Atrial fibrillation in cancer, anticancer therapies, and underlying mechanisms.

Atrial fibrillation (AF) is a common arrhythmic complication in cancer patients and can be exacerbated by traditional cytotoxic and targeted anticancer therapies. Increased incidence of AF in cancer patients is independent of confounding factors, including preexisting myocardial arrhythmogenic substrates, type of cancer, or cancer stage. Mechanistically, AF is characterized by fast unsynchronized atrial contractions with rapid ventricular response, which impairs ventricular filling and results in various symptoms such as fatigue, chest pain, and shortness of breath. Due to increased blood stasis, a consequence of both cancer and AF, concern for stroke increases in this patient population. To compound matters, cardiotoxic anticancer therapies themselves promote AF; thereby exacerbating AF morbidity and mortality in cancer patients. In this review, we examine the relationship between AF, cancer, and cardiotoxic anticancer therapies with a focus on the shared molecular and electrophysiological mechanisms linking these disease processes. We also explore the potential role of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in the management of anticancer-therapy-induced AF.

Recombinant Slit2 attenuates tracheal fibroblast activation in benign central airway obstruction by inhibiting the TGF-ß1/Smad3 signaling pathway.

Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2-roundabout guidance receptor 1 (Slit2-Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-ß1 (TGF-ß1)-mediated airway fibrosis in vivo and in vitro. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-ß1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-ß1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-ß1 in RTFs via the TGF-ß1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2-Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.

Paxlovid reduces the 28-day mortality of patients with COVID-19: a retrospective cohort study.

PURPOSE: In this study, we aim to explore the efficacy of paxlovid on reducing mortality of COVID-19 patients in clinical setting, especially whether paxlovid modifies the risk of death in these severe and critical patients. METHODS: Our retrospective cohort study was conducted on the medical records of patients, consecutively admitted for COVID-19 to five hospitals in Chongqing, China from Dec 8, 2022 to Jan 20, 2023. Based on whether patients received paxlovid during their hospitalization, patients were grouped as paxlovid group and non-paxlovid group. We used 1:1 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between groups. Statistical analysis were performed by SPSS 23.0. The differences in 28-day mortality between these two groups and its influencing factors were the main results we focused on. RESULTS: There were 1018 patients included in our study cohort. With 1:1 ratio PSM, each of the paxlovid group and non-paxlovid group included 237 patients. The results showed that patients using paxlovid have a lower 28-day mortality in overall population either before PSM (OR 0.594, 95% CI 0.385-0.917, p = 0.019) or after PSM (OR 0.458, 95% CI 0.272-0.774, p = 0.003) with multivariable adjusted logistic regression models. Meanwhile, in severe subgroup, it showed similar findings.With paxlovid treatment, it showed a significantly lower 28-day mortality in severe subgroup both before PSM (28% vs.41%, p = 0.008) and after PSM (19% vs.32%, p = 0.007). CONCLUSION: Paxlovid can significantly reduce the risk of 28-day mortality in overall population and severe subgroup patients.This study distinguished the severe subgroup patients with COVID-19 who benefit more from paxlovid treatment.

Relationship between triglyceride-glucose index and blood eosinophils among asthmatic individuals in the USA.

BACKGROUND: Presently, the majority of investigations primarily evaluate the correlation between triglyceride-glucose index (TyGI) with lung diseases, such as asthma. However, they did not delve into the correlation between TyGI and inflammatory responses related to the disease. Few studies have explored the association between TyGI and blood eosinophil count (BEOC). Thus, National Health and Nutrition Examination Survey (NHANES) data were used in this study to evaluate the correlation between TyGI and BEOC in individuals with asthma. METHODS: This study investigated 3902 individuals with asthma. Linear regression analysis was performed to investigate the association between TyGI and BEOC in patients with asthma. Subsequently, the GAM and threshold effect models were used to validate the presence of either a nonlinear or linear association between TyGI and BEOC. Finally, stratified analyses were conducted to ascertain the correlations between different subgroups. RESULTS: Four linear regression models confirmed a positive linear correlation between TyGI and BEOC in patients with asthma. In Model D, which controlled for all covariates, BEOC increased by 12.44 cells/uL for every extra unit of TyGI. The GAM and threshold effect models further verified the positive linear correlation between TyGI and BEOC. The XGBoost model indicated that the six most significant variables influencing BEOC, in order of relative importance, were age, cholesterol level, body mass index (BMI), poverty-to-income ratio (PIR), BNEUC, and TyGI. CONCLUSIONS: In patients with asthma, the study discovered a linear positive correlation between TyGI and BEOC. This indicates a potential connection between TyGI and alterations in the immune status of individuals with asthma, which may help detect abnormalities in a timely manner and provide a reference for clinical decision-making. This study offers fresh insights for the future exploration of the management and treatment of asthma.

Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis.

INTRODUCTION: Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting ß2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD. METHODS: Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke. RESULTS: A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6% versus 1.3%; relative risk 1.42, 95% CI 1.11-1.81) and triple therapy (1.6% versus 1.4%; relative risk 1.29, 95% CI 1.03-1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was >1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power. CONCLUSION: Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of >1% per year.

GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts.

Benign tracheobronchial stenosis (BTS) is a fatal and incurable disease. Epithelial repair and matrix reconstruction play an important role in the wound repair process. If the interstitial context is not restored and stabilized in time, it can lead to pathological fibrosis. Here we attempted to identify cytokines that are involved in promoting wound repair. Growth differentiation factor 15 (GDF15) is a cytokine secreted by tracheal epithelial cells, which is indispensable for the growth of epithelial cells and inhibits the overgrowth of fibroblasts. GDF15 can counteract transforming growth factor-ß (TGFß1) stimulation of epithelial-mesenchymal transition (EMT) in tracheal epithelial cells and inhibit fibroblast activation via the TGFß1-SMAD2/3 pathway. In a rat model of tracheal stenosis, GDF15 supplementation alleviated the degree of tracheal stenosis. These results suggest that GDF15 prevents fibroblast hyperactivation and promotes epithelial repair in injured trachea. GDF15 may be a potential therapy to improve benign tracheobronchial stenosis.

Evaluation of Transbronchial Lung Cryobiopsy Freezing Time, Biopsy Size, Histological Quality, and Incidence of Complication: A Prospective Clinical Trial.

BACKGROUND: Transbronchial cryobiopsy (TBCB), a novel way of obtaining a specimen of lung tissue using a flexible cryoprobe, can obtain large lung biopsies without crush artifacts. The freezing time of TBCB was empirically selected from 3 to 7 s in the previous studies. However, no consensus has yet been reached regarding the optimal freezing time used in TBCB. OBJECTIVES: The primary endpoint was biopsy size in different freezing times. The secondary endpoints included sample histological quality, diagnostic confidence, and complications in different freezing times. METHODS: Patients who were suspected of DPLD requiring histopathological examination for further evaluation were enrolled in this study. Distinct biopsies were obtained by using different freezing times increased from 3 to 6 s sequentially. Samples were reviewed by 2 external expert pathologists. RESULTS: A total of 33 patients were enrolled, and 143 transbronchial cryobiopsies were taken in this trial. An average of 4.33 samples were taken from each patient. The mean biopsy size of different freezing times from 3 to 6 s was 9.10 ± 4.37, 13.23 ± 5.83, 16.26 ± 5.67, and 18.83 ± 7.50 mm2, respectively. A strong correlation between freezing time and biopsy size was observed (r = 0.99, p < 0.01). Statistically significant difference of biopsy size was detected in the freezing time of 3 s versus 4 s (p < 0.01) and 4 s versus 5 s (p = 0.02), but not in the freezing time of 5 s versus 6 s (p = 0.10). Overall bleeding in different freezing times from 3 to 6 s was 53.33%, 67.50%, 89.47%, and 77.14%, respectively. A significantly higher overall bleeding was observed when the freezing time exceeded 4 s (RR = 1.67, p < 0.01). Pneumothorax occurred in 4 cases (12.12%). One lethal case (3.03%) was noted 25 days after TBCB. Lung parenchyma was preserved well in all cryobiopsy samples. Thirty-one (93.94%) patients' histopathological findings were identified as sufficient to establish a CRP diagnosis. There was no statistical difference in diagnostic confidence between different freezing times. CONCLUSION: A longer freezing time was associated with a larger size of the biopsy sample but a higher risk of bleeding. The optimal transbronchial cryobiopsy freezing time is 3-4 s, which is easily achievable and provides an adequate biopsy size whilst creating a safety threshold from complications.

The prevalence and risks of major comorbidities among inpatients with pulmonary tuberculosis in China from a gender and age perspective: a large-scale multicenter observational study.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

Effect of rebiopsy methods and clinical features on T790M mutation after first-line EGFR-TKI treatment failure.

