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Pulmonary Medicine 2024Bilothorax is defined as the presence of bile in the pleural space. It is a rare condition, and diagnosis is confirmed with a pleural fluid-to-serum bilirubin ratio of...
BACKGROUND
Bilothorax is defined as the presence of bile in the pleural space. It is a rare condition, and diagnosis is confirmed with a pleural fluid-to-serum bilirubin ratio of >1.
METHODS
The PubMed, Embase, Google Scholar, and CINAHL databases were searched using predetermined Boolean parameters. The systematic literature review was done per PRISMA guidelines. Retrospective studies, case series, case reports, and conference abstracts were included. The patients with reported pleural fluid analyses were pooled for fluid parameter data analysis.
RESULTS
Of 838 articles identified through the inclusion criteria and removing 105 duplicates, 732 articles were screened with abstracts, and 285 were screened for full article review. After this, 123 studies qualified for further detailed review, and of these, 115 were pooled for data analysis. The mean pleural fluid and serum bilirubin levels were 72 mg/dL and 61 mg/dL, respectively, with a mean pleural fluid-to-serum bilirubin ratio of 3.47. In most cases, the bilothorax was reported as a subacute or remote complication of hepatobiliary surgery or procedure, and traumatic injury to the chest or abdomen was the second most common cause. Tube thoracostomy was the main treatment modality (73.83%), followed by serial thoracentesis. Fifty-two patients (51.30%) had associated bronchopleural fistulas. The mortality was considerable, with 18/115 (15.65%) reported death. Most of the patients with mortality had advanced hepatobiliary cancer and were noted to die of complications not related to bilothorax.
CONCLUSION
Bilothorax should be suspected in patients presenting with pleural effusion following surgical manipulation of hepatobiliary structures or a traumatic injury to the chest. This review is registered with CRD42023438426.
Topics: Female; Humans; Bile; Bilirubin; Pleural Effusion; Thoracentesis; Thoracostomy; Aged
PubMed: 38947176
DOI: 10.1155/2024/3973056 -
Frontiers in Cellular and Infection... 2024Convergence of (KP) pathotypes has been increasingly reported in recent years. These pathogens combine features of both multidrug-resistant and hypervirulent KP....
BACKGROUND
Convergence of (KP) pathotypes has been increasingly reported in recent years. These pathogens combine features of both multidrug-resistant and hypervirulent KP. However, clinically used indicators for hypervirulent KP identification, such as hypermucoviscosity, appear to be differentially expressed in convergent KP, potential outbreak clones are difficult to identify. We aimed to fill such knowledge gaps by investigating the temperature dependence of hypermucoviscosity and virulence in a convergent KP strain isolated during a clonal outbreak and belonging to the high-risk sequence type (ST)307.
METHODS
Hypermucoviscosity, biofilm formation, and mortality rates in larvae were examined at different temperatures (room temperature, 28°C, 37°C, 40°C and 42°C) and with various phenotypic experiments including electron microscopy. The underlying mechanisms of the phenotypic changes were explored via qPCR analysis to evaluate plasmid copy numbers, and transcriptomics.
RESULTS
Our results show a temperature-dependent switch above 37°C towards a hypermucoviscous phenotype, consistent with increased biofilm formation and mortality, possibly reflecting a bacterial response to fever-like conditions. Furthermore, we observed an increase in plasmid copy number for a hybrid plasmid harboring carbapenemase and genes. However, transcriptomic analysis revealed no changes in expression at higher temperatures, suggesting alternative regulatory pathways.
CONCLUSION
This study not only elucidates the impact of elevated temperatures on hypermucoviscosity and virulence in convergent KP but also sheds light on previously unrecognized aspects of its adaptive behavior, underscoring its resilience to changing environments.
Topics: Klebsiella pneumoniae; Biofilms; Virulence; Animals; Klebsiella Infections; Temperature; Larva; Plasmids; Moths; Humans; Virulence Factors; Bacterial Proteins; Lepidoptera; Viscosity; Phenotype; Gene Expression Profiling
PubMed: 38947124
DOI: 10.3389/fcimb.2024.1411286 -
Research Square Jun 2024Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired...
Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the number of hours alive and free of the use of vancomycin within the first seven days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. This trial was registered on ClinicalTrials.gov on February 22, 2024. (ClinicalTrials.gov identifier: NCT06272994).
PubMed: 38947088
DOI: 10.21203/rs.3.rs-4365928/v1 -
MedRxiv : the Preprint Server For... Jun 2024Aging populations in rural areas of low and middle-income countries will increasingly need care. However, formal support is severely limited and adult children are...
