Chemoradiotherapy versus radiotherapy in high risk salivary gland cancer.

OBJECTIVE: The aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables. METHODS: Patients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model. RESULTS: A total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36-4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17-3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT. CONCLUSION: Adjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC.

Laboratory and field evaluation of a low-cost optical particle sizer.

Low-cost sensors are widely used to collect high-spatial-resolution particulate matter data that traditional reference monitoring devices cannot. In addition to the mass concentration, the number concentration and size distribution are also fundamental in determining the origin and hazard level of particulate pollution. Therefore, low-cost optical sensors have been improved to establish optical particle sizers (OPSs). In this study, a low-cost OPS, the Nova SDS029, is introduced, and it is evaluated in comparison to two reference instruments-the GRIMM 11-D and the TSI 3330. We first tested the sizing accuracy using polystyrene latex spheres. Then, we assessed the mass and number size distribution accuracy in three application scenarios: indoor smoking, ambient air quality, and mobile monitoring. The evaluations suggest that the low-cost SDS029 rivals research-grade optical sizers in many aspects. For example, (1) the particle diameters obtained with the SDS029 are close to the reference instruments (usually < 10%) in the 0.3-5 µm range; (2) the number of particles and mass concentration are highly correlated (r ≥ 0.99) with the values obtained with the reference instruments; and (3) the SDS029 slightly underestimates the number concentration, but the derived PM2.5 values are closer to monitoring station than the reference instruments. The successful application of the SDS029 in multiple scenarios suggests that a plausible particle size distribution can be obtained in an easy and cost-efficient way. We believe that low-cost OPSs will increasingly be used to map the sources and risk levels of particles at the city scale.

Evaluating the performance and influencing factors of three portable black carbon monitors for field measurement.

Black carbon (BC) is associated with adverse human health and climate change. Mapping BC spatial distribution imperatively requires low-cost and portable devices. Several portable BC monitors are commercially available, but their accuracy and reliability are not always satisfactory during continuous field observation. This study evaluated three models of portable black carbon monitors, C12, MA350 and DST, and investigates the factors that affect their performance. The monitors were tested in urban Beijing, where portable devices running for one month alongside a regular-size reference aethalometer AE33. The study considers several factors that could influence the monitors' performance, including ambient weather, aerosol composition, loading artifacts, and built-in algorithms. The results show that MA350 and DST present considerable discrepancies to the reference instrument, mainly occurring at lower concentrations (0-500 ng/m3) and higher concentrations (2500-8000 ng/m3), respectively. These discrepancies were likely caused by the anomalous noise of MA350 and the loading artifacts of DST. The study also suggests that the ambient environment has limited influence on the monitors' performance, but loading artifacts and accompanying compensation algorithms can result in unrealistic data. Based on the evaluation, the study suggests that C12 is the best choice for unsupervised field measurement, DST should be used in scenarios where frequent maintenance is available, and MA350 is suitable for research purposes with post-processing applicable. The study highlights the importance of assigning portable BC monitors to appropriate applications and the need for optimized real-time compensation algorithms.

l-lactic acidosis confers insensitivity to PKC inhibitors by competing for uptake via monocarboxylate transporters.

Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non-small cell lung cancer cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, none of the PKC inhibitors has been approved for anticancer therapy yet due to the limited efficacy in clinical trials, and the underlying mechanisms remain unclear. l-lactic acidosis, a common condition comprising high l-lactate concentration and acidic pH in the tumor microenvironment, has been known to induce tumor metastasis and drug resistance. In this study, l-lactic acid was found to reverse the inhibitory effects of pan-PKC inhibitors GO6983 on PKC activity, cell migration, and EGFR-TKI resistance, but these effects were not affected by the modulators of lactate receptor GPR81. Interestingly, blockade of lactate transporters, monocarboxylate transporter-1 and -4 (MCT1 and MCT4), attenuated the intracellular level of GO6983, and its inhibitory effect on PKC activity, suggesting that lactic acid promotes the resistance to PKC inhibitors by competing for the uptake through these transporters rather than by activating its receptor, GPR81. Our findings explain the underlying mechanisms of the limited response of PKC inhibitors in clinical trials.

