Case report: Diagnosis of Talaromyces marneffei infection in an HIV-negative patient with septic shock and high-titer anti-interferon gamma autoantibodies by metagenomic next-generation sequencing.

Background: Sepsis is a life-threatening condition caused by a dysfunctional response to infection from the host. Septic shock, a subset of sepsis, caused by Talaromyces marneffei infection (talaromycosis) has rarely been reported. Owing to its slow culture and low yield, talaromycosis is typically misdiagnosed in HIV-negative patients as other infections, such as tuberculosis, bacterial pneumonia, and lung cancer, especially in non-endemic regions. Early and accurate diagnosis as well as efficient treatment options are required to improve prognosis. Method: A 30-year-old HIV-negative Chinese woman from a non-endemic area of T. marneffei was initially misdiagnosed with tuberculosis. She had a poor response to anti-tuberculosis treatment. On July 16, 2022, she was admitted to our hospital; the patient developed septic shock on the third day after hospitalization and was ultimately diagnosed with talaromycosis via metagenomic next-generation sequencing (mNGS). Result: The condition of the patient improved after appropriate treatment with amphotericin B. Furthermore, enzyme-linked immunosorbent assay results confirmed that the patient had a high-titer of anti-interferon gamma (IFN-γ) autoantibodies. Conclusion: HIV-negative individuals with anti-IFN-γ autoantibodies typically have relapsing, refractory, and fatal infections, such as talaromycosis, which is typically misdiagnosed in the initial course of the disease. This can lead to septic shock. Clinicians should be aware that they may encounter HIV-negative patients with T. marneffei infection in non-endemic areas. Thus, mNGS is an effective technology for detecting T. marneffei infection. Additionally, the detection of anti-IFN-γ autoantibodies in these patients would aid in knowing their susceptibility to fatal infections.

Metagenomic next-generation sequencing confirms the diagnosis of Legionella pneumonia with rhabdomyolysis and acute kidney injury in a limited resource area: a case report and review.

Background: Legionella pneumonia, rhabdomyolysis, and acute kidney injury are called the Legionella triad, which is rare and associated with a poor outcome and even death. Early diagnosis and timely treatment are essential for these patients. Case presentation: A 63-year-old man with cough, fever, and fatigue was initially misdiagnosed with common bacterial infection and given beta-lactam monotherapy but failed to respond to it. Conventional methods, including the first Legionella antibody test, sputum smear, and culture of sputum, blood, and bronchoalveolar lavage fluid (BALF) were negative. He was ultimately diagnosed with a severe infection of Legionella pneumophila by metagenomics next-generation sequencing (mNGS). This patient, who had multisystem involvement and manifested with the rare triad of Legionella pneumonia, rhabdomyolysis, and acute kidney injury, finally improved after combined treatment with moxifloxacin, continuous renal replacement therapy, and liver protection therapy. Conclusion: Our results showed the necessity of early diagnosis of pathogens in severe patients, especially in Legionnaires' disease, who manifested with the triad of Legionella pneumonia, rhabdomyolysis, and acute kidney injury. mNGS may be a useful tool for Legionnaires' disease in limited resource areas where urine antigen tests are not available.

Delineating asthma according to inflammation phenotypes with a focus on paucigranulocytic asthma.

ABSTRACT: Asthma is characterized by chronic airway inflammation and airway hyper-responsiveness. However, the differences in pathophysiology and phenotypic symptomology make a diagnosis of "asthma" too broad hindering individualized treatment. Four asthmatic inflammatory phenotypes have been identified based on inflammatory cell profiles in sputum: eosinophilic, neutrophilic, paucigranulocytic, and mixed-granulocytic. Paucigranulocytic asthma may be one of the most common phenotypes in stable asthmatic patients, yet it remains much less studied than the other inflammatory phenotypes. Understanding of paucigranulocytic asthma in terms of phenotypic discrimination, distribution, stability, surrogate biomarkers, underlying pathophysiology, clinical characteristics, and current therapies is fragmented, which impedes clinical management of patients. This review brings together existing knowledge and ongoing research about asthma phenotypes, with a focus on paucigranulocytic asthma, in order to present a comprehensive picture that may clarify specific inflammatory phenotypes and thus improve clinical diagnoses and disease management.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury.

There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Anticoagulation therapy for pulmonary embolism involving a myxoma mimicking, giant type C thrombus: A case report.

Right heart thrombus (RHTh) with concurrent acute pulmonary embolism (PE) is rare and can seriously destabilize hemodynamics, leading to an emergency situation with high mortality. Diagnosis and treatment of RHTh with acute PE are not yet standardized. There are few reports of acute PE concurrent with RHTh and even less is known about patients with a right heart mural thrombus. For physicians, the diagnostic choice and treatment of these patients are particularly difficult due to the lack of knowledge. Here, we report a rare case of partial mural RHTh (type C RHTh) with acute PE. The mural mass in the right heart was initially diagnosed as atrial myxoma according to transthoracic echocardiography (TTE), and both pulmonary embolus and the mural mass were completely absorbed after administering Rivaroxiban. This case suggests that TTE alone is insufficient to identify and diagnoses a right heart mural mass such as this. However, novel oral anticoagulants may be effective at alleviating PE with type C RHTh.

