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The Pediatric Infectious Disease Journal Dec 2023To identify the difference in clinical characteristics between viral pneumonia and Mycoplasma pneumoniae , providing cues on their differential diagnosis for primary...
Differentiate Clinical Characteristics Between Viral Pneumonia and Mycoplasma pneumoniae and Nomograms for Predicting Mycoplasma pneumoniae : A Retrospective Study in Primary Hospitals.
OBJECTIVE
To identify the difference in clinical characteristics between viral pneumonia and Mycoplasma pneumoniae , providing cues on their differential diagnosis for primary hospitals with the insufficient pathogen detection capacity.
METHODS
We retrospectively reviewed the medical records of hospitalized children with acute respiratory tract infections, and pathogenic microbes test results were analyzed. Clinical characteristics, routine blood parameters and hospitalization duration and fee were compared between M. pneumoniae and viral pneumonia. We used in the multivariable logistic regression to predict the probability of children with M. pneumoniae and graphically represented by a dynamic nomogram. The discrimination and clinical utility of the model were confirmed by receiver operating characteristic and decision curve analysis curves.
RESULT
A total of 375 children with community-acquired pneumonia were included. Mycoplasma infection accounted for the largest proportion (22.13%). The incidence of both hypothermia and vomiting was lower in M. pneumoniae compared to viral pneumonia (hypothermia: 10.50% vs. 0.00%; vomiting: 7.90% vs. 0.00%). The prevalence of hyperthermia was higher in M. pneumoniae (hyperthermia: 89.5% vs. 100%). Procalcitonin, peripheral blood white blood cell count and lymphocyte levels were higher in the viral pneumonia group, and eosinophil levels were conversely lower. As for the duration of illness, the mean length of stay was 5.20 ± 2.12 (viral pneumonia) and 6.27 ± 2.48 days ( M. pneumoniae ). Children with M. pneumoniae had higher overall hospital costs and required more medical treatment. The above were all statistically significant with a P < 0.05. The scoring system was established based on the above results. Receiver operating characteristic curves showed good model-discrimination ability with 0.844 of the area under the curve in the training set and 0.778 in the test set. Decision curve analysis curves demonstrated the discriminative superiority of this model. The web-based dynamic nomogram calculator is accessible at https://zhxylxy0160128.shinyapps.io/Nomogram/ .
CONCLUSION
Nomograms have satisfactory discrimination, and clinical utility may benefit in predicting the probability of developing M. pneumoniae in children. Children with M. pneumoniae have a higher burden than those with viral pneumonia and may require more intensive in-hospital monitoring.
Topics: Child; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Retrospective Studies; Nomograms; Hypothermia; Pneumonia, Viral; Hospitals; Vomiting; Community-Acquired Infections
PubMed: 37820276
DOI: 10.1097/INF.0000000000004082 -
Journal of Clinical Microbiology Sep 2023Syndromic PCR-based analysis of lower respiratory tract (LRT) samples in patients with community-acquired pneumonia (CAP) improves the bacterial yield and... (Randomized Controlled Trial)
Randomized Controlled Trial Observational Study
Diagnostic utility of oropharyngeal swabs as an alternative to lower respiratory tract samples for PCR-based syndromic testing in patients with community-acquired pneumonia.
