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Cureus May 2024Infective endocarditis (IE) is a severe infection of the endocardium, frequently involving heart valves, and is associated with significant morbidity and mortality. At... (Review)
Review
Infective endocarditis (IE) is a severe infection of the endocardium, frequently involving heart valves, and is associated with significant morbidity and mortality. At the same time, traditional complications of IE, such as valvular dysfunction and embolic events, are well-documented, and uncommon cardiac manifestations, such as chorda tendinea rupture and pulmonary valve vegetation, present unique diagnostic and management challenges. This comprehensive review explores the pathophysiology, clinical presentation, diagnostic strategies, and management approaches for IE's chorda tendinea rupture and pulmonary valve vegetation. Through a detailed examination of the literature and discussion of clinical scenarios, we highlight the importance of recognizing these rare complications and discuss the implications for clinical practice. Additionally, we identify knowledge gaps and propose areas for future research to enhance further our understanding and management of these unusual cardiac complications in IE. This review aims to provide clinicians with valuable insights to improve patient care and outcomes in the challenging setting of infective endocarditis.
PubMed: 38947598
DOI: 10.7759/cureus.61401 -
Clinical Case Reports Jul 2024In patients with poorly controlled diabetes, early recognition of rare fungal infections like pulmonary mucormycosis, especially when presenting with unusual...
KEY CLINICAL MESSAGE
In patients with poorly controlled diabetes, early recognition of rare fungal infections like pulmonary mucormycosis, especially when presenting with unusual complications such as broncho-esophageal fistula, is critical. Prompt intervention with antifungal therapy and consideration for surgical debridement significantly impact outcomes. Multidisciplinary management is paramount for such complex cases.
ABSTRACT
Mucormycosis is a rare fungal infection caused by the Mucorales. This infection is mostly observed among those with poorly controlled diabetes or immunodeficiency. The most common presentation of the infection among those with poorly controlled diabetes is rhino-orbit-cerebral involvement. In this case report, we provide the history and outcome of a rare case of pulmonary mucormycosis in a patient with poorly controlled diabetes who was simultaneously diagnosed with broncho-esophageal fistula. Our patient was a 32-year-old male with a history of poorly controlled diabetes. Over the months, he had complained of productive coughs and dyspnea, which had lately been joined by dysphagia. He also claimed to have lost considerable weight (10 kg) during the previous 3 months. Barium swallow showed an abnormal flow of contrast between the bronchus and esophagus, suggesting a broncho-esophageal fistula. Computed tomography of the thorax revealed a broncho-esophageal fistula between the left main bronchus (LMB) and esophagus. He had a bronchoscopy the next day, which revealed necrosis and a broncho-esophageal fistula in the LMB. A bronchial biopsy showed typical hyphae with necrotic tissue, indicating mucormycosis. The patient's antimycotic medication (liposomal amphotericin) was started and a prompt surgery consult was ordered. The patient, however, passed away from massive hemoptysis. We described a rare case of pulmonary mucormycosis with broncho-esophageal fistula in a patient with poorly controlled diabetes. The rarity of this combination highlights the associated diagnostic and treatment hurdles. Early detection, antifungal medication, as soon as possible surgical debridement of involved tissues, and a multidisciplinary approach could improve patient outcomes.
PubMed: 38947542
DOI: 10.1002/ccr3.9093 -
The alarmin IL-33 exacerbates pulmonary inflammation and immune dysfunction in SARS-CoV-2 infection.IScience Jun 2024Dysregulated host immune responses contribute to disease severity and worsened prognosis in COVID-19 infection and the underlying mechanisms are not fully understood. In...
Dysregulated host immune responses contribute to disease severity and worsened prognosis in COVID-19 infection and the underlying mechanisms are not fully understood. In this study, we observed that IL-33, a damage-associated molecular pattern molecule, is significantly increased in COVID-19 patients and in SARS-CoV-2-infected mice. Using IL-33 mice, we demonstrated that IL-33 deficiency resulted in significant decreases in bodyweight loss, tissue viral burdens, and lung pathology. These improved outcomes in IL-33 mice also correlated with a reduction in innate immune cell infiltrates, i.e., neutrophils, macrophages, natural killer cells, and activated T cells in inflamed lungs. Lung RNA-seq results revealed that IL-33 signaling enhances activation of inflammatory pathways, including interferon signaling, pathogen phagocytosis, macrophage activation, and cytokine/chemokine signals. Overall, these findings demonstrate that the alarmin IL-33 plays a pathogenic role in SARS-CoV-2 infection and provides new insights that will inform the development of effective therapeutic strategies for COVID-19.