Aim: This study investigated the association between clinical data and T790M mutation in rebiopsy after EGFR tyrosine kinase inhibitors (EGFR-TKIs) failure, and explored the prognosis of T790M-positive patients. Methods: Patients with non-small-cell lung cancer undergoing rebiopsy after first-generation TKI failure were reviewed. Results & conclusion: Patients with brain metastases, negative TP53, initial 19del and longer initial PFS had higher positive rate of T790M. The median progression-free survival (PFS) of T790M-positive patients with cytology and tissue rebiopsy were longer than patients with liquid rebiopsy. The median PFS of T790M-positive patients rebiopsied by ordinary bronchoscope and endobronchial ultrasound-guided transbronchial lung biopsy with a guided sheath (EBUS-GS-TBLB) were longer than that of the patients rebiopsied by EBUS transbronchial needle aspiration (TBNA).

Lay abstract A specific genetic mutation, T790M, is the main cause of drug resistance in patients with lung cancer receiving a type of drug called EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib. We explored the factors that influence the prognosis of T790M-positive patients and how this mutation causes resistance. We found a number of biomarkers that are linked to higher expression of T790M, including brain metastases and longer initial treatment period of EGFR-TKI. The median length of time before tumors started progressing in T790M-positive patients who underwent cytology and tissue rebiopsy was longer than patients who received a blood biopsy. The length of time before progression in patients undergoing different rebiopsy methods (such as ordinary bronchoscope and endobronchial ultrasound bronchoscope) was different.

Left Main Bronchus Stenosis Lesion, Neutrophil Count, and Platelet Count Are Predictors of Post-Tuberculosis Bronchomalacia.

BACKGROUND Post-tuberculosis bronchomalacia (PTBM) is one of the main conditions occurring in patients after tracheobronchial tuberculosis (TBTB), and is also associated with the recurrence of symptoms. The present study aimed to investigate the predictors of PTBM in patients who had been undergoing appropriate TB treatment. MATERIAL AND METHODS Clinical data of 104 patients with symptomatic airway stenosis after TBTB between January 01, 2019 and June 31, 2020 were recorded and analyzed. The association between baseline clinical characteristics, laboratory results, and PTBM was calculated with logistical regression. The time from onset of bronchoscopic intervention was examined by Kaplan-Meier estimates; differences between the 2 groups were tested by the log-rank test. RESULTS Fifty-seven patients (54.81%) had PTBM. In the multivariate logistical analysis, the left main bronchus stenosis lesion (odds ratio [OR]=3.763), neutrophil (NEUT) count (OR=1.527), and platelet (PLT) (OR=1.010) count were predictors of PTBM. During follow-up, patients with BM had a significantly longer duration from onset of bronchoscopic intervention than patients without BM (hazard ratio=2.412, P<0.0001). Further, all patients needing long-term bronchoscopic intervention therapy were subsequently identified as having PTBM. Additionally, blood PLT counts were significantly decreased to normal levels in the non-BM group (P<0.05), but not in the BM group (P>0.05). CONCLUSIONS PTBM is most likely to occur in the left main bronchus. The inflammatory and immune responses associated with NEUT and PLT may represent therapeutic targets of PTBM. Our study is the first to report that decreased blood PLT count has the potential to monitor the treatment response.

Specific Lung Squamous Cell Carcinoma Prognosis-Subtype Distinctions Based on DNA Methylation Patterns.

BACKGROUND Lung squamous cell carcinoma (LUSC) is one of the major types of non-small-cell lung cancer. Epigenetic alterations, such as DNA methylation, have been recognized to be closely associated with the tumorigenesis and progression. MATERIAL AND METHODS In this study, we investigated the prognosis subgroups and assessed their correlation with clinical characteristics in LUSC using a methylation array acquired from The Cancer Genome Atlas (TCGA) database. RESULTS A total of 196 DNA methylation sites exhibited a significant association with patient prognosis, and patients were further stratified into 7 prognosis subgroups based upon the consensus clustering. The patients in every subgroup were different in terms of prognosis and TNM stage. In addition, we found these 196 significant methylation sites corresponded to 258 genes. The function enrichment analysis revealed that these 258 genes enriched in biological pathways were closely related to cancers, such as DNA methylation and demethylation, cell cycle DNA replication, regulation of signal transduction by p53 class mediator, and genetic imprinting. Subsequently, we determined the levels of methylation sites in 7 subgroups, and found 24 intra-subgroup-specific methylation sites. Meanwhile, we selected 3 subgroups-specific methylation sites to construct the prognosis model for LUSC patients using multivariate Cox proportional risk regression model analysis. This model can effectively predict the prognosis of LUSC patients. CONCLUSIONS Our study identified a new classification of LUSC into 7 prognosis subgroups on the basis of DNA methylation data in TCGA, which demonstrated that molecular subtypes are independent factor for prognosis in LUSC. This may provide a more detailed explanation for LUSC heterogeneity. Additionally, this classification will contribute to discovery of new biomarkers of LUSC and provide more accurate subdivision of LUSC. Furthermore, these specific DNA methylation sites and corresponding genes can serve as biomarkers for early diagnosis, accurate therapy, and prognosis prediction.