OBJECTIVES
Aging populations in rural areas of low and middle-income countries will increasingly need care. However, formal support is severely limited and adult children are frequently unavailable due to morbidity, early mortality, employment and migration. We aimed to describe how care is shared within and between households for older adults in a rural South African setting.
METHODS
We conducted quantitative interviews with 1012 household members and non-household caregivers of 106 older adults living with or at risk of cognitive decline in rural Mpumalanga, South Africa. Using descriptive statistics and regression analysis, we described how care is shared, with particular attention to generational patterns of care.
RESULTS
Informal care for older persons was spread among family, friends, and neighbours, with minimal paid support. This care was mostly provided by female relatives one or two generations younger than the recipient, and unemployed. However, a smaller number of paid caregivers, also mostly female, provided the most intensive care. Spouses commonly took on the role of primary caregiver for their partner.
DISCUSSION
In our study, care mainly came from household members due to close family ties and practical considerations, with support from outside the household. This reflects shared history, reciprocal relationships, and easy access to care tasks within the household. A deeper understanding of how informal care for older adults is shared in low- and middle-income countries is essential for developing targeted interventions.
PubMed: 38947086
DOI: 10.1101/2024.06.20.24309077 -
MedRxiv : the Preprint Server For... Jun 2024Despite the availability of HPV vaccines for over a decade, coverage across the United States (US) is varied. While some states have made concerted efforts to increase...
BACKGROUND
Despite the availability of HPV vaccines for over a decade, coverage across the United States (US) is varied. While some states have made concerted efforts to increase HPV vaccination coverage, most model-based analyses have estimated vaccine impact on the US. We estimated the impact of hypothetical changes in HPV vaccination coverage at the state level for three states with varying levels of HPV vaccination coverage and cervical cancer incidence (California, New York, Texas) using a mathematical model.
METHODS
We developed a new mathematical model of HPV transmission and cervical cancer tailored to state-level cancer incidence and mortality. We quantified the public health impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 and the effect on time to elimination in the three states.
RESULTS
Increasing vaccination coverage to 80% in Texas in 10 years could reduce cervical cancer incidence by 50.9% (95%-CrI: 46.6-56.1%) by 2100. In New York and California, achieving the same coverage could reduce incidence by 27.3% (95%-CrI: 23.9-31.5%) and 24.4% (95%-CrI: 20.0-30.0%), respectively. Achieving 80% coverage in 5 years will slightly increase the reduction. If 2019 vaccination coverage continues, cervical cancer elimination would be reached in the US by 2051 (95%-Crl: 2034-2064). However, the timeline by which individual states reach elimination could vary by decades.
CONCLUSION
Achieving an HPV vaccination coverage target of 80% by 2030 will benefit states with low vaccination coverage and high cervical cancer incidence the most. Our results highlight the value of more geographically focused analyses to inform priorities.
PubMed: 38947042
DOI: 10.1101/2024.06.11.24308795 -
MedRxiv : the Preprint Server For... Jun 2024Intermittent preventive treatment for malaria in pregnancy (IPTp) can improve birth outcomes, but whether it confers benefits to postnatal growth is unclear. We...
BACKGROUND
Intermittent preventive treatment for malaria in pregnancy (IPTp) can improve birth outcomes, but whether it confers benefits to postnatal growth is unclear. We investigated the effect of IPTp on infant growth in Uganda and its pathways of effects using causal mediation analyses.
METHODS
We analyzed data from 633 infants born to mothers enrolled in a randomized trial of monthly IPTp with dihydroartemisinin-piperaquine (DP) vs sulfadoxine-pyrimethamine (SP) (NCT02793622). Weight and length were measured from 0-12 months of age. Using generalized linear models, we estimated effects of DP vs. SP on gravidity-stratified mean length-for-age (LAZ) and weight-for-length Z-scores (WLZ). We investigated mediation by placental malaria, gestational weight change, maternal anemia, maternal inflammation-related proteins, preterm birth, birth length, and birth weight. Mediation models adjusted for infant sex, gravidity, gestational age at enrollment, maternal age, maternal parasitemia at enrollment, education, and wealth.
FINDINGS
SP increased LAZ by 0.18-0.28 Z from birth through age 4 months compared to DP, while DP increased WLZ by 0.11-0.28 Z from 2-8 months compared to SP among infants of multigravidae. We did not observe these differences among primigravida. Mediators of SP included increased birth weight and length and maternal stem cell factor at delivery. Mediators of DP included placental malaria and birth length, maternal IL-18, CDCP1, and CD6 at delivery.
INTERPRETATION
In high malaria transmission settings, different IPTp regimens influenced infant growth among multigravidae through distinct pathways in the period of exclusive breastfeeding, when few other interventions are available.