PubMed: 38947521
DOI: 10.1016/j.isci.2024.110117 -
Infection and Drug Resistance 2024To analyze the effectiveness of the "Xinjiang Model" for tuberculosis prevention and control in Kashgar Prefecture, Xinjiang, and to explore the determinants of the...
OBJECTIVE
To analyze the effectiveness of the "Xinjiang Model" for tuberculosis prevention and control in Kashgar Prefecture, Xinjiang, and to explore the determinants of the policy implementation effect.
METHODS
The registration data of pulmonary tuberculosis (PTB) patients in Kashgar Prefecture from 2012 to 2021 were collected to describe the temporal trend of registered incidence. A questionnaire survey was conducted among PTB patients registered and treated in the tuberculosis management information system in Zepu and Shache Counties from January 2022 to July 2023 to collect and analyze "Xinjiang model" determinants of effectiveness.
RESULTS
The PTB registered incidence in Kashgar Prefecture showed a significant increasing trend from 2012 to 2018 (APC=18.7%) and a significant decreasing trend from 2018-2021 (APC=-28.8%). Among the Kashgar Prefecture, compared with average registered incidence in 2012-2017, registered incidence in 2021 in Shufu, Maigaiti, and Zepu Counties had a greater decline rate of 58.68%, 57.16%, and 54.02%, respectively, while the registered incidence in 2021 in Shache County increased by 6.32%. According to the comprehensive analysis of the factors affecting the effect of policy implementation, the proportion of PTB patients in Zepu County whose health status has now significantly improved compared with that before treatment was significantly greater than that in Shache County (<0.05); patients in Shache County were significantly less aware than those in Zepu County of how to take tuberculosis drugs, precautions, adverse reactions, and regular reviews during treatment; the factors that accounted for the greater proportion of heavy treatment burden in both Shache and Zepu Counties were discomfort caused by taking or injecting drugs, accounting for 12.8% and 8.7%, respectively.
CONCLUSION
The "Xinjiang model" can effectively control the epidemic situation of tuberculosis in Kashgar, and the knowledge of tuberculosis treatment, adverse reactions to tuberculosis drugs, and treatment costs were the determinants of the effectiveness of policy implementation.
PubMed: 38947373
DOI: 10.2147/IDR.S459228 -
Frontiers in Immunology 2024Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of...
INTRODUCTION
Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease.
METHODS
To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa.
RESULTS
Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1.
DISCUSSION
Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis.
PubMed: 38947330
DOI: 10.3389/fimmu.2024.1422836 -
Frontiers in Medicine 2024Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains...
BACKGROUND
Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses.
METHODS
Genetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy.
RESULTS
Genetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02-1.07, = 0.0001), with a Bonferroni-adjusted -value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03-1.13, = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02-1.06, = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis.
CONCLUSION
This MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.
PubMed: 38947239
DOI: 10.3389/fmed.2024.1408297 -
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 -
The Pan African Medical Journal 2024Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our...
Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4 month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
Topics: Humans; Male; Young Adult; Antitubercular Agents; Magnetic Resonance Imaging; Epididymis; Tuberculosis, Male Genital; Immunocompetence; Orchiectomy; Seizures; Anticonvulsants; Tuberculoma, Intracranial
PubMed: 38946746
DOI: 10.11604/pamj.2024.48.2.42965 -
International Journal of Language &... Jul 2024Based on stakeholder conversations, speech and language therapists have anecdotally observed cases of dysphagia with suspected laryngeal hypersensitivity. These... (Review)
Review
BACKGROUND
Based on stakeholder conversations, speech and language therapists have anecdotally observed cases of dysphagia with suspected laryngeal hypersensitivity. These presentations have been coined as 'muscle tension dysphagia' often with concurrent laryngeal sensitivity symptoms. However, the role of laryngeal hypersensitivity in dysphagia is not fully understood. Knowledge user engagement highlights a lack of clarity around diagnosis and investigative approaches, limited clinical guidance and inconsistent practice, which leads to inequity in service delivery and care.
AIM
To identify and present the published literature regarding the definitions and clinical identification tools used during the management of laryngeal hypersensitivity related dysphagia.
METHODS & PROCEDURES
A scoping review was conducted following Joanna Briggs Institute methodology and EQUATOR PRISMA-ScR guidance. Patient and stakeholder engagement was embedded at each review stage. The protocol was registered with the Open Science Framework: DOI 10.17605/OSF.IO/CUXYN. A multidatabase search strategy identified literature published between 2012 and 2022. A narrative description was used to report the study findings.
