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European Journal of Case Reports in... 2024Small cell lung cancer is an aggressive tumor with a poor prognosis that requires prompt treatment. While radiotherapy may enhance survival when superior vena cava...
BACKGROUND
Small cell lung cancer is an aggressive tumor with a poor prognosis that requires prompt treatment. While radiotherapy may enhance survival when superior vena cava syndrome is present, radiation therapy-induced pericardial disease can be a potential complication.
CASE REPORT
A 55-year-old man, who recently underwent radiotherapy for stage IV small-cell lung cancer complicated by superior vena cava syndrome, presented with chest pain and dyspnea. In the emergency room, he was dyspneic, hypotensive, and tachycardic. Pulmonary auscultation revealed the absence of lung sounds on the right. The initial electrocardiogram showed ST-segment elevation in lateral leads and in lead DII, with reciprocal changes in lead DIII. A bedside transthoracic echocardiogram revealed cardiac tamponade and emergent pericardiocentesis was performed, removing 500 ml of purulent fluid, resulting in an immediate clinical improvement. Thoracentesis was also performed, showing no empyema. Large spectrum empirical antibiotic therapy was started. Cultures from the pericardial fluid and peripheral blood grew multi-sensitive . Cytological analysis of the pericardial fluid was consistent with infection. The patient improved after 2 weeks of targeted antibiotic therapy and underwent the first cycle of chemotherapy. He was discharged with an early scheduled pulmonology appointment.
CONCLUSIONS
Although the most common causes of pericardial effusion in lung cancer are malignant, non-malignant etiologies should also be considered. This patient had an infectious pericardial effusion most probably due to a pericardial-mediastinal mass fistula caused by radiotherapy. This was a diagnostic challenge, both in the emergency room as well in the inpatient setting.
LEARNING POINTS
Small cell lung cancer is a fast-growing cancer that exhibits aggressive behavior.In patients with lung cancer, malignant pericardial effusions are more common than non-malignant ones.Purulent pericardial effusions, especially those due to lung cancer, are rare in developed countries with very few reports in the literature.
PubMed: 38846671
DOI: 10.12890/2024_004477 -
Vaccine Jun 2024To evaluate the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) compared to 13-valent pneumococcal conjugate vaccine (PCV13) for the pediatric...
OBJECTIVES
To evaluate the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) compared to 13-valent pneumococcal conjugate vaccine (PCV13) for the pediatric population in Korea, where the four-dose vaccine coverage rate is over 97%.
METHODS
We constructed a Markov model to calculate the cost and quality-adjusted life-years (QALYs) over 10 years. The health states were susceptible states; disease states, which included invasive pneumococcal diseases such as meningitis, bacteremia, pneumonia, and acute otitis media; and death attributable to pneumococcal disease. The annual incidence and mortality due to pneumococcal diseases were estimated based on the serotypes covered by PCV13 and PCV20, vaccine coverage rate, vaccine effectiveness, and population size. Vaccine, administration, and disease costs were included in the model.
RESULTS
In the total population (n = 51,431,305), PCV20 prevented more pneumococcal diseases and deaths, resulting in a gain of 74,855 QALY over PCV13. Meanwhile, the PCV20 group spent $275,136,631 less than the PCV13 group. As PCV20 gained more QALYs but spent less on total medical costs than PCV13, PCV20 was dominant over PCV13.
CONCLUSIONS
In the Korean population, PCV20 is a cost-effective and dominant option over PCV13. Our findings provide evidence for decision-making regarding the introduction of PCV20 in countries with high vaccine coverage.
PubMed: 38845302
DOI: 10.1016/j.vaccine.2024.05.048 -
PLoS Genetics Jun 2024Evaluation of the apportionment of genetic diversity of human bacterial commensals within and between human populations is an important step in the characterization of...
