A patient with AL amyloidosis presenting with refractory tuberculosis, chest tightness and hypotension: case report.

INTRODUCTION: Immunoglobulin light chain (AL) amyloidosis presents a clinical spectrum characterized by diverse manifestations and involvement of multiple organs, posing a significant diagnostic challenge for physicians. METHODS AND RESULTS: We present a case of a patient admitted to our hospital due to recurrent cough and sputum, which was initially diagnosed as refractory tuberculosis. Throughout his hospitalization, the patient experienced distressing symptoms, including uncontrollable chest tightness, hypotension, and fever. Noteworthy observations included a persistent elevation in cardiac biomarkers, indicative of cardiac damage. Bronchoalveolar lavage revealed the presence of various pathogenic microorganisms, while bone marrow flow cytometry demonstrated the existence of clonal plasma cells. Additionally, the urine free light chain assay detected the presence of M protein, and the positive congo red staining of the abdominal wall fat biopsy confirmed amyloid deposition in the tissues. Taking into account the patient's clinical presentation and the examination findings, we reached a conclusive diagnosis of immunoglobulin light chain (AL) amyloidosis. CONCLUSION: This case serves as a reminder for physicians to consider rare diseases like AL amyloidosis when patients present with symptoms involving multiple organ systems such as heart, lung and kidney that are unresponsive to conventional treatment options.

Diagnostic and Therapeutic Challenges in Lemierre Syndrome: A Case Report Using Metagenomic Next Generation Sequencing.

Lemierre syndrome (LS) is a rare and life-threatening condition predominantly caused by Fusobacterium necrophorum. Currently, there are no standardized clinical guidelines for LS management. Here, we describe the case of a 40-year-old male with fever, productive cough, and dyspnea but no sore throat. Diagnostic radiological examinations revealed multiple pulmonary cavitary nodules and an internal jugular vein occlusion. Metagenomic Next-Generation Sequencing (mNGS) of the alveolar lavage fluid identified Fusobacterium necrophorum, thereby confirming the diagnosis of LS. Intriguingly, the patient exhibited a delayed clinical response despite receiving the appropriate antibiotic. After integrating tigecycline into the treatment to address potential co-infecting bacteria, we observed a marked improvement in his clinical symptoms. Subsequent follow-up over 12 weeks post-discharge revealed complete alleviation of symptoms, and a chest CT scan showed marked regression of the lung lesions.

The value of performance status in predicting venous thromboembolism in lung cancer patients treated with immune checkpoint inhibitors.

INTRODUCTION: The incidence of venous thromboembolism (VTE) is notably high in lung cancer patients, particularly among those treated with immune checkpoint inhibitors (ICIs). Previous studies have focused on the relationship between Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) and VTE risk in immune checkpoint inhibitor therapy, but available evidence is inconsistent. METHODS: The clinical data of lung cancer patients treated with ICIs were collected and analyzed from West China Hospital between January 2018 and March 2022. ECOG PS score was measured on admission. The primary outcome was the incidence of VTE, encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE). Multivariate logistic regression analysis was conducted to calculate the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: A total of 1115 lung cancer patients receiving ICIs were eligible for this study, VTE developed in 105 (9.4%) during the 12-month follow-up, of which 95 (8.5%) had DVT,14 (1.3%) had definite PE. Poor ECOG PS (PS ≥ 2) was associated with an increased risk for VTE (OR = 5.405, 95% CI = 3.067-9.525, P < 0.001), DVT (OR = 4.669, 95% CI = 2.588-8.427, P < 0.001) and PE (OR = 8.413, 95% CI = 2.565-27.600, P < 0.001) after multivariable adjustment in the study cohort. CONCLUSION: VTE occurred in 9.4% of lung cancer patients treated with ICIs, and poor performance status was associated with an increased risk of VTE.

The role of type VI secretion system genes in antibiotic resistance and virulence in Acinetobacter baumannii clinical isolates.

Introduction: The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed. Methods: The importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated. Results: A higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella. Discussion: The above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.

A gut microbiota-bile acid axis promotes intestinal homeostasis upon aspirin-mediated damage.

Aspirin-related gastrointestinal damage is of growing concern. Aspirin use modulates the gut microbiota and associated metabolites, such as bile acids (BAs), but how this impacts intestinal homeostasis remains unclear. Herein, using clinical cohorts and aspirin-treated mice, we identified an intestinal microbe, Parabacteroides goldsteinii, whose growth is suppressed by aspirin. Mice supplemented with P. goldsteinii or its BA metabolite, 7-keto-lithocholic acid (7-keto-LCA), showed reduced aspirin-mediated damage of the intestinal niche and gut barrier, effects that were lost with a P. goldsteinii hdhA mutant unable to generate 7-keto-LCA. Specifically, 7-keto-LCA promotes repair of the intestinal epithelium by suppressing signaling by the intestinal BA receptor, farnesoid X receptor (FXR). 7-Keto-LCA was confirmed to be an FXR antagonist that facilitates Wnt signaling and thus self-renewal of intestinal stem cells. These results reveal the impact of oral aspirin on the gut microbiota and intestinal BA metabolism that in turn modulates gastrointestinal homeostasis.