Prognostic Performance of Hestia Criteria in Acute Pulmonary Embolism: A Systematic Review and Meta-Analysis.

Previous studies have suggested that Hestia criteria could effectively identifying patients with acute pulmonary embolism (PE) who were at low risk of mortality for outpatient treatment or early discharge. But the performance of Hestia criteria in stratifying patients at different risk class is still unknown. We sought to comprehensively evaluate the prognostic impact of Hestia criteria for PE. The literatures search was conducted in PubMed, Web of Science and EMBASE from 1 August 2011 to 31 October 2021. Finally, Eight studies with 4110 patients were included in our meta-analysis. Overall, the pool percentage of patients classified as low-risk group and high-risk group were 41.4%% and 58.6% respectively, and the all-course mortality rates of each group were 2.3% and 10.6%, respectively. The pooled rate of PE-related composite adverse outcomes in high-risk group was increasingly higher than in low-risk group (15.7% vs 4.4%). High risk group was also markedly associated with overall mortality (OR: 7.21, 95%CI: 4.96-10.46, p < 0.00001), and PE-related adverse outcomes (OR:5.38, 95% CI:3.95-7.32, p < 0.00001). The pooled sensitivity, specificity, PLR, NLR of Hestia criteria for overall mortality were 0.90 (95% CI:0.83-0.94), 0.43 (95% CI:0.31-0.55), 1.6 (95% CI:1.3-1.9), 0.23 (95% CI: 0.15-0.35), respectively. The area under SROC curve (AUC) was 0.81 (95% CI: 0.77-0.84). The result of our meta-analysis indicate that Hestia criteria can effectively identify PE patients at low risk of poor prognosis with high sensitivity and NPV, but its prognostic role in patients with higher risk class still need to be verified.

Genomic Analysis Reveals the Prognostic and Immunotherapeutic Response Characteristics of Ferroptosis in Lung Squamous Cell Carcinoma.

INTRODUCTION: Recent studies have reported that ferroptosis is an iron-dependent cell death process and is a potential therapeutic target in various tumours. The purpose of this study was to establish a new algorithm based on the ferroptosis score to ascertain the prognosis and response to immunotherapy of patients with lung squamous cell carcinoma (LUSC). METHODS: The RNA-seq data of patients with LUSC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases and merged after removing the inter batch differences. Based on the expression of the ferroptosis-related genes, unsupervised consistent cluster analysis was performed to obtain various ferroptosis-related subgroups. These subgroups were analysed to obtain differentially expressed genes (DEGs). Subsequently, multiple gene clusters were obtained by unsupervised consistent cluster analysis based on the expression of the DEGs. The Boruta algorithm was used to calculate the ferroptosis score. RESULTS: There were significant differences in prognosis amongst the various ferroptosis-related and gene clusters. In addition, the gene set variation analysis revealed that the different ferroptosis-related clusters and gene clusters demonstrated differences in biological pathways. The ferroptosis scores positively correlated with the tumour mutation burden, and patients with lower scores had a better prognosis. In addition, the ferroptosis score was accurate in predicting the effectiveness of immunotherapy. CONCLUSION: There were significant differences in the prognosis and immunotherapy response of patients with LUSC with different ferroptosis scores. Therefore, a comprehensive clinical evaluation of the ferroptosis score of each patient with LUSC is clinically significant.

Prognostic role of elevated lactate in acute pulmonary embolism: A systematic review and meta-analysis.

BACKGROUND: Previous studies have shown elevated lactate was a good predictor for the prognosis of pulmonary embolism (PE). However, due to low number of patients and different expression of blood lactate in separate study, these results are inconsistent. Therefore, the aim of this meta-analysis is to evaluate the relationship between increased lactate levels and adverse outcome in acute PE. METHOD: The literatures search was conducted in PubMed, Web of Science, and EMBASE until May 29, 2021. RESULTS: Finally, 6 studies with 1706 patients were included in our meta-analysis. High lactate levels were markedly associated with overall mortality both in unselected PE patients (OR 5.13, 95% CI: 3.36-7.86, p < .00,001) and normotensive PE patients (OR 4.54, 95% CI: 2.64-7.80, p < .00,001), and PE-related short-term mortality in patients with elevated lactate was significantly higher than that in patients with normal levels (OR 9.05, 95% CI :4.08-20.10, p < .00,001). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of lactate for predicting overall mortality in patients with acute PE were 0.67 (95% CI: 0.43-0.85), 0.73 (95% CI: 0.60-0.83), 2.5 (95% CI: 2.0-3.1), and 0.45 (95% CI: 0.26-0.78), respectively. The area under SROC curve (AUC) was 0.76 (95% CI: 0.73-0.80). CONCLUSION: The result of our meta-analysis indicate that elevated blood lactate is a good predictor for overall mortality and short-term mortality in patients with acute PE, and can be routinely measured in risk stratification, but its prognostic role in patients with different risk classes still need to be verified.