Evaluation of the apportionment of genetic diversity of human bacterial commensals within and between human populations is an important step in the characterization of their evolutionary potential. Recent studies showed a correlation between the genomic diversity of human commensal strains and that of their host, but the strength of this correlation and of the geographic structure among human populations is a matter of debate. Here, we studied the genomic diversity and evolution of the phylogenetically related oro-nasopharyngeal healthy-carriage Streptococcus mitis and Streptococcus pneumoniae, whose lifestyles range from stricter commensalism to high pathogenic potential. A total of 119 S. mitis genomes showed higher within- and among-host variation than 810 S. pneumoniae genomes in European, East Asian and African populations. Summary statistics of the site-frequency spectrum for synonymous and non-synonymous variation and ABC modelling showed this difference to be due to higher ancestral bacterial population effective size (Ne) in S. mitis, whose genomic variation has been maintained close to mutation-drift equilibrium across (at least many) generations, whereas S. pneumoniae has been expanding from a smaller ancestral bacterial population. Strikingly, both species show limited differentiation among human populations. As genetic differentiation is inversely proportional to the product of effective population size and migration rate (Nem), we argue that large Ne have led to similar differentiation patterns, even if m is very low for S. mitis. We conclude that more diversity within than among human populations and limited population differentiation must be common features of the human microbiome due to large Ne.
Topics: Streptococcus mitis; Humans; Streptococcus pneumoniae; Genetic Variation; Evolution, Molecular; Genome, Bacterial; Phylogeny; Genetics, Population
PubMed: 38843312
DOI: 10.1371/journal.pgen.1011317 -
Frontiers in Medicine 2024Invasive Pneumococcal Disease (IPD) causes significant morbidity and mortality in children under 5 y. Colombia introduced PCV10 vaccination in 2012, and the...
Serotype distribution, clinical characteristics, and antimicrobial resistance of pediatric invasive pneumococcal disease in Colombia during PCV10 mass vaccination (2017-2022).
INTRODUCTION
Invasive Pneumococcal Disease (IPD) causes significant morbidity and mortality in children under 5 y. Colombia introduced PCV10 vaccination in 2012, and the Neumocolombia network has been monitoring IPD in pediatric patients since 2008.
MATERIALS AND METHODS
This study is a secondary analysis of a prospective cohort involving pediatric patients with IPD admitted to 17 hospitals in Colombia, from January 1st, 2017, to December 31st, 2022. We present data on serotypes (Spn), clinical characteristics, and resistance patterns.
RESULTS
We report 530 patients, 215 (40.5%) were younger than 24 months. Among these, 344 cases (64.7%) presented with pneumonia, 95 (17.9%) with primary bacteremia, 53 (10%) with meningitis, 6 (1.1%) had pneumonia and meningitis, and 32 (6%) had other IPD diagnosis. The median hospital stay was 12 days (RIQ 8-14 days), and 268 (50.6%) were admitted to the ICU, of whom 60 (11.3%) died. Serotyping was performed in 298 (56.1%). The most frequent serotypes were Spn19A (51.3%), Spn6C (7.7%), Spn3 (6.7%), Spn6A (3.6%), and Spn14 (3.6%). Of 495 (93%) isolates with known susceptibility, 46 (9.2%) were meningeal (M) and 449 (90.7%) non-meningeal (NM). Among M isolates, 41.3% showed resistance to penicillin, and 21.7% decreased susceptibility to ceftriaxone. For NM isolates, 28.2% had decreased susceptibility to penicilin, and 24.2% decreased susceptibility to ceftriaxone. Spn19A showed the highest resistant to penicillin at 47% and was linked to multiresistance.
CONCLUSION
The prevalence of PCV10-included serotypes decreased, while serotypes 19A and 6C increased, with Spn19A being associated with multiresistance. These findings had played a crucial role in the decision made by Colombia to modify its immunization schedule by switching to PCV13 in July 2022.
PubMed: 38841583
DOI: 10.3389/fmed.2024.1380125 -
Frontiers in Immunology 2024The disaccharide (β-D-glucopyranosyluronic acid)-(1→4)-β-D-glucopyranoside represents a repeating unit of the capsular polysaccharide of serotype 3. A conjugate of...