Syndromic PCR-based analysis of lower respiratory tract (LRT) samples in patients with community-acquired pneumonia (CAP) improves the bacterial yield and time-to-results compared to culture-based methods. However, obtaining adequate sputum samples can be challenging and is frequently not prioritized in the emergency department (ED). In this study, we assess the concordance of microbiological detections between oropharyngeal- (OP) and LRT samples from patients presenting to the ED with CAP using a syndromic PCR-based respiratory panel [Biofire FilmArray Pneumonia (FAP )]. Paired OP- and high-quality LRT samples were collected from 103 patients with confirmed CAP, who had been included in a randomized controlled trial (NCT04660084) or a subsequent observational study at Haukeland University Hospital, and analyzed using the FAP . The LRT samples were obtained mainly by sputum induction (88%). Using the LRT samples as a reference standard, the positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement for the most common bacterial pathogens in CAP, and , were 85%, 99% and 95%, and 86%, 98% and 93%, respectively. For the PPA was lower (74%), while the NPA was 100%. For bacteria that are less likely causes of uncomplicated CAP (e.g., and Enterobacterales) the results were more divergent. In conclusion, the FAP detects the most common CAP pathogens and from OP samples with high PPAs and excellent NPAs when compared with LRT samples. For these pathogens, the PPAs for OP samples were higher than previous reports for nasopharyngeal samples. This suggests that analysis of OP samples with syndromic PCR panels could represent an alternative approach for rapid microbiological testing in the ED, especially in patients where LRT samples are difficult to obtain. Divergent results for bacteria that are less likely to cause uncomplicated CAP do, however, emphasize the need for clinical evaluation of positive test results.
Topics: Humans; Pneumonia; Streptococcus pneumoniae; Polymerase Chain Reaction; Bacteria; Oropharynx; Community-Acquired Infections
PubMed: 37585220
DOI: 10.1128/jcm.00505-23 -
Chest Oct 2023Inhaled corticosteroids (ICS) increase the risk of pneumonia in COPD and commonly are used in patients with COPD-bronchiectasis overlap.
BACKGROUND
Inhaled corticosteroids (ICS) increase the risk of pneumonia in COPD and commonly are used in patients with COPD-bronchiectasis overlap.
RESEARCH QUESTION
Is the risk of pneumonia associated with ICS further heightened in COPD-bronchiectasis?
STUDY DESIGN AND METHODS
Electronic health care records (from 2004-2019) were used to obtain a cohort of patients with COPD and a nested case-control group (age and sex matched 1:4). Analyses were conducted to determine the risk of hospitalization for pneumonia in COPD associated with ICS use in those with bronchiectasis. Findings were confirmed by several sensitivity analyses. Additionally, a smaller nested case-control group containing only patients with COPD-bronchiectasis overlap and those with recent blood eosinophil counts (BECs) was used to determine any association with BEC.
RESULTS
Three hundred sixteen thousand six hundred sixty-three patients were eligible for the COPD cohort; bronchiectasis significantly increased the risk of pneumonia (adjusted hazard ratio, 1.24; 95% CI, 1.15-1.33). In the first nested case-control group of 84,316 patients with COPD, ICS was found to increase the odds of pneumonia (adjusted OR [AOR], 1.26; 95% CI, 1.19-1.32) only if used in the previous 180 days. However, bronchiectasis was a significant modifier such that ICS use did not augment further the already elevated bronchiectasis-associated pneumonia risk (COPD-bronchiectasis: AOR, 1.01; 95% CI, 0.8-1.28; no bronchiectasis: AOR, 1.27; 95% CI, 1.20-1.34). Several sensitivity analyses and a second smaller nested case-control group confirmed these findings. Finally, we found that BEC modified the ICS-associated pneumonia risk in COPD-bronchiectasis overlap, where lower BEC was associated significantly with pneumonia (BEC ≤ 3 × 10/L: AOR, 1.56; 95% CI, 1.05-2.31; BEC > 3 × 10/L: AOR, 0.89; 95% CI, 0.53-1.24).
INTERPRETATION
ICS use does not augment further the already increased risk of hospitalization for pneumonia associated with concomitant bronchiectasis in patients with COPD.
Topics: Humans; Administration, Inhalation; Bronchiectasis; Case-Control Studies; Pneumonia; Pulmonary Disease, Chronic Obstructive; United Kingdom; Glucocorticoids; Retrospective Studies; England
PubMed: 37419145
DOI: 10.1016/j.chest.2023.06.007 -
BMC Pediatrics Jul 2023To analyze the etiological distribution characteristics of pediatric patients with severe pneumonia admitted to the Pediatric Intensive Care Unit (PICU), in order to...
