Analyzing the characteristics of respiratory microbiota after the placement of an airway stent for malignant central airway obstruction.

Malignant central airway stenosis is treated with airway stent placement, but post-placement microbial characteristics remain unclear. We studied microbial features in 60 patients post-stent placement, focusing on changes during granulation tissue proliferation. Samples were collected before stent (N = 29), after stent on day 3 (N = 20), and after granulation tissue formation (AS-GTF, N = 43). Metagenomic sequencing showed significant respiratory tract microbiota changes with granulation tissue. The microbiota composition, dominated by Actinobacteria, Firmicutes, and Proteobacteria, was similar among the groups. At the species level, the AS-GTF group exhibited significant differences, with Peptostreptococcus stomatis and Achromobacter xylosoxidans enriched. Analysis based on tracheoesophageal fistula presence identified Tannerella forsythia and Stenotrophomonas maltophilia as the main differential species, enriched in the fistula subgroup. Viral and fungal detection showed Human gammaherpesvirus 4 and Candida albicans as the main species, respectively. These findings highlight microbiota changes after stent placement, potentially associated with granulation tissue proliferation, informing stent placement therapy and anti-infective treatment optimization. IMPORTANCE: Malignant central airway stenosis is a life-threatening condition that can be effectively treated with airway stent placement. However, despite its clinical importance, the microbial characteristics of the respiratory tract following stent insertion remain poorly understood. This study addresses this gap by investigating the microbial features in patients with malignant central airway stenosis after stent placement, with a specific focus on microbial changes during granulation tissue proliferation. The findings reveal significant alterations in the diversity and structure of the respiratory tract microbiota following the placement of malignant central airway stents. Notably, certain bacterial species, including Peptostreptococcus stomatis and Achromobacter xylosoxidans, exhibit distinct patterns in the after-stent granulation tissue formation group. Additionally, the presence of tracheoesophageal fistula further influences the microbial composition. These insights provide valuable references for optimizing stent placement therapy and enhancing clinical anti-infective strategies.

Bronchoscopic Intervention for Tracheobronchopathia Osteochondroplastica: A Report of Two Cases.

Tracheobronchopathia osteochondroplastica (TO) is an uncommon non-malignant tracheal ailment characterized by the existence of numerous bone and/or cartilage nodules in the submucosa of the trachea and bronchi. At present, there is a lack of standardized treatment recommendations for TO. This article presents two instances of severe tracheal stenosis caused by TO, which were effectively managed through the implementation of bronchoscopic stent placement and rigid bronchoscopy curettage, respectively. Both cases exhibited favorable outcomes, providing novel insights and references for the treatment of TO. Laryngoscope, 2024.

Central nervous system complications in SARS-CoV-2-infected patients.

OBJECTIVE: To investigate the clinical manifestations, treatment and prognosis of COVID-19-associated central nervous system (CNS) complications. METHODS: In this single-centre observation study, we recruited patients with COVID-19-associated CNS complications at the neurology inpatient department of the Eighth Affiliated Hospital, Sun Yat-Sen University (Futian, Shenzhen) from Dec 2022 to Feb 2023. Patients were analysed for demographics, clinical manifestations, cerebrospinal fluid properties, electroencephalographic features, neuroimaging characteristics, and treatment outcome. All patients were followed-up at 1 and 2 months after discharge until Apr 2023. RESULTS: Of the 12 patients with COVID-19-associated CNS complications, the CNS symptoms occur between 0 days and 4 weeks after SARS-CoV-2 infection. The most common CNS symptoms were memory deficits (4/12, 33%), Unresponsiveness (4/12, 33%), mental and behavioural disorders (4/12, 33%). Seven of 12 cases can be categorized as probable SARS-CoV-2 encephalitis, and 5 cases can be described as brainstem encephalitis, acute disseminated encephalomyelitis, optic neuritis, multiple sclerosis or tremor probably associated with SARS-CoV-2 infection. Six patients received antiviral therapy, and 11 patients received glucocorticoid therapy, of which 3 patients received human immunoglobulin synchronously. Nine patients recovered well, two patients had residual neurological dysfunction, and one patient passed away from complications associated with tumor. CONCLUSION: In this observational study, we found that the inflammatory or immune-related complications were relatively common manifestations of COVID-19-associated CNS complications, including different phenotypes of encephalitis and CNS inflammatory demyelinating diseases. Most patients recovered well, but a few patients had significant neurological dysfunctions remaining.

