Linezolid effectively treats rifampicin-resistant tuberculosis (RR-TB) but can cause significant hematological toxicities linked to mitochondrial dysfunction in hematopoietic stem cells. Growth differentiation factor-15 (GDF-15) has been identified as a potential biomarker of this dysfunction. This study aimed to determine whether baseline GDF-15 levels can predict myelosuppression in RR-TB patients treated with linezolid. The study included patients with RR-TB from three referral hospitals who were treated with a linezolid-containing regimen for at least 4 weeks. Hematological parameters and GDF-15 levels were measured at baseline as well as at the 2nd and 4th-8th weeks of treatment. Ninety-seven subjects were included in this study. By the 2nd week of linezolid treatment, GDF-15 levels significantly increased from a baseline of 635.58 (407.31-1583.65) to 708.96 (378.09-2408.89)pg/ml (p = 0.003). By weeks 4-8, 65% of patients developed myelosuppression. A correlation was found between baseline GDF-15 levels and hemoglobin reduction at weeks 4-8 (r = 0.4, p < 0.001). Baseline GDF-15 levels > 950 pg/mL identified patients with more than a 25% reduction in hemoglobin (AUC 0.756, 95% CI 0.659-0.838). Baseline GDF-15 levels were correlated with hemoglobin changes during the 4th-8th weeks of linezolid treatment. These levels can predict myelosuppression, particularly hemoglobin changes, in patients with RR-TB undergoing long-term linezolid therapy.

Noninvasive ventilation (NIV) is the treatment of choice in cases of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, depressed mental status, frequently caused by AECOPD, represents a relative contraindication to NIV. This study evaluates the efficacy of NIV in patients with AECOPD with moderate to severe impairment of consciousness. In this monocentric, retrospective study, we included patients admitted to the emergency department (ED) from January 2018 to December 2022 for AECOPD, altered mental status (GCS ≤ 13 and/or KMS ≥ 2) and treated with NIV. Out of 919 patients admitted with acute respiratory failure, 228 (24.8%) met the inclusion criteria for AECOPD. Of these, 205 (90%) underwent NIV during the ED admissions without adverse events. In 48 patients (21.1%), NIV was withdrawn due to clinical improvement. Only 23 (10.1%) experienced NIV failure with worsening of hypoxemia and occurrence of hypotension, of whom 16 (7% of the total population) died in the ED. Severe neurological impairment (low GCS) was an independent predictor of mortality. Systolic and diastolic blood pressure, SpO2, pH value and lactate levels were predictive of early mortality. COVID-19 status did not significantly affect mortality rates. NIV was feasible and associated with successful outcomes in a majority of patients with AECOPD and moderate to severe neurological impairment. Specific parameters, including initial GCS, blood pressure, SpO2, and blood gas profiles, can help predict outcomes and treatment efficacy.

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ABSTRACTBackgroundIdiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease characterized by pathological pulmonary vascular remodeling and right heart failure. Current biomarkers for IPAH demonstrate limited clinical utility, necessitating the discovery of noninvasive serum biomarkers to facilitate early diagnosis and prognosis.ObjectiveTo identify novel serum biomarkers for IPAH using tandem mass tag–based quantitative proteomics and validate their clinical relevance.MethodsSerum samples from five IPAH patients and five age/sex‐matched healthy controls (discovery cohort) were analyzed by tandem mass tag proteomics to screen differentially expressed proteins (DEPs). Functional enrichment and protein–protein interaction network analyses were performed. Serum galectin‐3 binding protein (LGALS3BP) levels were validated by enzyme‐linked immunosorbent assay (ELISA) in an expanded cohort (30 IPAH patients vs. 30 controls).ResultsProteomic analysis identified 401 proteins and 1554 peptide fragments, with 114 DEPs between groups (47 up‐regulated and 67 down‐regulated). In biological processes, DEPs are primarily enriched in adaptive immune response, followed by signal transduction. Extracellular exosome and extracellular region are the most commonly enriched cell components. For molecular function, DEPs are mainly involved in antigen binding and calcium ion binding, with the top 30 Gene Ontology terms exhibiting similar distribution patterns between up‐ and down‐regulated DEPs. Pathway analysis revealed significant enrichment in complement/coagulation cascades, immune response, and extracellular matrix remodeling. LGALS3BP was observed to be significantly up‐regulated in IPAH serum compared with controls (fold change = 1.36, p < 0.001), a finding validated by independent ELISA (IPAH: 6.43 ± 1.73 μg/mL vs. controls: 2.33 ± 1.06 μg/mL; p < 0.001).ConclusionsIntegrated proteomic profiling and clinical validation provide the first evidence of elevated serum LGALS3BP in IPAH, indicating its putative role in pathogenesis and translational medicine.