OBJECTIVE
To analyze the etiological distribution characteristics of pediatric patients with severe pneumonia admitted to the Pediatric Intensive Care Unit (PICU), in order to provide a reference for the rational use of clinical antimicrobial drugs.
METHODS
A retrospective analysis of pediatric patients admitted to PICU with a diagnosis of severe pneumonia from January 2018 to December 2021 was performed and statistical analysis of pathogenic characteristics was performed.
RESULTS
A total of 649 pathogens were detected in 515 children, with a positive detection rate of 77.48%. Bacteria were detected at the highest rate (40.52%), followed by viruses (34.35%), atypical pathogens (19.72%) and fungal (4.31%). Gram-positive infections were dominated by Staphylococcus aureus (39.56%) and Streptococcus pneumoniae (32.97%), and Gram-negative infections were dominated by Acinetobacter Bahmani (16.28%) and Haemophilus influenzae (15.12%), followed by Klebsiella pneumoniae (13.95%) and Pseudomonas aeruginosa (12.21%). Viral infections were dominated by respiratory syncytial virus (25.65%) and EB virus (20.43%), fungal infections were dominated by Candida albicans (50.0%). The proportion of children infected with single pathogen (49.62%) was comparable to that of those with mixed infections (50.38%). There were statistically significant differences in the distribution of children with single pathogen infection by gender (P < 0.05). The age distribution of children with single bacterial, single viral and single fungal infections was statistically different (P < 0.05). There was no significant difference in the distribution of onset season in children with single pathogen infections (P > 0.05), but the number of children with single viral infections was significantly higher in winter and spring than that in summer and autumn, and the difference was statistically significant (P < 0.05). A mixture of 2 pathogens (77.61%) accounted for the majority of mixed infections, there were statistical differences in the distribution of bacterial + viral infection in terms of gender, age, and onset season (P < 0.05), children with viral + mycoplasma infection in terms of gender and age (P < 0.05), and children with viral + fungal infection in terms of gender (P < 0.05), and children with bacterial + mycoplasma infection in terms of age and onset season (P < 0.05). Among the children infected with 3 pathogens, there were statistically significant differences in the distribution of bacterial + viral + fungal and viral + mycoplasma + fungal infections in terms of gender (P < 0.05), and children with bacterial + viral + mycoplasma infection in terms of age (P < 0.05), while there was no significant difference in the distribution of onset season (P > 0.05). There were no significant differences in the distribution of children infected with 4 pathogens in terms of gender, age and onset season (P > 0.05).
CONCLUSION
The pathogens of pediatric patients with severe pneumonia in PICU commonly involves bacteria and viruses. As the age of children grows, the detection rate of bacteria shows a decreasing trend, and the pathogenic spectrum gradually changes from bacteria to mycoplasma and viruses, and the number of mixed infections gradually increase. Rational selection of antimicrobial drugs needs to consider pathogenic characteristics of different age, gender, and onset season in clinical practice.
Topics: Child; Humans; Retrospective Studies; Coinfection; Pneumonia; Bacteria; Virus Diseases; Staphylococcal Infections; Intensive Care Units, Pediatric; Mycoplasma Infections
PubMed: 37454044
DOI: 10.1186/s12887-023-04175-y -
Oncogene Oct 2023Checkpoint inhibitor pneumonitis (CIP) is the most common fatal immune-related adverse event; however, its pathophysiology remains largely unknown. Comprehensively...