α-Synuclein Induces Neuroinflammation Injury through the IL6ST-AS/STAT3/HIF-1α Axis.

The aggregation of α-synuclein (α-syn) promotes neuroinflammation and neuronal apoptosis, which eventually contribute to the pathogenesis of Parkinson's disease (PD). Our microarray analysis and experimental data indicated a significant expression difference of the long noncoding RNA IL6ST-AS and its anti-sense strand, IL6ST, in α-synuclein-induced microglia, compared with unstimulated microglia. IL6ST is a key component of the IL6R/IL6ST complex in the microglial membrane, which recognizes extracellular inflammatory factors, such as IL6. Studies have shown that the binding of IL6 to the IL6R/IL6ST complex could activate the JAK2-STAT3 pathway and promote an excessive immune response in glia cells. Meanwhile, the phosphorylation and activation of STAT3 could increase the transcription of HIF1A, encoding a hypoxia-inducible factor related to cytotoxic damage. Our results indicated that the overexpression of IL6ST-AS induced by exogenous α-synuclein could inhibit the expression of IL6ST and the activation of JAK2-STAT3 pathway in HMC3 cells. In addition, a reduction in STAT3 resulted in the transcription inhibition of HIF1A and the acceleration of oxidative stress injury in SH-SY5Y cells co-cultured with α-synuclein-induced HMC3 cells. Our findings indicate that IL6ST-AS is an important factor that regulates microglia activation and neuronal necrosis in the progression of PD. In the HMC3 and SH-SY5Y cell co-culture system, the overexpression of IL6ST-AS led to microglial dysfunction and neurotoxicology through the IL6ST-AS/STAT3/HIF-1α axis. Our research revealed the relationships among α-synuclein, IL6ST, STAT3, and HIF-1α in the pathological process of PD and provided a new inflammation hypothesis for the pathogenesis of PD.

Transcriptome Sequencing Identifies Novel Immune Response Genes Highly Related to the Severity of Human Adenovirus Type 55 Infection.

Human adenovirus type 55 (HAdV-55) is considered a highly virulent pathogen causing severe and even deadly pneumonia in immunocompetent people. The mechanisms of HAdV-55-induced initiation and progression of severe pneumonia remain ambiguous. In the current study, we endeavored to identify novel immune response genes which are substantially involved in the pathogenesis of severe inflammation in HAdV-55-infected patients. HAdV-55-infected patients with upper respiratory tract symptoms (minor patients) and pneumonia (severe patients) were enrolled. Through transcriptome sequencing and quantitative real-time PCR, the peripheral blood mononuclear cells of the patients were analyzed. We found that the expression of eight genes, including Il18, Il36b, Il17rc, Tnfsf10, Tnfsf11, Tnfsf14, Tnfsf15, and Il1a, were closely correlated with the severity of HAdV-55 infection. Most of these genes belong to interleukin-1 family or tumor necrosis factor (TNF) superfamily, respectively. The changes in gene expression were confirmed by Western blot assay. Our data will be crucial for deepening the understanding of the pathogenic mechanisms of severe pneumonia in HAdV-55 infection.

[Interventional Bronchoscopies for the Treatment of 112 Cases with Complex Malignant Central Airway Diseases Involved in Bifurcation].

BACKGROUND: It is very difficult to deal with the comprehensive central airway diseases, especially the malignant airway obstruction. The aim of this study is to explore the clinical effects of multiple interventional bronchoscopies for the treatment of 112 cases with comprehensive malignant central airway diseases so as to evaluate the clinical applications of thermoablation and cryosurgery. METHODS: The 112 cases with malignant airway diseases retrospectively reviewed for bronchoscopic interventions performed in more than two lesions of carina and/or bifurcation. The age was from 22 to 90 years, which including 55 cases with squamous carcinoma (SQ), 16 adenocarcinoma (AD), 15 adenocystic carcinoma (ACC), 10 metastasis tumor (MT), 8 small cell lung carcinoma (SCLC) and 8 mixed carcinoma (MC). All bronchoscopic interventions such as argon plasma coagulation (APC), cryosurgery, electronic snare and stenting were performed under rigid bronchoscopy combined with electric bronchoscopy in general anesthesia. RESULTS: The 460 bronchoscopic procedures were successfully performed in 112 cases. Cryosurgery and APC were the most used in every group. Stent was more common in patients with MT, balloon dilation was more common in patients with ACC and AD. Electric snare and radioactive seeds implantation were frequently used in cases with SCLC. Trachea stricture is more severe in MT than that in others, while bronchus stricture is more severe than that of trachea in SQ and ACC group. Karnofsky performance score (KPS) is lower and shortness of breath score (SBS) is higher in MC, MT and SCLC group. Trachea and bronchus stricture is improved after comprehensive treatment in 5 groups except of mixed group. KPS increased and SS decreased significantly in 5 groups except of adenocarcinoma. In follow-up, the overall survival time (OS) is 15 months and median survival time is 10 months, especially OS is 28.4 months in ACC and 21.7 months in AD, 8.9 months in SCLC and 7.4 months in mixed group. CONCLUSIONS: APC combination with Cryosurgery and other bronchoscopic interventions are indicated for the treatment of complex or difficult airway diseases whether they are located in trachea or bronchus. It is a safe and rapid during procedure.

