Clinical characteristics and therapeutic effects of checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer.

BACKGROUND: With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects. METHODS: The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized. RESULTS: 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs. CONCLUSION: We found that glucocorticoid 1-2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.

Potential roles of vitamin D binding protein in attenuating liver injury in sepsis.

BACKGROUND: In sepsis, vitamin D binding protein (VDBP) has been shown to be low-expressed. The current study examined the relationship between serum VDBP level and liver injury in sepsis patients, as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide (LPS). METHODS: The human study included 78 sepsis patients and 50 healthy volunteers. Sepsis patients were categorized into sepsis survivor group (n = 43) and sepsis non-survivor group (n = 35) based on 28-day mortality for data analysis. Adult male C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Serum samples were collected on day 1, 3, 5 and 7 to determine the levels of VDBP, 25-hydroxyvitamin D [25(OH)D3], 1,25-dihydroxyvitamin D [1,25(OH)2D3], interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells. RESULTS: Serum levels of VDBP, 25(OH)D3, and 1,25(OH)2D3 were significantly lower in sepsis patients vs. the healthy control (P < 0.001), as well as in the sepsis non-survivor group vs. the sepsis survivor group (P < 0.001, P = 0.0338, or P = 0.0013, respectively). Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (r = - 0.2565, P = 0.0234) and Sequential Organ Failure Assessment score (r = - 0.3522, P = 0.0016), but lower serum albumin (ALB, r = 0.4628, P < 0.001) and total protein (TP, r = 0.263, P = 0.02). In CLP mice, there was a 5-day period of serum VDBP reduction, followed by return towards the baseline on day 7. VDBP was also decreased in LPS-treated THLE2 cells (P < 0.001). VDBP overexpression reduced LPS-induced THLE2 damage. Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway. CONCLUSION: VDBP may be protective against sepsis-induced liver injury.

Clinical analysis of 16 cases of pulmonary cryptococcosis in patients with normal immune function.

BACKGROUND: Pulmonary cryptococcosis (PC) is an invasive pulmonary fungal disease caused by Cryptococcus neoformans or Cryptococcus gattii. Cryptococcus is the opportunistic pathogen. Immune damage and chronic consumptive diseases are the high risk. The prevalence of cryptococcus infection is 5% to 10% in individuals with weakened immune function. In recent years, with the application of glucocorticoids, antitumor drugs, and broad-spectrum antibiotics, the prevalence of cryptococcal infection has increased yearly. Cryptococcus infection can also occur in normal people without underlying diseases. One in every 100,000 individuals with normal immune function is also affected, but these cases are often misdiagnosed due to inadequate understanding and low awareness of PC in individuals with normal immune function. In this study, we investigated the clinical characteristics of PC in patients with normal immune function to improve the diagnosis and treatment of these cases. METHODS: We retrospectively analyzed the clinical, imaging and pathological data of 16 patients with pulmonary cryptococcosis treated at Beijing Shijitan Hospital between 2010 and 2017. RESULTS: Of the 16 patients with disseminated cryptococcosis, 6 were men, and 10 were women; their ages were 35 to 76 years (median: 53 years). Initial symptoms were cough, sputum, chest pain, and fever. Thirteen patients had a history of chronic disease or tumor, including diabetes and bronchial asthma (n=2), simple hypertension (n=2), chronic bronchitis (n=2), diabetes and hypertension (n=5), previous tuberculosis (n=1), and previous lung cancer surgery (n=1). Chest computed tomography (CT) in these 16 patients showed single or multiple nodules and masses (n=14), lobar consolidation (n=1), and diffuse mixed lesions (n =1). Lung biopsy showed granulomatous lesions in these 16 patients. Cryptococcus neoformans was identified with Grocott's methenamine silver and Grocott's methenamine silver (GMS) stains. Fourteen patients received fluconazole alone; two patients with intracranial infection received fluconazole combined with amphotericin B. Five patients improved significantly, and nine patients improved with significant lesion absorption. CONCLUSIONS: The clinical manifestations of PC are nonspecific in patients with normal immune function. Lung biopsy and cryptococcus antigen tests of cerebrospinal fluid are valuable diagnostic aids. Fluconazole is an effective treatment for disseminated cryptococcal infection.

Recovery of tin from metal powders of waste printed circuit boards.