Checkpoint inhibitor pneumonitis (CIP) is the most common fatal immune-related adverse event; however, its pathophysiology remains largely unknown. Comprehensively dissecting the key cellular players and molecular pathways associated with CIP pathobiology is critical for precision diagnosis and develop novel therapy strategy of CIP. Herein, we performed a comprehensive single-cell transcriptome analysis to dissect the complexity of the immunological response in the bronchoalveolar lavage fluid (BALF) microenvironment. CIP was characterized by a dramatic accumulation of CXCL13+ T cells and hyperinflammatory CXCL9+ monocytes. T-cell receptor (TCR) analysis revealed that CXCL13+ T cells exhibited hyperexpanded- TCR clonotypes, and pseudotime analysis revealed a potential differentiation trajectory from naïve to cytotoxic effector status. Monocyte trajectories showed that LAMP3+ DCs derived from CXCL9+ monocytes possessed the potential to migrate from tumors to the BALF, whereas the differentiation trajectory to anti-inflammatory macrophages was blocked. Intercellular crosstalk analysis revealed the signaling pathways such as CXCL9/10/11-CXCR3, FASLG-FAS, and IFNGR1/2-IFNG were activated in CIP+ samples. We also proposed a novel immune signature with high diagnostic power to distinguish CIP+ from CIP- samples (AUC = 0.755). Our data highlighted key cellular players, signatures, and interactions involved in CIP pathogenesis.
Topics: Humans; Pneumonia; Neoplasms; Signal Transduction; Macrophages; Receptors, Antigen, T-Cell; Lung Neoplasms; Tumor Microenvironment
PubMed: 37653115
DOI: 10.1038/s41388-023-02805-4 -
Clinical Interventions in Aging 2023To investigate the predictive value of various inflammatory biomarkers in patients with acute ischemic stroke (AIS) and evaluate the relationship between...
PURPOSE
To investigate the predictive value of various inflammatory biomarkers in patients with acute ischemic stroke (AIS) and evaluate the relationship between stroke-associated pneumonia (SAP) and the best predictive index.
PATIENTS AND METHODS
We calculated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), prognostic nutritional index (PNI), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and prognostic index (PI). Variables were selectively included in the logistic regression analysis to explore the associations of NLR, PLR, MLR, PNI, SIRI, SII, GPS, mGPS, and PI with SAP. We assessed the predictive performance of biomarkers by analyzing receiver operating characteristic (ROC) curves. We further used restricted cubic splines (RCS) to investigate the association. Next, we conducted subgroup analyses to investigate whether specific populations were more susceptible to NLR.
RESULTS
NLR, PLR, MLR, SIRI, SII, GPS, mGPS, and PI increased significantly in SAP patients, and PNI was significantly decreased. After adjustment for potential confounders, the association of inflammatory biomarkers with SAP persisted. NLR showed the most favorable discriminative performance and was an independent risk factor predicting SAP. The RCS showed an increasing nonlinear trend of SAP risk with increasing NLR. The AUC of the combined indicator of NLR and C-reactive protein (CRP) was significantly higher than those of NLR and CRP alone (DeLong test, <0.001). Subgroup analyses suggested good generalizability of the predictive effect.
CONCLUSION
NLR, PLR, MLR, PNI, SIRI, SII, GPS, mGPS, and PI can predict the occurrence of SAP. Among the indices, the NLR was the best predictor of SAP occurrence. It can therefore be used for the early identification of SAP.
Topics: Humans; Ischemic Stroke; Stroke; Pneumonia; Biomarkers; Inflammation; C-Reactive Protein
PubMed: 37720840
DOI: 10.2147/CIA.S425393 -
Clinical Infectious Diseases : An... Mar 2024Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may... (Observational Study)
Observational Study
BACKGROUND
Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia.
METHODS
In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing.
RESULTS
Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%).
CONCLUSIONS
Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing.
CLINICAL TRIALS REGISTRATION
NCT04047719.
Topics: Adult; Humans; Prospective Studies; Pneumonia; Sequence Analysis, DNA; Immunocompromised Host
PubMed: 37815489
DOI: 10.1093/cid/ciad599 -
Annals of Medicine Dec 2023The assessment of severity is crucial in the management of community-acquired pneumonia (CAP). It remains unknown whether updating cut-off values of severity scoring...