The disaccharide (β-D-glucopyranosyluronic acid)-(1→4)-β-D-glucopyranoside represents a repeating unit of the capsular polysaccharide of serotype 3. A conjugate of the disaccharide with BSA (di-BSA conjugate) adjuvanted with aluminum hydroxide induced - in contrast to the non-adjuvanted conjugate - IgG1 antibody production and protected mice against serotype 3 infection after intraperitoneal prime-boost immunization. Adjuvanted and non-adjuvanted conjugates induced production of Th1 (IFNγ, TNFα); Th2 (IL-5, IL-13); Th17 (IL-17A), Th1/Th17 (IL-22), and Th2/Th17 cytokines (IL-21) after immunization. The concentration of cytokines in mice sera was higher in response to the adjuvanted conjugate, with the highest level of IL-17A production after the prime and boost immunizations. In contrast, the non-adjuvanted conjugate elicited only weak production of IL-17A, which gradually decreased after the second immunization. After boost immunization of mice with the adjuvanted di-BSA conjugate, there was a significant increase in the number of CD45+/CD19+ B cells, TCR+ γδ T cell, CD5+ В1 cells, and activated cells with MHC II+ expression in the spleens of the mice. IL-17A, TCR+ γδ T cells, and CD5+ В1 cells play a crucial role in preventing pneumococcal infection, but can also contribute to autoimmune diseases. Immunization with the adjuvanted and non-adjuvanted di-BSA conjugate did not elicit autoantibodies against double-stranded DNA targeting cell nuclei in mice. Thus, the molecular and cellular markers associated with antibody production and protective activity in response to immunization with the di-BSA conjugate adjuvanted with aluminum hydroxide are IL-17A, TCR+ γδ T cells, and CD5+ В1 cells against the background of increasing MHC II+ expression.
Topics: Animals; Interleukin-17; Streptococcus pneumoniae; Mice; Serum Albumin, Bovine; Pneumococcal Vaccines; Pneumococcal Infections; Disaccharides; Bacterial Capsules; Polysaccharides, Bacterial; Adjuvants, Immunologic; Female; Antibodies, Bacterial; Intraepithelial Lymphocytes; Serogroup; Receptors, Antigen, T-Cell, gamma-delta
PubMed: 38840926
DOI: 10.3389/fimmu.2024.1388721 -
Immunity & Ageing : I & A Jun 2024Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia in older adults. Successful control of pneumococci requires robust pulmonary neutrophil influx...
BACKGROUND
Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia in older adults. Successful control of pneumococci requires robust pulmonary neutrophil influx early in infection. However, aging is associated with aberrant neutrophil recruitment and the mechanisms behind that are not understood. Here we explored how neutrophil recruitment following pneumococcal infection changes with age and the host pathways regulating this.
RESULTS
Following pneumococcal infection there was a significant delay in early neutrophil recruitment to the lungs of aged mice. Neutrophils from aged mice showed defects in trans-endothelial migration in vitro compared to young controls. To understand the pathways involved, we examined immune modulatory extracellular adenosine (EAD) signaling, that is activated upon cellular damage. Signaling through the lower affinity A2A and A2B adenosine receptors had no effect on neutrophil recruitment to infected lungs. In contrast, inhibition of the high affinity A1 receptor in young mice blunted neutrophil recruitment to the lungs following infection. A1 receptor inhibition decreased expression of CXCR2 on circulating neutrophils, which is required for trans-endothelial migration. Indeed, A1 receptor signaling on neutrophils was required for their ability to migrate across endothelial cells in response to infection. Aging was not associated with defects in EAD production or receptor expression on neutrophils. However, agonism of A1 receptor in aged mice rescued the early defect in neutrophil migration to the lungs and improved control of bacterial burden.
CONCLUSIONS
This study suggests age-driven defects in EAD damage signaling can be targeted to rescue the delay in pulmonary neutrophil migration in response to bacterial pneumonia.
PubMed: 38840213
DOI: 10.1186/s12979-024-00442-3 -
PLoS Pathogens Jun 2024ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy...
ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiont Streptococcus pneumoniae (pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids. The system comprises five exposed Oligopeptide Binding Proteins (OBPs) and four proteins building the ABC transporter channel. Here, we present a structural analysis of all the OBPs in this system. Multiple crystallographic structures, capturing both open and closed conformations along with complexes involving chemically synthesized peptides, have been solved at high resolution providing insights into the molecular basis of their diverse peptide specificities. Mass spectrometry analysis of oligopeptides demonstrates the unexpected remarkable promiscuity of some of these proteins when expressed in Escherichia coli, displaying affinity for a wide range of peptides. Finally, a model is proposed for the complete Ami transport system in complex with its various OBPs. We further disclosed, through in silico modelling, some essential structural changes facilitating oligopeptide transport into the cellular cytoplasm. Thus, the structural analysis of the Ami system provides valuable insights into the mechanism and specificity of oligopeptide binding by the different OBPs, shedding light on the intricacies of the uptake mechanism and the in vivo implications for this human pathogen.