A Large Central Bronchopleural Fistula Closed by Bronchoscopic Administration of Recombinant Bovine Basic Fibroblast Growth Factor: A Case Report.

A large central bronchopleural fistula (BPF) surrounded by mediastinal tissue was successfully closed by local administration of recombinant bovine basic fibroblast growth factor (rbFGF) using the bronchoscope. No complications were observed during and after this bronchoscopic treatment. This is the first report of the bronchoscopic treatment of a large central BPF by the local spray of rbFGF. The bronchoscopic treatment with rbFGF is a potentially cost-effective method for central BPF surrounded by mediastinal tissue.

Endobronchial closure of the bronchopleural fistula with the ventricular septal defect occluder: a case series.

OBJECTIVES: The ventricular septal defect (VSD) occluder has been reported to be a novel method for the closure of bronchopleural fistula (BPF). Our study was to confirm the use of VSD occluder in treating BPF after pneumonectomy or lobectomy. METHODS: We performed a single-center, retrospective study of 10 consecutive patients (8 men and 2 women aged 29-70 years) with postoperative BPF receiving the VSD occluder treatment. We used the HeartR™ Membranous VSD occluder (Lifetech Scientific Co., Shenzhen, China) for the closure of BPF through flexible bronchoscopy under general anesthesia. Demographic characteristics, BPF characteristics, and clinical outcomes were collected from patients' files using the standardized data abstraction forms. RESULTS: The underlying diseases were lung cancer in 6 patients, pulmonary tuberculosis in 3, and bronchiectasis in 1. Right-sided BPFs occurred in 6 patients, and left-sided BPFs occurred in 4. Five patients were underweight with a body mass index < 18.5 kg/m2. The VSD was placed in all 10 patients with a 100% technical success rate and a 70% complete closure rate during follow-up with no complications, on a median follow-up period of 115 days (range 46-975 days). In 1 patient, the VSD occluder was reinstalled with complete closure; in 1 and 2 patients with underweight and chronic empyema, the VSD occluders partially and completely failed with good physical tolerance, respectively. CONCLUSIONS: Our study demonstrated the bronchoscopic closure of BPF after lung resection using the VSD occluder is an off-label but safe and effective method. We prefer to stabilize the BPF by eradicating the underlying diseases and providing nutritional support to those receiving VSD occluder closure treatment.

Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID-19 in Chongqing.

Mortality is high among severe patients with 2019 novel coronavirus-infected disease (COVID-19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID-19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate ≥30 breaths/min, (b) blood oxygen saturation ≤93%, and (c) PaO2 /FiO2 ≤ 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3-6.0). Pulmonary inflammation index, platelet counts, sodium, C-reactive protein, prealbumin, and PaCO2 showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] ≥ 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7-0.8). And potassium, creatinine, temperature, and D-dimer showed mild distinguishing power (each AUC between 0.6-0.7). In addition, higher C-reactive protein was associated with shorter time to progress to severe cases (r = -0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID-19.

Inactivation of ADAMTS18 by aberrant promoter hypermethylation contribute to lung cancer progression.

Lung cancer is the most frequently diagnosed cancer worldwide. Epigenetic regulation contributes to lung cancer pathogenesis. The ADAMTS18 tumor suppressor gene is inactivated in some cancers, but its involvement in lung cancer has not been shown. Immunohistochemistry, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and methylation-specific PCR were used to assay ADAMTS18 expression and promoter methylation in lung tumor tissues and adjacent tissues. Cell viability, transwell, and wound-healing assays, as well as flow cytometry were used to characterize the biological activity of ADAMTS18. The influence of ADAMTS18 on protein expression was assayed using western blots analysis, and its effect on chemosensitivity was assayed by the response to cisplatin. We found that ADAMTS18 was silenced in lung cancer cells by promoter methylation. Demethylation by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, with or without the histone deacetylase inhibitor trichostatin A, restored ADAMTS18 expression. Compared with normal lung tissue, ADAMTS18 in lung tumors was frequently methylated. Overexpression of ADAMTS18 in lung cancer cells inhibited cell proliferation, migration, and invasiveness and induced G0/G1 cell cycle arrest. Furthermore, ADAMTS18 suppressed epidermal growth factor receptor/protein kinase B (EGFR/AKT) signaling, which sensitized lung cancer cells to cisplatin. Thus, our results demonstrated that the tumor suppressor gene ADAMTS18 was downregulated in lung cancer by promoter CpG methylation, and it promoted sensitivity to cisplatin via EGFR/AKT signaling. Our study suggests that ADAMTS18 promoter methylation is a potential epigenetic biomarker for early detection of lung cancer and warrants investigation as a therapeutic target for early-stage lung cancer.