The assessment of severity is crucial in the management of community-acquired pneumonia (CAP). It remains unknown whether updating cut-off values of severity scoring systems orchestrate improvement in predictive accuracy. 3,212 patients with CAP were recruited to two observational prospective cohort studies. Three bettered scoring systems were derived from the corresponding well-established and extensively used pneumonia-specific severity scoring systems, i.e. pneumonia severity index, minor criteria and CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30/min, low blood pressure, and age ≥65 years) score, with the updating cut-off values for tachypnea and low blood pressure. Cronbach α was employed to determine construct validity. Discrimination was valued by calculating the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI). Respiratory rate ≥22/min and systolic blood pressure ≤100 mm Hg were performed better than respiratory rate ≥30/min and hypotension for predicting mortality in the derivation cohort, respectively (AUROC, 0.823 vs 0.519, 0.688 vs 0.622; NRI, 0.61, 0.13). Bettered scoring systems orchestrated higher convergences, indicated by greater Cronbach α and more decrease in Cronbach α if the updating cut-off values were deleted. The six scoring systems agreed well with one another. Bettered- pneumonia severity index, minor criteria and CURB-65 score showed higher associations with severity and mortality rates and demonstrated greater predictive accuracies for mortality compared with the corresponding original systems (AUROC, 0.939 vs 0.883, 0.909 vs 0.871, 0.913 vs 0.859; NRI, 0.113, 0.076, 0.108; respectively). The validation cohort confirmed a similar pattern. Updating cut-off values of severity scoring systems for CAP orchestrate improvement in predictive accuracy, suggesting that it may facilitate the rationalization of clinical triage decision-making and further reduce mortality. The current studies provide the first known prospective evidence of potential benefit of the updating cut-off values of severity scoring systems for CAP in predictive accuracy.Key messagesUpdating cut-off values were performed better for predicting mortality.Bettered scoring systems orchestrated higher convergences.Bettered scoring systems demonstrated greater predictive accuracies for mortality.
Topics: Humans; Aged; Prospective Studies; Retrospective Studies; Pneumonia; Hypotension; ROC Curve; Community-Acquired Infections; Severity of Illness Index; Prognosis
PubMed: 37074414
DOI: 10.1080/07853890.2023.2202414 -
Journal of Critical Care Feb 2024Evaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP). (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Evaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP).
MATERIALS AND METHODS
Randomized, multicenter, double-blind, placebo-controlled, phase 1b/2a trial. Patients with severe CABP were enrolled to receive intravenous infusions of Cx611 or placebo. The primary objective was safety including hypersensitivity reactions, thromboembolic events, and immunological responses to Cx611. The secondary endpoints included the clinical cure rate, ventilation-free days, and overall survival (Day 90).
RESULTS
Eighty-three patients were randomized and received infusions (Cx611: n = 42]; placebo: n = 41]. The mean age was similar (Cx611: 61.1 [11.2] years; placebo: 63.4 [10.4] years). The number of AEs and treatment-emergent AEs were similar (243; 184 and 2; 1) in Cx611 and placebo respectively. Hypersensitivity reactions or thromboembolic events were similar (Cx611: n = 9; placebo: n = 12). Each study arm had similar anti-HLA antibody/DSA levels at Day 90. The clinical cure rate (Cx611: 86.7%; placebo: 93.8%), mean number of ventilator-free days (Cx611: 12.2 [10.29] days; placebo: 15.4 [10.75] days), and overall survival (Cx611: 71.5%; placebo: 77.0%) did not differ between study arms.
CONCLUSION
Cx611 was well tolerated in severe CABP. These data provide insights for future stem cell clinical study designs, endpoints and sample size calculation.
TRIAL REGISTRATION
NCT03158727 (retrospectively registered: May 09, 2017). Full study protocol: https://clinicaltrials.gov/ProvidedDocs/27/NCT03158727/Prot_000.pdf.
Topics: Humans; Community-Acquired Infections; COVID-19; Double-Blind Method; Pneumonia, Bacterial; SARS-CoV-2; Thromboembolism; Treatment Outcome; Middle Aged; Aged
PubMed: 37918129
DOI: 10.1016/j.jcrc.2023.154446 -
Frontiers in Immunology 2023The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Network Meta-Analysis; Neoplasms; Paclitaxel; Hypothyroidism; Pneumonia
PubMed: 37520574
DOI: 10.3389/fimmu.2023.1175809