Persistent pollution of genetic materials in a typical laboratory environment.

From the onset of coronavirus disease (COVID-19) pandemic, there are concerns regarding the disease spread and environmental pollution of biohazard since studies on genetic engineering flourish and numerous genetic materials were used such as the nucleic acid test of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). In this work, we studied genetic material pollution in an institute during a development cycle of plasmid, one of typical genetic materials, with typical laboratory settings. The pollution source, transmission routes, and pollution levels in laboratory environment were examined. The Real-Time quantitative- Polymerase Chain Reaction results of all environmental mediums (surface, aerosol, and liquid) showed that a targeted DNA segment occurred along with routine experimental operations. Among the 79 surface and air samples collected in the genetic material operation, half of the environment samples (38 of 79) are positive for nucleic acid pollution. Persistent nucleic acid contaminations were observed in all tested laboratories and spread in the public area (hallway). The highest concentration for liquid and surface samples were 1.92 × 108 copies/uL and 5.22 × 107 copies/cm2, respectively. Significant amounts of the targeted gene (with a mean value of 74 copies/L) were detected in the indoor air of laboratories utilizing centrifuge devices, shaking tables, and cell homogenizers. Spills and improper disposal of plasmid products were primary sources of pollution. The importance of establishing designated experimental zones, employing advanced biosafety cabinets, and implementing highly efficient cleaning systems in laboratories with lower biosafety levels is underscored. SYNOPSIS: STATEMENT. Persistent environmental pollutions of genetic materials are introduced by typical experiments in laboratories with low biosafety level.

The Contribution of Double-strand Break Repair Radiation Sensitive Protein 51 Genotypes to Lung Cancer in Taiwan.

BACKGROUND/AIM: Numerous studies have reported the over-expression of the radiation-sensitive protein 51 (RAD51) in various types of cancer. However, the role of RAD51 genotypes in lung cancer remains largely unknown. This study aimed to assess the impact of the common variant RAD51 rs1801320 (G-135C) genotypes on the risk of lung cancer in Taiwan. MATERIALS AND METHODS: The contribution of RAD51 rs1801320 genotypes to lung cancer risk was investigated in a cohort comprising 358 lung cancer patients and 716 age- and sex-matched healthy controls, utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The analysis revealed that among the control subjects, the percentages of GG, CG, and CC genotypes of RAD51 rs1801320 were 73.2%, 24.3%, and 2.5%, respectively. Among the lung cancer patients, these percentages were 71.0%, 25.1%, and 3.9%, respectively (p for trend=0.4075). Allelic frequency distributions showed no significant association between the C allele of RAD51 rs1801320 and lung cancer risk determination (p=0.2987). Specifically, the RAD51 rs1801320 CC genotypes were associated with an elevated risk of lung cancer among males [adjusted odds ratio (aOR)=2.28, 95% confidence interval (95%CI)=1.03-4.87] and smokers (aOR=2.93, 95%CI=1.23-5.87), but not among females and non-smokers. CONCLUSION: The RAD51 rs1801320 CC genotype was identified as a risk factor for elevated lung cancer risk in males and smokers. This genotype may serve as a molecular biomarker at the DNA level for early detection and prediction of lung cancer in Taiwan.

Comparative efficacy and safety of non-polymyxin antibiotics against nosocomial pneumonia, complicated intra-abdominal infection, or complicated urinary tract infection: A network meta-analysis of randomised clinical trials.