Pyogenic thigh abscess caused by Streptococcus constellatus subsp. constellatus in a patient with exacerbation of bronchiectasis: a case report.

Streptococcus constellatus (S. constellatus) is a Gram-positive commensal bacterium that is commonly found in the oral, nasal, pharyngeal, gastrointestinal, and urogenital tracts. It can be further consisted by three subspecies: subsp, constellatus, subsp. pharynges, and subsp. viborgensis. As an opportunistic pathogen, S. constellatus can cause abscesses and bacteremia, so infection requires timely and accurate identification in clinical practice. There are a few case reports describing the range of infections caused by S. constellatus, which include intracardiac, thoracic, intracranial, and abdominal infections. Here we report the first case of thigh abscess caused by S. constellatus subsp. constellatus which was rarely insensitive to penicillin in a patient with exacerbation of bronchiectasis. The patient improved significantly after receiving antibiotic therapy with ceftriaxone and vancomycin, as well as percutaneous catheter drainage guided by color ultrasonography. The thigh abscess did not recur during follow-up. This case report demonstrates that although S. constellatus is a rare infectious pathogen, it is important to gain a better understanding of the range of possible infections to ensure timely diagnosis. Furthermore, although the prognosis of most patients with such infections is relatively good, the timely identify the resistant strains and administration of sensitive antibiotics along with abscess drainage may ensure effective treatment.

Artificial Intelligence and Machine Learning in Chronic Airway Diseases: Focus on Asthma and Chronic Obstructive Pulmonary Disease.

Chronic airway diseases are characterized by airway inflammation, obstruction, and remodeling and show high prevalence, especially in developing countries. Among them, asthma and chronic obstructive pulmonary disease (COPD) show the highest morbidity and socioeconomic burden worldwide. Although there are extensive guidelines for the prevention, early diagnosis, and rational treatment of these lifelong diseases, their value in precision medicine is very limited. Artificial intelligence (AI) and machine learning (ML) techniques have emerged as effective methods for mining and integrating large-scale, heterogeneous medical data for clinical practice, and several AI and ML methods have recently been applied to asthma and COPD. However, very few methods have significantly contributed to clinical practice. Here, we review four aspects of AI and ML implementation in asthma and COPD to summarize existing knowledge and indicate future steps required for the safe and effective application of AI and ML tools by clinicians.

Specific regulator of eosinophil apoptosis: Siglec-8-new hope for bronchial asthma treatment.

OBJECTIVE: It is known that Siglec-8 is selectively expressed on human eosinophils at a high level and mediates eosinophil apoptosis when crosslinked with its antibody. The aim of our review is to elucidate the molecular and biological characteristic of Siglec-8 and then discuss the function and possible mechanisms of Siglec-8 in eosinophils. Thereby, we will expand our understanding to the regulation of eosinophil apoptosis, and provide important clues to the treatment of asthma and other hyper-eosinophilic diseases. DATA SOURCES: Most articles were identified by searching of PubMed online resources using the key term Siglecs. STUDY SELECTION: Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected. RESULTS: Siglec-8 is selectively expressed on human eosinophil and can specifically induce eosinophil apoptosis. CONCLUSION: The restricted expression of Siglec-8 on human eosinophil and the rapid progress in understanding its role as cell signaling and activation of death receptors have made it an attractive target for treatment of asthma and other hyper-eosinophilic diseases.

Expression and preliminary functional analysis of Siglec-F on mouse macrophages.

Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a mouse functional paralog of human Siglec-8 that induces apoptosis in human eosinophils, and therefore may be useful as the basis of treatments for a variety of disorders associated with eosinophil hyperactivity, such as asthma. The expression pattern and functions of this protein in various cell types remain to be elucidated. The aim of this study was to determine the expression of Siglec-F on mouse macrophages by immunocytochemical staining, and also to investigate the effects of Siglec-F engagement by a Siglec-F antibody on phagocytic activity of macrophages. The results showed that Siglec-F expression was detected on mouse alveolar macrophages, but not on peritoneal macrophages. Furthermore, Siglec-F engagement did not affect the phagocytic activity of alveolar macrophages in the resting state or in the activated state following stimulation by the proinflammatory mediator tumor necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS). Siglec-F expression on alveolar macrophages may be a result of adaptation. Macrophages actively regulate immune responses via production of cytokines. Therefore, further investigation of the effects of Siglec-F engagement on immune mediators or cytokines released by alveolar macrophages is required.