[Interventional Bronchoscopy for the Treatment of Pulmonary Sarcoma].

BACKGROUND: Pulmonary sarcoma is a rare malignant tumor in soft tissues. Resection is the preferred option to treat this tumor. The aim of this study is to explore the effect of interventional bronchoscopies in the treatment of pulmonary sarcoma if the patient is inoperable. METHODS: Sixteen cases with pulmonary sarcoma were retrospectively reviewed in our hospital from November 2008 to July 2014. The mean age was (53.1±5.4) years old. Rigid bronchoscopy was applied for the first procedure with general anesthesia, and electronic bronchoscopy was used for the second procedure or slight patients. RESULTS: Sixteen cases, which include 10 sarcomatoid carcinoma, 2 fibrosarcoma, 2 sarcoma, 1 fibromucoid sarcoma, and 1 spindle cell synovial sarcoma, were collected in this study. Eleven cases (68.8%) were peripheral and mainly located in the right upper lobe and left lower lobe. Five cases (31.2%) were central. Of these cases, 82% (9/11) were mixed and primary tumors in pulmonary tumor. Meanwhile, 56% (9/16) were intraluminal and 69% (11/16) were metastatic in central airway. All of the four cases with whole atelectasis were completely relieved through postbronchoscopic interventions. Three of the seven cases with segment atelectasis were completely reopened; two of them were partially relieved; and the remaining two had no response. The obstructive degree, Karnofsky performance status (KPS), and shortness of breathless score improved significantly after the treatment. CONCLUSIONS: Interventional bronchoscopy could rapidly and efficiently remove endobronchial tumor, relieve airway obstruction, and improve clinical symptoms.

Airway Covered Metallic Stent Based on Different Fistula Location and Size in Malignant Tracheoesophageal Fistula.

BACKGROUND: Malignant tracheoesophageal fistula (MTEF) is a devastating complication of esophageal cancer, lung cancer or other carcinoma with a shorter life-span and poor life quality. The aim of this study was to assess the effect of airway stent insertion on MTEF patients. METHODS: A total of 63 MTEF patients were included, 12 patients with lung cancer and 46 patients with esophageal cancers. Eight zones were proposed to classify various fistula locations. Airway stents were selected based on the various zones and fistula size. RESULTS: Airway stents were successfully inserted in all patients, and both airway and esophageal stents in 8 patients. Most fistula were located in locations II (18/63, 28.6%), III (22/63, 34.9%), then VII (9/63, 14.3%). The stents included 10 (15.9%) I shaped, 8 (12.7%) L shaped and 45 (71.4%) Y shaped. Different stents were placed based on different locations and sizes of fistulas. Overall, mean survival time was 163 days (2-270 days). Most symptoms relieved after stent insertion. Mean Karnofsky score jumped from 43.0 ± 10.7 before stent placement to 66.7 ± 10.8 after stent insertion (P = 0.000). Complete closure was achieved in 45 patients (71.4%), and incomplete closure and leakage were found in 18 patients. CONCLUSIONS: Airway stent insertion provides an effective approach to improve symptoms and quality of life. The choice of stent based on different fistula location and size may be a reasonable way in clinical practice.

Effect of Acute Hypercapnia on Outcomes and Predictive Risk Factors for Complications among Patients Receiving Bronchoscopic Interventions under General Anesthesia.