OBJECTIVES: The increasing epidemic of infections caused by drug-resistant Gram-negative bacteria has led to the development of several antibiotic therapies. Owing to the scarcity of head-to-head comparisons of current and emerging antibiotics, the present network meta-analysis aimed to compare the efficacy and safety of antibiotics in patients with nosocomial pneumonia, complicated intra-abdominal infection, or complicated urinary tract infection. METHODS: Two independent researchers systematically searched databases up to August 2022 and included 26 randomised controlled trials that fulfilled the inclusion criteria. The protocol was registered in the Prospective Register of Systematic Reviews, PROSPERO (CRD42021237798). The frequentist random effects model (R version 3.5.1, netmeta package) was utilized. The DerSimonian-Laird random effects model was used to estimate heterogeneity. The calculated P-score was applied to rank the interventions. Additionally, inconsistencies, publication bias, and subgroup effects were assessed in the present study to avoid bias. RESULTS: There was no significant difference among included antibiotics in terms of clinical response and mortality, probably because most antibiotic trials were designed to be non-inferior. In terms of P-score ranking, carbapenems may be the recommended choice considering both adverse events and clinical responses. On the other hand, for carbapenem-sparing options, ceftolozane-tazobactam was the preferred antibiotic for nosocomial pneumonia; eravacycline, for complicated intra-abdominal infection; and cefiderocol, for complicated urinary tract infection. CONCLUSION: Carbapenems may be preferable options in terms of safety and efficacy for the treatment of Gram-negative bacterial complicated infections. However, to preserve the effectiveness of carbapenems, it is important to consider carbapenem-sparing regimens.

Bevacizumab versus Ramucirumab in EGFR-Mutated Metastatic Non-Small-Cell Lung Cancer Patients: A Real-World Observational Study.

The combination of bevacizumab or ramucirumab with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, or immunotherapy for non-small-cell lung cancer (NSCLC) patients with EGFR mutations could have survival benefits. However, no study, to date, has been conducted to compare the efficacy and safety of these two antiangiogenic therapies (AATs). Stage IIIB to IV EGFR-mutated NSCLC patients who received first-line EGFR-TKIs between January 2014 and May 2022 were enrolled. These patients were divided into two groups: those receiving bevacizumab and those receiving ramucirumab as a combination therapy in any line of treatment. Ninety-six patients were enrolled in this study's final analysis. The progression-free survival (PFS) of patients who received front-line AATs combined with EGFR-TKI therapy was longer than that of patients receiving later-line AATs combined with other therapies (19.6 vs. 10.0 months, p < 0.001). No difference in overall survival (OS) was observed between front-line and later-line therapy (non-reach vs. 44.0 months, p = 0.261). Patients who received these two different AATs did not differ in PFS (24.1 vs. 15.7 months, p = 0.454) and OS (48.6 vs. 43.0 months, p = 0.924). In addition, these two AATs showed similar frequencies of the T790M mutation (43.6% vs. 38.2%; p = 0.645). Multivariate Cox regression analysis indicated several AAT cycles as an independent good prognostic factor in OS. The incidence of some adverse events such as bleeding and hepatitis was higher for bevacizumab than for ramucirumab but it was not significant. Front-line AAT and EGFR-TKI combination therapy improved the PFS of stage IV EGFR-mutated NSCLC patients. The effectiveness and safety of the two AATs were similar.

Mortality and ventilator dependence in critically ill patients with ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a key pathogen associated with ventilator-associated pneumonia (VAP). Research on treatment outcomes, especially ventilator dependence, in patients with VAP caused by CRAB remains limited. METHODS: This retrospective multicenter study included ICU-admitted patients with VAP caused by CRAB. The original cohort was included as the mortality evaluation cohort. The ventilator dependence evaluation cohort included cases that survived more than 21 days after VAP and without prolonged ventilation before VAP onset. The mortality rate, ventilator dependence rate, clinical factors associated with treatment outcomes, and treatment outcome differences with various VAP onset times were investigated. RESULTS: In total, 401 patients with VAP caused by CRAB were analyzed. The 21-day all-cause mortality rate was 25.2%, and the 21-day ventilator dependence rate was 48.8%. Clinical factors associated with 21-day mortality included lower body mass index, higher sequential organ failure assessment score, vasopressors usage, CRAB persistence, and VAP onset time > seven days. Clinical factors associated with 21-day ventilator dependence included older age, vasopressors usage, and VAP onset time > seven days. CONCLUSIONS: ICU-admitted patients with CRAB-related VAP had high mortality and ventilator dependence rates. Older age, vasopressor usage, and longer VAP onset time were independent factors associated with ventilator dependence.