OUTCOMES & RESULTS
The search identified 2590 citations. The full paper screening was completed on 88 studies, with 17 studies included in data extraction. There was a wide range of terminology and assessment approaches which varied across different clinical settings. The most cited term was 'muscle tension dysphagia'. The most common assessments tools were videofluoroscopy, fibreoptic endoscopic evaluation of swallowing and videostroboscopy, predominantly used in speech and language therapy and/or Ear, Nose and Throat settings. Gastroesophageal and respiratory investigations were less frequently cited.
MAIN CONTRIBUTION
This review details the current evidence related to the terminology and assessment tools cited in laryngeal hypersensitivity related dysphagia to improve clinician knowledge and understanding. Patient and stakeholder involvement indicated that future research needs to: optimize consensus of terminology, and improve consistent identification methods, service provision and treatment approaches.
CONCLUSIONS & IMPLICATIONS
This review highlights the lack of consistent terminology across the literature. A wide range of assessment tools report nonspecific positive clinical features and a lack of significant instrumental assessment findings. Patients and stakeholders identify the research priorities should improve clinician awareness, knowledge, guidance and evidence to support patient care.
WHAT THIS PAPER ADDS
What is already known on the subject Swallowing difficulties can occur in adults for a number of different reasons, such as neurological, respiratory or physiological conditions. Swallowing difficulties with no evidence of biomechanical or structural impairment on instrumental assessment and of unknown cause (termed idiopathic functional dysphagia or medically unexplained dysphagia) is a poorly understood phenomenon. More recently, concurrent oropharyngeal dysphagia and laryngeal hypersensitivity and/or muscle tension have been posited as a potential underlying mechanism. What this study adds to the existing knowledge This scoping review contributes to our expanding knowledge of the role of laryngeal hypersensitivity in dysphagia by providing an overview of the current evidence related to the terminology and assessment tools reported in the literature. Embedded patient and stakeholder involvement further deepens real-world insights into the increased referrals for these individuals with increasing uncertainty in how to best assess, manage and support patients. Patients equally have reported that reduced professional awareness and inequalities in service delivery pathways result in poor patient experience and quality of life, and healthcare economic burden. What are the potential or actual clinical implications of this work? This scoping review draws our attention to an area of practice which has received little attention in both clinical practice and academic research. First, the study raises awareness of this population and the impact for services, speech and language therapists and clinicians; and second, highlights evidence-practice gaps with seldom consistency in the use of terminology and assessment approaches. The study provides priority research themes to expand our knowledge and understanding, as guided by the literature and patient and stakeholder input.
PubMed: 38946667
DOI: 10.1111/1460-6984.13085 -
Clinical Toxicology (Philadelphia, Pa.) Jul 2024Carbon monoxide poisoning is associated with severe damage to various organs. In this study, we aimed to determine if previous carbon monoxide poisoning was associated...
INTRODUCTION
Carbon monoxide poisoning is associated with severe damage to various organs. In this study, we aimed to determine if previous carbon monoxide poisoning was associated with an increased risk of lung diseases.
METHODS
The study population was derived from the National Health Insurance Service database of Korea between 1 January 2002 and 31 December 2021. Adults with carbon monoxide poisoning, with at least one visit to medical facilities between 2002 and 2021, were included. For comparison, an equal number of matched controls with the same index date were selected from the database.
RESULTS
A total of 28,618 patients with carbon monoxide poisoning and 28,618 matched controls were included in this study. Approximately 42.8 per cent of the patient and control groups were female, with a mean age of 51.3 years. In patients with carbon monoxide poisoning, there was a significant increase in the risk of lung cancer (adjusted hazard ratio, 1.84; 95 per cent confidence interval, 1.42-2.39; < 0.001), chronic obstructive pulmonary disease (adjusted hazard ratio, 1.60; 95 per cent confidence interval, 1.36-1.89; < 0.001), pulmonary tuberculosis (adjusted hazard ratio, 1.46; 95 per cent confidence interval, 1.13-1.88; = 0.003), and non-tuberculous mycobacterial infection (adjusted hazard ratio, 1.54; 95 per cent confidence interval, 1.01-2.36; = 0.047).
DISCUSSION
In this retrospective cohort study, previous carbon monoxide poisoning was associated with an increased risk of lung cancer, chronic obstructive pulmonary disease, pulmonary tuberculosis, and non-tuberculous mycobacterial infection. Further studies are needed to confirm such an association in other populations and the risk of lung diseases due to the toxic effect of carbon monoxide from different sources.
CONCLUSIONS
Previous carbon monoxide poisoning was associated with an increased risk of lung diseases, but the relative importance of the causes and sources of exposure was not known. The long-term management of survivors of acute carbon monoxide poisoning should include monitoring for lung cancer, chronic obstructive pulmonary disease, pulmonary tuberculosis, and non-tuberculous mycobacterial infection.
PubMed: 38946481
DOI: 10.1080/15563650.2024.2371020