Topics: Streptococcus pneumoniae; Bacterial Proteins; Oligopeptides; ATP-Binding Cassette Transporters; Crystallography, X-Ray; Models, Molecular; Lipoproteins
PubMed: 38838057
DOI: 10.1371/journal.ppat.1011883 -
JAC-antimicrobial Resistance Jun 2024Ceftriaxone is administered in regimens of either 2 g once-daily or 1 g twice-daily for the treatment of pneumonia caused by . Previous clinical study suggests the...
BACKGROUND
Ceftriaxone is administered in regimens of either 2 g once-daily or 1 g twice-daily for the treatment of pneumonia caused by . Previous clinical study suggests the 2 g once-daily regimen is more effective, but comparison of antimicrobial efficacy between are lacking.
OBJECTIVES
To assess the antimicrobial efficacy of these two ceftriaxone regimens against using a murine model of pneumonia.
METHODS
The study employed three isolates with ceftriaxone MICs of 1, 2 and 4 mg/L and two human-simulated regimens based on the blood concentration of ceftriaxone (1 g twice-daily and 2 g once-daily). Antimicrobial activity was quantified based on the change in bacterial counts (Δlog cfu/lungs) observed in treated mice after 24 h, relative to the control mice at 0 h.
RESULTS
The human-simulated 2 g once-daily regimen of ceftriaxone exhibited significantly higher antimicrobial activity against isolates with MICs of 1 and 2 mg/L compared with the 1 g twice-daily regimen (1 mg/L, -5.14 ± 0.19 Δlog cfu/lungs versus -3.47 ± 0.17 Δlog cfu/lungs, < 0.001; 2 mg/L, -3.41 ± 0.31 Δ log cfu/lungs versus -2.71 ± 0.37 Δlog cfu/lungs, = 0.027). No significant difference in antimicrobial activity was observed against the isolate with a MIC of 4 mg/L between the two regimens (-0.33 ± 0.18 Δlog cfu/lungs versus -0.42 ± 0.37 Δlog cfu/lungs, = 0.684).
CONCLUSION
2 g once-daily regimen of ceftriaxone is more effective for treating pneumonia caused by with MICs of ≤2 mg/L.
PubMed: 38836196
DOI: 10.1093/jacamr/dlae092 -
Canada Communicable Disease Report =... May 2024Invasive pneumococcal disease (IPD, ) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution...
BACKGROUND
Invasive pneumococcal disease (IPD, ) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022.
METHODS
The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System.
RESULTS
The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, <0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, <0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, <0.05).
CONCLUSION
The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.
PubMed: 38835503
DOI: 10.14745/ccdr.v50i05a02 -
Scientific Reports Jun 2024Sudden aggravations of chronic inflammatory airway diseases are difficult-to-foresee life-threatening episodes for which advanced prognosis-systems are highly desirable....
Sudden aggravations of chronic inflammatory airway diseases are difficult-to-foresee life-threatening episodes for which advanced prognosis-systems are highly desirable. Here we present an experimental chip-based fluidic system designed for the rapid and sensitive measurement of biomarkers prognostic for potentially imminent asthma or COPD exacerbations. As model biomarkers we chose three cytokines (interleukin-6, interleukin-8, tumor necrosis factor alpha), the bacterial infection marker C-reactive protein and the bacterial pathogen Streptococcus pneumoniae-all relevant factors in exacerbation episodes. Assay protocols established in laboratory environments were adapted to 3D-printed fluidic devices with emphasis on short processing times, low reagent consumption and a low limit of detection in order to enable the fluidic system to be used in point-of-care settings. The final device demonstrator was validated with patient sample material for its capability to detect endogenous as well as exogenous biomarkers in parallel.
Topics: Biomarkers; Humans; Point-of-Care Systems; Pulmonary Disease, Chronic Obstructive; Streptococcus pneumoniae; C-Reactive Protein; Cytokines; Asthma; Lab-On-A-Chip Devices; Interleukin-6; Prognosis; Tumor Necrosis Factor-alpha
PubMed: 38834656
DOI: 10.1038/s41598-024-62784-8