Case report: Acquired resistance to crizotinib from a MET Y1230H mutation in a patient with non-small cell lung cancer and KIF5B-MET fusion.

Background: The c-met proto-oncogene (MET) serves as a significant primary oncogenic driver in non-small cell lung cancer (NSCLC) and has the potential to fuse with other genes, such as KIF5B, although it occurs infrequently. Only a limited number of reported cases have examined the clinical efficacy of crizotinib in patients with KIF5B-MET gene fusion, with no known data regarding acquired resistance to crizotinib and its potential mechanisms. In this report, we present the clinical progression of a female patient diagnosed with NSCLC and harboring a KIF5B-MET gene fusion. Case description: The patient initially exhibited partial response to first-line crizotinib treatment, albeit for a short duration and with limited efficacy. Subsequent disease progression revealed the emergence of a secondary MET mutation, specifically MET Y1230H, leading to acquired resistance to crizotinib. Conclusion: The reporting of this case is imperative for informing clinical practice, given the uncommon occurrence of NSCLC with MET fusion, displaying responsiveness to MET tyrosine kinase inhibitor therapy, as well as the emergence of the secondary Y1230H alteration as a potential resistance mechanism.

Blood urea nitrogen-to-albumin ratio independently predicts 30-day mortality in acute respiratory failure patients: a retrospective cohort study.

Background: It is crucial to identify patients at high risk for acute respiratory failure (ARF) to provide appropriate and optimal clinical treatment. While previous studies have explored the use of prognostic biomarkers based on a combination of blood urea nitrogen (BUN) and albumin levels, no reports to date have evaluated its utility across a wide range of ARF etiologies in a large and diverse critical care population. Therefore, we aimed to ascertain the association between the BUN-to-albumin ratio (BAR) and mortality in these patients. Methods: Data recorded in the first 24 h following intensive care unit (ICU) admission, including demographics, vital signs, laboratory test results, comorbidities, and score systems were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A general additive model was used to determine whether there was a non-linear relationship between BAR and 30-day mortality. A multivariate Cox analysis was performed to measure the association between them. Results: The study enrolled 9,734 patients with ARF. In comparison to survivors, non-survivors exhibited higher BAR [10.79 (6.25-18.81) vs. 7.35 (4.48-13.62), P<0.001]. The correlation between baseline BAR and 30-day all-cause mortality in patients with ARF was non-linear, with a significant inflection point (11.76 mg/g). The Kaplan-Meier curve demonstrated that ARF patients had higher 30-day all-cause mortality rates when they had higher BAR levels (>11.76 mg/g) with hazard ratio (HR) 1.54 [95% confidence interval (CI): 1.39-1.70]. Conclusions: A high BAR was linked to a higher risk of mortality in ARF patients. BAR is a straightforward and possibly useful prognostic biomarker for ARF.

Successful treatment with tislelizumab plus chemotherapy for SMARCA4-deficient undifferentiated tumor: a case report.

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT.

Sixteen cases of severe pneumonia caused by Chlamydia psittaci in South China investigated via metagenomic next-generation sequencing.

Introduction. Chlamydia psittaci is an important cause of community-acquired pneumonia (CAP). The spectrum of CAP due to Chlamydia psittaci ranges from mild, self-limited to acute respiratory failure and the early identification of this disease can be challenging. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid has the potential to improve the pathogen identification in severe CAP.Hypothesis/Gap Statement. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid has the potential to rapidly identify pathogens in severe CAP. The early identification and appropriate use of antibiotics can improve the prognosis of severe CAP caused by Chlamydia psittaci.Aim. The aim of the study is to describe the clinical spectrum of severe psittacosis pneumonia to provide a better understanding of this disease and to demonstrate that mNGS is an effective method for pathogen detection.Methodology. Retrospective case analysis from November 2019 to November 2020 was performed. Sixteen cases of severe psittacosis pneumonia were diagnosed through mNGS. Clinical features, laboratory findings, imaging features, treatment and outcome were summarized.Results. Frequent symptoms included fever (16/16, 100%), dyspnoea (16/16, 100%), cough (12/16, 75%), sputum (11/16, 69%) and headache (9/16, 56%). The median leukocytosis was within the normal range, while C-reactive proteins, CK, LDH, AST, D-Dimer were significantly elevated. The feature of computed tomography included ground-glass opacity with consolidation and multiple lobar distributions. The total number of sequences of Chlamydia psittaci identified from bronchoalveolar lavage by mNGS varied from 58 to 57115. Five patients underwent noninvasive mechanical ventilation, four patients underwent high flow humidified oxygen therapy and one patient underwent invasive mechanical ventilation. Two patients had septic shock needing vasoactive medications. All of the sixteen patients experienced full recoveries.Conclusion. The symptoms of severe CAP caused by Chlamydia psittaci were not typical while laboratory results may have some clues. The mNGS technology can early detect of psittacosis, reduce unnecessary use of antibiotics and short the course of the disease.