FUNDING
Stanford Center for Innovation and Global Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation.
RESEARCH IN CONTEXT
Intermittent Preventive Treatment in Pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the WHO for regions with moderate-to-high malaria transmission. While SP is effective in reducing neonatal mortality and low birth weight, its efficacy has diminished in some areas of sub-Saharan Africa due to widespread parasite resistance to SP. Although IPTp with dihydroartemisinin-piperaquine (IPTp-DP) has demonstrated superior efficacy in reducing malaria in pregnancy, its impact on birth outcomes has not significantly surpassed that of SP. The ultimate goal of IPTp extends beyond enhancing birth outcomes to include benefits during infancy and later stages. Yet, the effects of SP vs. DP in relation to infant growth post-birth and the underlying mechanisms remain unknown. Prior studies also found that different IPTp regimens worked through different pathways, with DP influencing birth outcomes by reducing placental malaria and SP influencing them through non-malarial pathways such as maternal weight gain. Here, we re-analyzed data from of a randomized trial in Uganda to explore the impacts of these two IPTp regimens on infant growth and to understand potential mechanisms underlying its impacts on infant growth. This study quantified how IPTp with SP compared to DP influenced infants' growth trajectories, both ponderal and linear, during the first year of life. We found that SP improved linear growth of infants up to age 4 months compared to DP, and DP improved ponderal growth of infants from 2-8 months compared to SP among babies who were born to multigravidae. In addition, we identified birth size, placental malaria, and certain markers of maternal inflammation measured at delivery using the Olink Target 96 inflammation panel as pathways through which IPTp influenced infant growth. Our approach provides new insights into effects of IPTp beyond birth and the mechanisms by which IPTp impacts infant growth. Our study provides evidence that different IPTp regimens can influence infant postnatal growth through distinct pathways. Our findings highlight the potential of combined SP and DP IPTp regimens and bolster the evidence base for continued delivery of IPTp to improve maternal and child health outcomes, particularly in malaria-endemic regions.
PubMed: 38947035
DOI: 10.1101/2024.06.09.24308656 -
Research Square Jun 2024Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model.
OBJECTIVE AND DESIGN
Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model.
TREATMENT
Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 mg/kg/day, i.p.) at day 3 post-infection. Methods Mortality rate was assessed up to day 21 and inflammatory parameters were assessed at days 5 and 7. Results AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in FPR2/3 animals. In mice treated with LXA (50mg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of anti-inflammatory T cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice. Conclusions Therefore, treatment with a lipoxin A analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.
PubMed: 38947034
DOI: 10.21203/rs.3.rs-4491036/v1 -
MedRxiv : the Preprint Server For... Jun 2024Triglyceride (TG)/High density lipoprotein cholesterol (HDL-C) ratio (THR) represents a single surrogate predictor of hyperinsulinemia or insulin resistance that is...
Novel Loci ( ) for Triglyceride / High-density Lipoprotein Cholesterol Ratio Longitudinal Change (ΔTHR) among Subjects without Type 2 Diabetes: Evidence from the Long Life Family Study (LLFS) and the Framingham Heart Study (FHS) Offspring Cohort (OS).
AIMS/HYPOTHESIS
Triglyceride (TG)/High density lipoprotein cholesterol (HDL-C) ratio (THR) represents a single surrogate predictor of hyperinsulinemia or insulin resistance that is associated with premature aging processes, risk of diabetes and increased mortality. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among subjects of European ancestry who had complete data from two exams collected about seven years apart from the Long Life Family Study (LLFS, n=1384), a study with familial clustering of exceptional longevity in the US and Denmark.
METHODS
Subjects with diabetes or using medications for dyslipidemia were excluded from this analysis. ΔTHR was derived using growth curve modeling, and adjusted for age, sex, field centers, and principal components (PCs). GWAS was conducted using a linear mixed model accounted for familial relatedness. Our linkage scan was built on haplotype-based IBD estimation with 0.5 cM average spacing.
RESULTS
Heritability of ΔTHR was moderate (46%). Our GWAS identified a significant locus at the ( =1.58e-9) for ΔTHR; this gene locus has been reported before influencing baseline THR levels. Our GWLS found evidence for a significant linkage with a logarithm of the odds (LODs) exceeding 3 on (LODs=4.1). Using a subset of 25 linkage enriched families (pedigree-specific LODs>0.1), we assessed sequence elements under and identified two novel variants ( -rs114108468, =5e-6, MAF=1.8%; -rs16864075, =3e-6, MAF=8%; accounted for ∼28% and ∼29% of the linkage, respectively, and 57% jointly). While the former variant was associated with ( =7e-5) / ( =3.49e-2) RNA transcriptional levels, the latter variant was not associated with ( =0.23) RNA transcriptional levels. Replication in FHS OS observed modest effect of these loci on ΔTHR. Of 188 metabolites from 13 compound classes assayed in LLFS, we observed multiple metabolites (e.g., DG.38.5, PE.36.4, TG.58.3) that were significantly associated with the variants ( <3e-4).