Urban Low-Rise Residential Areas Provide Preferred Song Post Sites for a Resident Songbird.

Urbanization is expanding rapidly worldwide, and brings additional selection pressure on animals. The song differences between urban and rural songbirds have been widely verified, but the effects of urban morphological variation on long-settled urban birds have been poorly explored. Here, we investigated the distribution and song differences of a common resident songbird-the oriental magpie-robin (Copsychus saularis) between three urban morphology types (i.e., urban park, low-rise residential area, and high-rise residential area). The results indicated that the population density in low-rise residential areas was significantly higher than in urban parks, while it was the lowest in high-rise residential areas. Males in low-rise residential areas had greater song length, syllable numbers, frequency bandwidth, and song diversity than those in urban parks. The song differences were mainly related to habitat types, independent of singing height and perch type. Our findings suggest that low-rise residential areas may provide preferred song post sites for the oriental magpie-robin, which is well-adapted to the low-rise building morphology, but rejects the emerging high-rise buildings. Future studies are needed to assess the effects of urban morphological variation on more resident animals to determine which urban morphologies are conducive to enhancing biodiversity and encouraging animals to settle in urban areas.

Dynamic variations of phthalate esters in PM2.5 during a pollution episode.

Phthalate esters (PAEs) as hazardous air pollutants can be easily released during the life cycle of plastic products. In this study, a thermal desorption aerosol comprehensive two-dimensional gas chromatography mass spectrometer coupled with a dual-trap was developed and used to measure the hourly-resolved PAEs characteristics in atmospheric PM2.5 at an urban site. Dimethyl phthalate (DMP), diethyl (DEP), dibutyl (DnBP), benzyl butyl (BBP), di(2-ethylhexyl) (DEHP), and di-n-octyl phthalate (DnOP) in PM2.5 were analyzed. The most abundant compounds were DEHP and DMP, followed by DnBP and DEP. The mass concentrations of the detected PAEs are comparable to those at other urban sites measured using offline methods with a lower time resolution. The concentrations of PAEs showed intense change with the variation of PM2.5 mass concentration. The proportion of DEHP increased while that of DMP decreased with the increase in PM2.5 pollution. Positive correlations between PAEs and PM2.5, organic carbon, and elemental carbon were observed, while PAEs had negative correlation with the ambient temperature. Our observation provides evidences on understanding the volatile and semi-volatile PAEs in the ambient aerosols.

Evaluation of a cost-effective roadside sensor platform for identifying high emitters.

High-emission vehicles (high emitters) likely have significantly higher nitrogen oxide and particle number (PN) emission factors compared to other vehicles. Effective identification of these vehicles in road traffic requires efficient and cost-effective instruments. In this study, a compact, cost-effective sensor platform was developed and evaluated in a field experiment. The platform was deployed on a roadside, and we measured pollutant concentrations in the exhaust plumes of four diesel trucks with various aftertreatment systems, cargo loads, and driving speeds. The sensor platform successfully measured carbon dioxide, PN, and nitric oxide (NO) concentrations, and the data were used to derive the plume-based emission factors of these pollutants. By considering both NO and PN emission factors, three diesel trucks with failed or outdated aftertreatment systems were successfully identified as potential high emitters. The NO emission factor obtained by the sensor platform was consistent with that of the benchmark portable emission measurement system. The sensor platform also effectively elucidated the differential influences of aftertreatment systems and driving conditions on emission factors. This pilot test demonstrates the feasibility of a sensor-based system for high emitter identification. Owing to its cost-effective and compact design, the proposed sensor platform has greater potential for mass networked deployment than regular-size instruments, thereby effectively supporting regulatory protocols for screening high emitters on public roads.