ABSTRACTIntroductionThis retrospective cross‐sectional study examined the correlation between Systemic Immune‐Inflammation Index (SII) and in‐hospital mortality in patients with sepsis combined with chronic obstructive pulmonary disease (COPD) and explored the modifying effect of mechanical ventilation on this relationship.MethodsLogistic regression models were employed to explore the correlation between log SII and in‐hospital mortality. The receiver operating characteristic curve and decision curve analysis were used to examine the predictive value of log SII for in‐hospital mortality. Generalized linear regression analysis, logistic regression analysis, and restricted cubic spline were used to explore the associations among log SII, in‐hospital mortality, and mechanical ventilation states.ResultsA total of 1058 patients were enrolled. Log SII was an independent risk factor for in‐hospital mortality in patients with sepsis combined with COPD (odds ratios for Model 1, Model 2, Model 3, and Model 4 were 3.116, 2.847, 2.244, and 3.495, respectively; p < 0.005; log SII as an optimal‐threshold categorical variable). Additionally, mechanical ventilation was closely related to log SII (p < 0.05). There was a stronger correlation between log SII and in‐hospital mortality of patients who received mechanical ventilation, especially those with invasive mechanical ventilation (p < 0.05).ConclusionAn elevated SII independently predicts elevated in‐hospital mortality risk in sepsis–COPD patients. This association is strongly intensified by mechanical ventilation, particularly the invasive mode. SII serves as a valuable biomarker for risk stratification in this vulnerable population.

ABSTRACTBackgroundCOVID‐19 infection has been a major pandemic of this century, causing deaths, economic hardship, and poverty worldwide. At the moment, vaccination remains the most effective measure against this health challenge. This retrospective study assessed the efficacy of COVID‐19 vaccination in the affected patients who had been shown positive previously by polymerase chain reaction (PCR) tests.MethodsWe compared the retrospective records of 547 patients with COVID‐19 over the prior 18 months (Mar. 2021 to Sept. 2022). Data from the patients' hospital records were divided into two groups of vaccinated (N = 334) versus non‐vaccinated (N = 213) from individuals who had a prior positive PCR test. Subsequently, the patients' chest computed tomography (CT) images were evaluated and scored for the lung involvements based on a pathologically established scoring system.ResultsBased on the CT image scores, it was evident that the vaccination significantly reduced the lung involvements in these patients. The severity of lung involvements was significantly less in the vaccinated than in the non‐vaccinated group, regardless of being younger or older than 65 years old. Also, the arterial oxygen saturation was significantly greater in the vaccinated than in the non‐vaccinated patients. Lastly, the vaccination had a significant effect on lowering the mortality rate and intubation in patients older than 65 years. However, there was no significant difference between the vaccinated versus the non‐vaccinated groups with respect to their admission into the ICU at the local hospital.ConclusionsBased on the results, COVID‐19 vaccination reduced the severity of lung involvements in patients significantly. Hence, it can be considered a protective measure in reducing the disease burden.

To investigate the early effect of esketamine on the tumor metastatic microenvironment in patients with lung cancer. Sixteen adults aged 45-80 years with the American Society of Anesthesiologists (ASA) 1 to 3 were randomly divided into the experimental group (group E) and the control group (group C). Group E received esketamine at 1 mg/kg during anesthesia induction and a continuous infusion of 0.5 mg/kg/h during the surgery. Group C was given the same amount of normal saline infusion. Patient-controlled intravenous analgesia (PCIA) in group E was administered using dexmedetomidine (0.5 mg/kg) + esketamine (50 mg) + dexamethasone (5 mg). PCIA in group C was the same dose of dexmedetomidine and dexamethasone. Data were recorded at 14 points from admission to the third day after surgery (T0-14). Parameters recorded included hemodynamics, wake time, remifentanil dosage, and so on. At T0, T10, T13, and T14, TNF-α, IL-2, IL-10, MMP-9, and VEGF-C were measured. Compared with T0, the differences of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), matrix metallopeptidase 9 (MMP-9), and vascular endothelial growth factor-C (VEGF-C) in the two groups were statistically significant (p < 0.05). When compared to group C, VEGF-C in group E was reduced at T10 and T13 (p < 0.05). For both groups, there were intragroup differences in the changes of MMP-9 and VEGF-C levels (p < 0.05). Compared to group C, on the postoperative, group E exhibited a lower change rate of TNF-α and VEGF-C (p < 0.05). Perioperative application of esketamine in patients with lung cancer provided significant sedative and analgesic effects and affected cytokines in the tumor microenvironment.