Prognostic value of pretreatment serum fibrinogen in young patients with small cell lung cancer: A cross-sectional study.

Objective: To explored the prognostic value of pretreatment serum fibrinogen level in young patients with small cell lung cancer (SCLC). Methods: The concentrations of serum fibrinogen of 183 young (<50 years old) SCLC patients were measured. The association of baseline serum fibrinogen level and clinical outcome was analyzed by survival analysis. Results: Hyperfibrinogenemia was significantly associated with American Veterans Administration Lung Study Group stage and surgery treatment. The survival analysis indicated that patients with hypefibrinogenemia had worse outcome than patients with normal fibrinogen. Pretreatment serum fibrinogen level was identified as a worse independent survival predictor in young SCLC. The hazard ratio was 1.420 (95% confidence interval: 1.035-1.947). Conclusions: Pretreatment serum fibrinogen is independent associated with overall survival in patients with young SCLC.

Common nutritional/inflammatory indicators are not effective tools in predicting the overall survival of patients with small cell lung cancer undergoing first-line chemotherapy.

Objective: Various studies have investigated the predictive significance of numerous peripheral blood biomarkers in patients with small cell lung cancer (SCLC). However, their predictive values have not been validated. This study assessed and evaluated the ability of common nutritional or inflammatory indicators to predict overall survival (OS) in patients with SCLC who received first-line chemotherapy. Methods: Between January 2008 and July 2019, 560 patients with SCLC were enrolled at the Sichuan University West China Hospital. Eleven nutritional or inflammatory indices obtained before chemotherapy were evaluated. The cutoff values of continuous peripheral blood indices were confirmed through maximally selected rank statistics. The relationship of peripheral blood indices with OS was investigated through univariate and multivariate Cox regression analyses. Harrell's concordance (C-index) and time-dependent receiver operating characteristic curve were used to evaluate the performance of these indices. Results: A total of 560 patients with SCLC were enrolled in the study. All the patients received first-line chemotherapy. In the univariate Cox analysis, all indices, except the Naples score, were related to OS. In the multivariate analysis, albumin-globulin ratio was an independent factor linked with prognosis. All indices exhibited poor performance in OS prediction, with the area under the curve ranging from 0.500 to 0.700. The lactic dehydrogenase (LDH) and prognostic nutritional index (PNI) were comparatively superior predictors with C-index of 0.568 and 0.550, respectively. The LDH showed incremental predictive values, whereas the PNI showed diminishing values as survival time prolonged, especially for men or smokers. The LDH with highest sensitivity (0.646) and advanced lung cancer inflammation index (ALI) with highest specificity (0.952) were conducive to identifying death and survival at different time points. Conclusion: Common inflammatory or nutritional biomarkers are only marginally useful in predicting outcomes in patients with SCLC receiving first-line chemotherapy. Among them, LDH, PNI, and ALI are relatively promising biomarkers for prognosis evaluation.

Case report: Identification of acute promyelocytic leukemia during osimertinib resistance followed by granulocyte colony-stimulating factor and pembrolizumab.

Background: The occurrence of acute promyelocytic leukemia (APL) during the management of lung cancer is rare and life-threatening. It was mainly reported to be secondary to chemoradiotherapy. A few studies reported an increased incidence of therapy-related acute promyelocytic leukemia (t-APL) after gefitinib became available. Case presentation: We reported a patient who developed thrombocytopenia after receiving oral osimertinib in combination with intensity-modulated radiotherapy (IMRT). For half a year, she had an unrecoverable low platelet count, which progressed to concomitant leukopenia and the transient appearance of orthochromatic normoblasts in the peripheral blood test, indicating a dormant myeloid disorder. Due to simultaneous resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), pembrolizumab and granulocyte colony-stimulating factor (G-CSF) were administered, revealing prominent signs of hematological malignancy in a peripheral blood test that was later identified as t-APL. Conclusion: In general, patients undergoing EGFR-TKI combined with local radiotherapy should be concerned about their hematological assessment. If patients exhibit unrecoverable abnormalities in routine blood tests, a secondary nonsolid malignancy other than myelosuppression should be considered, and further lung cancer treatment should be discontinued.