The Feasibility of Interventional Pulmonology Methods for Detecting the T790M Mutation after the First or Second-Generation EGFR-TKI Resistance of Non-Small Cell Lung Cancer.

The development of third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) targeting T790M-mutant non-small cell lung cancer (NSCLC) has raised the importance of re-biopsy after EGFR-TKI failure. This study aimed to investigate the feasibility of interventional pulmonology (IP) procedures as re-biopsy methods for identifying the T790M mutation in EGFR-TKI-resistant patients. One hundred and thirty-nine NSCLC patients who underwent IP procedures for re-biopsy as their initial investigation after EGFR-TKI treatment failure were enrolled in this study between January 2020 and August 2022. All patients underwent a first re-biopsy with IP methods, with a diagnostic yield of 81.2% and T790M mutation detection rate of 36%. Thirty patients underwent a second re-biopsy; IP methods were used for 17 (56.6%) patients and non-IP methods for 13 (43.4%) patients; the T790M mutation detection rate was 36.4%. Only six patients underwent a third re-biopsy; no T790M mutation was noted. The T790M mutation detection rate did not differ between IP and non-IP methods (33.6 % vs. 37.5%, p = 0.762). In 11 cases (7.5%), a re-biopsy revealed histologic transformation from lung adenocarcinoma. IP procedures, as first-line re-biopsy methods for NSCLC, are feasible and provide sufficient tissue for identification of the resistance mechanism and target gene T790M mutation.

Association of Interleukin-8 Promoter Genotypes With Taiwan Lung Cancer Risk.

BACKGROUND/AIM: Chronic inflammation is believed to play a critical role in the pathogenesis of lung cancer. Interleukin-8 (IL-8) is an inflammatory cytokine and plays an important role in cancer development. Few studies have investigated the association between interleukin-8 - 251T/A (rs4073) genotype and lung cancer risk in various populations. MATERIALS AND METHODS: In the current study, genotypes of interleukin-8 rs4073 were analyzed in 358 lung cancer patients and 716 healthy controls in Taiwan, by the PCR-RFLP methodology. RESULTS: The distribution frequencies of interleukin-8 rs4073 genotypes between control and case groups were compared, and the homozygous variant AA genotypes showed a lower percentage in the case group compared to the control group (OR=0.57, 95%CI=0.39-0.85, p=0.0059). The distributions of alleles frequencies also exhibited statistical difference (p=0.0066). There was an interaction between interleukin-8 rs4073 and smoking habits (p=0.0051). CONCLUSION: Interleukin-8 rs4073 genotypes were associated with lung cancer susceptibility, especially for smokers.

The optimal therapy strategy for epidermal growth factor receptor-mutated non-small cell lung cancer patients with brain metastasis: A real-world study from Taiwan.

BACKGROUND: The treatment options for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with brain metastases (BMs) include EGFR-tyrosine kinase inhibitors (TKIs), stereotactic radiosurgery (SRS), whole-brain radiotherapy, brain surgery, and antiangiogenesis therapy. As treatment options evolve, redefining optimal treatment strategies to improve survival are crucial. METHODS: A total of 150 EGFR-mutant NSCLC patients with BMs who received first- or second-generation EGFR-TKIs as first-line treatment between January 2012 and October 2019 were included in this analysis. RESULTS: After multivariate analysis, patients with the graded prognostic assessment for lung cancer using molecular markers (Lung-mol GPA) ≥3 (hazard ratio [HR]: 0.538, 95% confidence interval [CI]: 0.35-0.83), who received afatinib or erlotinib as first-line treatment (HR: 0.521, 95% CI: 0.33-0.82), underwent SRS therapy (HR: 0.531, 95% CI: 0.32-0.87), or were sequentially treated with osimertinib (HR: 0.400, 95% CI: 0.23-0.71) were associated with improved overall survival (OS). Furthermore, SRS plus EGFR-TKI provided more OS benefits in patients with Lung-mol GPA ≥3 compared with EGFR-TKI alone in our patient cohort (44.9 vs. 26.7 months, p = 0.005). The OS in patients who received sequential osimertinib therapy was significantly longer than those without osimertinib treatment (43.5 vs. 24.3 months, p < 0.001), regardless of T790 mutation status (positive vs. negative vs. unknown: 40.4 vs. 54.6 vs.43.4 months, p = 0.227). CONCLUSIONS: The study demonstrated that EGFR-mutant NSCLC patients with BMs could be precisely treated with SRS according to Lung-mol GPA ≥3. Sequential osimertinib was associated with prolonged survival, regardless of T790M status.