PARP inhibitors synergize with gemcitabine by potentiating DNA damage in non-small-cell lung cancer.

Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise in the treatment of patients with deficiencies in homologous recombination (HR) DNA repair, such as those with loss of BRCA1 or BRCA2 function. However, emerging studies suggest that PARP inhibition can also target HR-competent cancers, such as non-small-cell lung cancer (NSCLC), and that the therapeutic effect of PARP inhibition may be improved by combination with chemotherapy agents. In our study, it was found that PARP inhibitors talazoparib (BMN-673) and olaparib (AZD-2281) both had synergistic activity with the common first-line chemotherapeutic gemcitabine in a panel of lung cancer cell lines. Furthermore, the combination demonstrated significant in vivo antitumor activity in an H23 xenograft model of NSCLC compared to either agent as monotherapy. This synergism occurred without loss of HR repair efficiency. Instead, the combination induced synergistic single-strand DNA breaks, leading to accumulation of toxic double-strand DNA lesions in vitro and in vivo. Our study elucidates the underlying mechanisms of synergistic activity of PARP inhibitors and gemcitabine, providing a strong motivation to pursue this combination as an improved therapeutic regimen.

GYY4137 attenuates LPS-induced acute lung injury via heme oxygenase-1 modulation.

GYY4137, a slow-releasing hydrogen sulfide (H2S) donor, has been reported to exert anti-inflammatory activity and protect against sepsis. Heme oxygenase-1 (HO-1) is an important anti-inflammatory heat shock protein and plays a similar effect on sepsis. This study investigated the role of GYY4137 in acute lung injury (ALI) via HO-1 regulation. Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide (LPS) and the mechanism of anti-inflammatory effects of GYY4137 was investigated in mice and RAW264.7 cells. GYY4137 reduced the LPS-mediated pulmonary injury and neutrophil infiltration, and inhibited the LPS-induced production of proinflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Moreover, GYY4137 suppressed the LPS-evoked NF-κB activation in RAW264.7 cells. GYY4137, not time-expired GYY4137 significantly induced HO-1 expression compared with the LPS group. The beneficial effects of GYY4137 above were reversed by the HO-1 inhibitor tin protoporphyrin (SnPP). These results suggest an anti-inflammatory effect and a therapeutic role of GYY4137 in LPS-induced ALI via HO-1 regulation.

A multicenter RCT of noninvasive ventilation in pneumonia-induced early mild acute respiratory distress syndrome.

RATIONALE: Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with "early" stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). OBJECTIVES: To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. METHODS: Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. RESULTS: Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005-1.379], p = 0.043). CONCLUSIONS: Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. TRIAL REGISTRATION: NCT01581229 . Registered 19 April 2012.

Primary Tracheal Mucosa-Associated Lymphoid Tissue Lymphoma Treated with a Water-Jet Hybrid Knife: A Case Report.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the trachea is very rare and is easily misdiagnosed as a bronchogenic carcinoma or benign tracheal tumor. Here, we report a clinical case where a new clinical approach involving a water-jet hybrid knife was employed in the diagnosis and treatment of primary tracheal MALT lymphoma.

Interventional Bronchoscopy for the Treatment of Malignant Central Airway Stenosis: An Expert Recommendation for China.

Malignant central airway stenosis refers to airway stenosis caused by primary or metastatic malignant tumors which may lead to different levels of dyspnea or asphyxia in patients. With the rapid development of interventional pulmonology, therapeutic bronchoscopy has become one of the main methods for the diagnosis and treatment of malignant central airway stenosis. However, the level of diagnosis and treatment of respiratory intervention techniques in China is uneven at present, the treatment methods are not uniform, the treatment effects vary greatly, and some treatments even lead to serious complications. The interventional treatment technology for malignant central airway stenosis in China needs to be standardized. Therefore, the relevant experts of the Beijing Health Promotion Association Respiratory and Oncology Intervention and Treatment Alliance have formulated this consensus after several rounds of full discussion.