BACKGROUND: The aim of this study is to investigate the effect of acute hypercapnia on surgery outcomes among patients receiving bronchoscopic interventions under general anesthesia. Furthermore, independent predictive factors for surgery complications were analyzed. METHOD: A total of 323 patients with airway stenosis were enrolled in this retrospective study. Each patient underwent interventional rigid bronchoscopy under general anesthesia. Arterial blood gas (ABG) was measured intraoperatively. In light of PaCO2 levels in ABG, patients were divided into three groups: Group C (control) (PaCO2:≤ 60 mmHg), Group M (moderate) (PaCO2:61-100 mmHg), and Group S (severe) (PaCO2: >100 mmHg). Parameters, including PaO2 levels and recovery delays, were compared across three groups. Complications among patients receiving bronchoscopic interventions were evaluated as well. Independent predictive factors for surgery related complications were analyzed by multivariable regression method. RESULTS: Significant differences in weight (p=0.04), ASA IV (p=0.008), dyspnea index (p=0.003),COPD (p=0.02), dynamic airway collapse (p=0.002), severe stenosis severity (p=0.02), and stenosis locations among three groups were observed. Mild (PaCO2:~60 mmHg) to moderate (PaCO2:60-100 mmHg) hypercapnia was not associated with delayed recovery, whereas severe hypercapnia (PaCO2:>100 mmHg) was associated with delayed recovery, as well as declined PaO2 (p=0.00) and elevated blood glucose levels (p=0.00). The complications of bronchoscopic interventions included postoperative congestive heart failure (14 cases, 4.3%), tracheorrhagia (8 cases, 2.5%), delayed recovery (19 cases, 5.9%), and transfers to ICU after surgery (10 cases, 3.1%). The multivariable regression analysis showed that procedure duration (p=0.003), lobectomy (p=0.007), dynamic airway collapse (p=0.01), severe bronchial stenosis (p=0.01) and hypercapnia (p=0.02) were independent predictive factors for surgery related complications. CONCLUSIONS: Acute hypercapnia lower than 100 mmHg was not associated with detrimental consequences, whereas severe hypercapnia (PaCO2: >100 mmHg) was associated with lower levels of PaO2. Hypercapnia was an independent predictive factor for bronchoscopic intervention complication, which may help physicians to optimize the therapeutic choices.

Efficacy of bronchoscopic therapies for bronchial mucoepidermoid carcinoma in children: results from six patients.

AIMS AND BACKGROUND: Bronchial mucoepidermoid carcinoma is a rare disease in children, and lobectomy is traditionally considered as a first-line treatment. As the tumor is characterized by intraluminal growth, low malignancy and superficial infiltration of bronchial walls, bronchoscopic interventional therapy may provide an alternative treatment with favorable results. The aim of the study was to evaluate the efficacy and safety of bronchoscopic therapies for bronchial mucoepidermoid carcinoma in children. METHODS AND STUDY DESIGN: Clinical manifestations, multiple bronchoscopic interventions and outcomes in 6 children with bronchial mucoepidermoid carcinoma were retrospectively analyzed. RESULTS: The median age was 8.7 years (range 4 to 12 years). All the tumors were located in the lobar bronchus and were detected by computerized tomography. Diagnoses of low-grade mucoepidermoid carcinoma were made based on biopsies obtained via bronchoscopy. Five tumors were classified as intraluminal type and successfully eradicated by carbon dioxide cryotherapy and argon plasma coagulation under bronchoscopy. The other tumor in patient 3 was classified as the mixture type and could not be removed by a bronchoscopic, so left upper lobectomy was performed. For each patient, interventional procedures were conducted on the average for 6 times. No recurrence was detected by bronchoscopic inspections or computed tomography scans during follow-ups for 16-72 months. CONCLUSIONS: Multiple bronchoscopic procedures, as alternative treatments, are effective in removing bronchial mucoepidermoid carcinoma mucoepidermoid carcinoma in children without any major complications.

Bronchoscopic intervention as a main treatment for tracheobronchial adenoid cystic carcinoma.

BACKGROUND: Bronchial adenoid cystic carcinoma (ACC) is a rare disease with low malignancy and indolent progression. Airway obstruction caused by ACC can be resolved by endoscopic procedures. The efficacy of different techniques of bronchoscopic interventions for ACC has not been determined. MATERIAL AND METHODS: From November 2004 to March 2012, ACC patients, mainly treated with different techniques of bronchoscopic interventions in our hospital, were reviewed. RESULTS: The study included 37 ACC patients. Five patients (13.5%) with intra-luminal type underwent bronchoscopic therapies for a median of three times (range 1-6 times). Thirty-two patients (86.5%) with mixed type underwent bronchoscopic interventions for a median of 14 times (range 4-20 times). The dyspnea index was significantly improved after the first endoscopic procedure. The overall five- and ten-year survival rate was 85.9% and 45.9%, respectively, similar to surgery-dominant treatments. CONCLUSIONS: The present study demonstrates that different procedures of bronchoscopic interventions, as main treatments for ACC, are as effective as surgery-dominant treatment. More prospective and multicentric studies are required to confirm these favorable results, which may influence the therapeutic strategy for ACC in the future.