To avoid the adverse effects of tin on the smelting process used to recover copper from metal powders of waste printed circuit boards, an effective process is proposed that selectively extracts tin and its associated metals. That impacts of alkaline pressure oxidation leaching parameters on metal conversion were systematically investigated. The results showed that Sn, Pb, Al and small amounts of Zn in the metal powders were leached out, leaving copper residue. By optimizing the conditions, leaching recovery of 98.2%, 77.6%, 78.3 and 6.8% for Sn, Pb, Al and Zn, respectively, were achieved. Subsequently, more than 99.9% of Pb and Zn in the leaching solution were removed as a mixture of PbS-ZnS in the purification process, which can be used as a raw material in Pb smelting. Approximately 86.2% of Sn in the purified solution was recovered by electrowinning, and the purity of the cathode tin was over 99.8%.

Biological features of biofilm-forming ability of Acinetobacter baumannii strains derived from 121 elderly patients with hospital-acquired pneumonia.

This study is to investigate a biological activity of Acinetobacter baumannii isolates from sputum specimens of 121 elderly patients with hospital-acquired pneumonia. The ability of the isolates to form biofilms was quantitatively assessed by crystal violet staining, and adhesive property was examined using Giemsa staining. Biofilm-forming ability by the isolates was employed to test antimicrobial resistance and examine sources and clinical manifestations. The isolates grew as biofilm on abiotic surface at the indicated temperatures after a 48 h of incubation. 27.3 % of the isolates were strongly biofilm-positive in the samples, and 84.8 % displayed high adhesion ability (P < 0.05). All of the isolates showed antibiotic resistance at different levels, and the isolates produced strong biofilm exhibited low-level resistance to gentamicin, minocycline and ceftazidime (P < 0.05). The patients' experience in ICU, use of antibiotics and estimation of APACHE II (<17) were related to incidence of strong biofilm formation with no clinical manifestations found in the study. All clinical isolates are able to form biofilms which refer to adhesive efficiency and antibiotic resistance. Patient experiences in ICU surveillance, use of antibiotics and APACHE II scores are involved in biofilm-forming ability by the nosocomial pathogen derived from the hospitalized patients.

A retrospective analysis of carbapenem-resistant Acinetobacter baumannii-mediated nosocomial pneumonia and the in vitro therapeutic benefit of cefoperazone/sulbactam.

BACKGROUND: Acinetobacter baumannii has been reported increasingly as a significant causative organism of various nosocomial infections, including hospital-acquired pneumonia (HAP). The aim of this study was to investigate the clinical characteristics of HAP induced by carbapenem-resistant A. baumannii (CRAB) in elderly patients and the in vitro antimicrobial effects of cefoperazone/sulbactam combination therapy. METHODS: Seventy-one elderly patients in the geriatric ward of the General Hospital of the People's Liberation Army (PLAGH) with CRAB-induced HAP were analyzed retrospectively. The checkerboard method was used to determine the in vitro drug sensitivity of 60 CRAB strains to antimicrobial combinations (cefoperazone/sulbactam with meropenem, minocycline, or levofloxacin). The occurrence of carbapenemase genes was detected by PCR. RESULTS: CRAB-induced HAP occurred mostly in patients with underlying diseases. Prior to onset, most patients had received antimicrobial therapies including broad-spectrum ß-lactams, invasive mechanical ventilation, and catheterization. The 30-day survival rate was 95.1% in patients using cefoperazone/sulbactam, with or without combination with antimicrobial drugs, and 73.3% in patients not using cefoperazone/sulbactam (p<0.05). When cefoperazone/sulbactam was used in combination with minocycline, levofloxacin, and meropenem, minimum inhibitory concentrations MIC50 and MIC90 were reduced for each drug. The genes OXA-23 and OXA-51 were amplified in 96.7% of the strains, but the genes OXA-24, OXA-58, SIM, VIM, and IMP were not amplified. CONCLUSIONS: CRAB-induced HAP occurred mostly in patients with anemia or decreased levels of serum albumin, but with elevated levels of C-reactive protein and creatinine. Cefoperazone/sulbactam in combination with minocycline, meropenem, and levofloxacin had a synergistic and additive in vitro bacteriostatic action on CRAB.

Genome Sequence of Pseudomonas aeruginosa Strain LCT-PA41, with Changed Metabolism after Space Flight.

To explore the effects of space flight on microorganisms, Pseudomonas aeruginosa ATCC 27853 was sent into orbit for 398 h on the spacecraft ShenZhou VIII. Here, we present the draft genome sequence of the P. aeruginosa strain LCT-PA41, determined after space flight.