humans; Male; Receptors, Glycine; Autoantibodies; Young Adult; Encephalomyelitis; Muscle Rigidity; Myoclonus; Stiff-Person Syndrome; Adult
PubMed: 38953026
DOI: 10.3389/fimmu.2024.1387591