CONCLUSIONS
Our linkage-guided sequence analysis approach permitted our discovery of two novel gene variants -rs114108468 and -rs16864075 on for ΔTHR among subjects without diabetes selected for exceptional survival and healthy aging.
PubMed: 38947029
DOI: 10.1101/2024.06.18.24309120 -
MedRxiv : the Preprint Server For... Jun 2024Few studies have evaluated baseline predictors of clinical outcomes among people with HIV starting antiretroviral therapy (ART) in the modern era of rapid ART initiation.
INTRODUCTION
Few studies have evaluated baseline predictors of clinical outcomes among people with HIV starting antiretroviral therapy (ART) in the modern era of rapid ART initiation.
METHODS
We conducted a secondary analysis of a randomized controlled trial of two rapid treatment initiation strategies for people with treatment-naïve HIV and tuberculosis symptoms at an urban clinic in Haiti. We used logistic regression models to assess associations between baseline characteristics and (1) retention in care at 48 weeks, (2) HIV viral load suppression at 48 weeks (among participants who underwent viral load testing), and (3) all-cause mortality.
RESULTS
500 participants were enrolled in the study 11/2017-1/2020. Eighty-eight (18%) participants were diagnosed with tuberculosis, and ART was started in 494 (99%). After adjustment, less than secondary education (adjusted odds ratio [AOR] 0.21, 95% CI 0.10-0.46), dolutegravir initiation (AOR 2.57, 95% CI 1.22-5.43), age (AOR 1.42 per 10-year increase, 95% CI 1.01-1.99), and tuberculosis diagnosis (AOR 3.92, 95% CI 1.36-11.28) were significantly associated with retention. Age (AOR 1.36, 95% CI 1.05-1.75), dolutegravir initiation (AOR 1.75, 95% CI 1.07-2.85), and tuberculosis diagnosis (AOR 0.50, 95% CI 0.28-0.89) were associated with viral suppression. Higher CD4 cell count at enrollment (unadjusted odds ratio [OR] 0.69, 95% CI 0.55-0.87) and anemia (OR 4.86, 95% CI 1.71-13.81) were associated with mortality.
CONCLUSIONS
We identified sociodemographic, treatment-related, clinical, and laboratory-based predictors of clinical outcomes. These characteristics may serve as markers of sub- populations that could benefit from additional interventions to support treatment success after rapid treatment initiation.
PubMed: 38946994
DOI: 10.1101/2024.06.19.24309189 -
MedRxiv : the Preprint Server For... Jun 2024Sepsis is the leading cause of death of hospitalized children worldwide. Despite the established link between immune dysregulation and mortality in pediatric sepsis, it...
Sepsis is the leading cause of death of hospitalized children worldwide. Despite the established link between immune dysregulation and mortality in pediatric sepsis, it remains unclear which host immune factors contribute causally to adverse sepsis outcomes. Identifying modifiable pathobiology is an essential first step to successful translation of biologic insights into precision therapeutics. We designed a prospective, longitudinal cohort study of 88 critically ill pediatric patients with multiple organ dysfunction syndrome (MODS), including patients with and without sepsis, to define subphenotypes associated with targetable mechanisms of immune dysregulation. We first assessed plasma proteomic profiles and identified shared features of immune dysregulation in MODS patients with and without sepsis. We then employed consensus clustering to define three subphenotypes based on protein expression at disease onset and identified a strong association between subphenotype and clinical outcome. We next identified differences in immune cell frequency and activation state by MODS subphenotype and determined the association between hyperinflammatory pathway activation and cellular immunophenotype. Using single cell transcriptomics, we demonstrated STAT3 hyperactivation in lymphocytes from the sickest MODS subgroup and then identified an association between STAT3 hyperactivation and T cell immunometabolic dysregulation. Finally, we compared proteomics findings between patients with MODS and patients with inborn errors of immunity that amplify cytokine signaling pathways to further assess the impact of STAT3 hyperactivation in the most severe patients with MODS. Overall, these results identify a potentially pathologic and targetable role for STAT3 hyperactivation in a subset of pediatric patients with MODS who have high severity of illness and poor prognosis.
PubMed: 38946991
DOI: 10.1101/2024.06.11.24308709