Significant Contribution of Interleukin-18 Genotypes to Lung Cancer Risk in Taiwanese.

BACKGROUND/AIM: The elevated expression of interleukin-18 (IL-18) among lung cancer patients raised our curiosity to examine the role of IL-18 genotypes in lung cancer. MATERIALS AND METHODS: IL-18 -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 358 lung cancer cases and 716 controls were determined via the PCR-RFLP methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 -607, but not those of -656 or -137, were differentially distributed between cases and controls. IL-18 -607 AC and CC genotypes were both lower (45.8% and 16.2%) in lung cancer patients compared to controls (51.4% and 24.7%). In addition, IL-18 -607 AC and CC genotypes were of significantly lower percentages both among non-smokers and smokers. Otherwise, no differential distribution was found regarding IL-18 -656 or -137. CONCLUSION: IL-18 -607 C allele can serve as a protective predictor for lung cancer risk in Taiwanese.

The Contribution of Interleukin-8 Rs4073 Genotypes to Triple Negative Breast Cancer Risk in Taiwan.

BACKGROUND/AIM: Triple negative breast cancer (TNBC) is one of the most challenging breast cancer types. Interleukin-8 (IL-8) is a pro-tumorigenic cytokine, promoting tumor proliferation and migration. This study aimed to examine the contribution of IL-8 rs4073 genotypes to breast cancer risk and provide a summary of related literature. MATERIALS AND METHODS: IL-8 genotypic profiles were determined among 1,232 breast cancer cases and 1,232 controls via polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The IL-8 rs4073 AT and AA genotypes had significantly lower prevalence in the case group compared to control group. Allelic frequency analysis showed that individuals carrying the A allele have relatively decreased risk for breast cancer. The stratification analysis showed that IL-8 rs4073 genotypes were protective markers for those with younger (≤55) age. CONCLUSION: IL-8 rs4073 A allele is a novel predictor for breast cancer, especially TNBC.

Advances in Diagnostic Bronchoscopy.

The increase in incidental discovery of pulmonary nodules has led to more urgent requirement of tissue diagnosis. The peripheral pulmonary nodules are especially challenging for clinicians. There are various modalities for diagnosis and tissue sampling of pulmonary lesions, but most of these modalities have their own limitations. This has led to the development of many advanced technical modalities, which have empowered pulmonologists to reach the periphery of the lung safely and effectively. These techniques include thin/ultrathin bronchoscopes, radial probe endobronchial ultrasound (RP-EBUS), and navigation bronchoscopy-including virtual navigation bronchoscopy (VNB) and electromagnetic navigation bronchoscopy (ENB). Recently, newer technologies-including robotic-assisted bronchoscopy (RAB), cone-beam CT (CBCT), and augmented fluoroscopy (AF)-have been introduced to aid in the navigation to peripheral pulmonary nodules. Technological advances will also enable more precise tissue sampling of smaller peripheral lung nodules for local ablative and other therapies of peripheral lung cancers in the future. However, we still need to overcome the CT-to-body divergence, among other limitations. In this review, our aim is to summarize the recent advances in diagnostic bronchoscopy technology.

Efficacy of adjunctive nebulized colistin in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial pneumonia: a multi-centre observational study.

OBJECTIVES: To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. METHODS: This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. RESULTS: In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37-0.92; model 2: aOR 0.37, 95% CI 0.21-0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2. CONCLUSIONS: Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.

Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection.

Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.