[Electrocautery snare is combined with CO2 cryosurgery and argon plasma coagulation for the treatment of airway tumors and granulomas].

BACKGROUND: To observe the clinical effects and safety of endobronchial electrocautery snare combined with CO2 cryosurgery for the treatment of tracheobronchial obstructive lesions. METHODS: Seventy-seven patients with airway tumor or granuloma were retrospectively reviewed, including 70 malignant airway obstruction and 7 benign airway lesions, for the treatment of endobronchial electrocautery snare plus CO2 cryosurgery and argon plasma coagulation (APC). RESULTS: Eighty-five endobronchial snares were performed in 77 cases. 42.9% of the obstructive lesions were located in right bronchial orifice, 38.3% in main trachea 21.4% in left bronchial orifice. 89.7% of the malignant tumor was mixed type of lesions (endobronchial plus bronchial or external bronchial), only 10.3% was endobronchial. Obstructive stenosis was significant relieved after snare (80% before vs 20% after, P<0.01) in all patients. Karnofsky Performance Status (KPS) and shortbreath score were obviously improved after snare. There was no severe complications related to the procedures. CONCLUSIONS: Endobronchial electrocautery snare is an effective and safe approach for tracheobronchial obstructions with few complications.

[Radioactive seed implantation for the treatment of mediastinal malignant tumors and lymph node metastases in 43 cases].

BACKGROUND AND OBJECTIVE: The locations of mediastinal malignant tumor lesions are deep and occult, and are close to the pericardium, trachea, or major vessels. Therefore, the possibility of surgical resection is slim, and cryoablation and thermal ablation are restricted. In current study, image and life quality data were compared before and after 125I seeding therapy to investigate its safety and clinical effects. METHODS: From July 2010 to July 2011, a 43-patient follow-up of pathologically confirmed cancers, including 21 cases of primary mediastinal squamous lung cancer, 9 cases of primary esophagus cancer, and 13 cases of lymph node metastases were completed. Among these, 18 cases presented with tracheal stenosis >50%, 9 cases had esophageal obstruction, and 9 cases had superior vena cava reflux disorder. Each lesion was implanted with 10 to 60 pieces of 125I particles, with an average of 30.79±14.23. CT data at 2, 4, 6, and 12 months after therapy were obtained to evaluate the local lesion outcome. The quality of life of the patients as well as survival data was also recorded. RESULTS: The overall success rate of the operation was 100%. The longest time of follow-up was 12 months. At 6 months, 37 patients were alive, and the half-year survival rate was 85.0%. In terms of local lesions, 30 cases of PR and 7 cases of NC were found. The clinical effective rate was 81.08%, and the clinical beneficial rate was 100%. At 12 months after therapy, 31 patients were alive, and the one-year survival rate was 60.5%. In terms of local lesions, 16 cases of CR, 7 cases of PR, 2 cases of NC, and 6 cases of PD were found. The clinical effective rate was 74.19%, and the clinical beneficial rate was 80.65%. The KPS score increased after the treatment (P=0.000). Three cases of pneumothorax presented after treatment, and no severe complications, such as vessel, trachea, recurrent laryngeal nerve, or pericardiocentesis injuries, were found. CONCLUSIONS: Radiation seed implantation in mediastinal malignant tumors is a relatively safe technique with high success rate, considerable efficacy, and clear clinical value in advanced cancer treatment.

[Infection of human papillomavirus 16/18 DNA in patients with head and neck squamous cell carcinoma and its relationship with expression of Ki-67 and P53 protein].

OBJECTIVE: To detect the infection of human papillomavirus (HPV) 16/18 in patients with head and neck squamous cell carcinoma and explore the relationship between HPV infection and expressions of Ki-67 and P53 proteins in tumor tissue. METHOD: The level of HPV 16/18 DNA was measured by real time polymerase chain reaction, and Ki-67 and P53 proteins were measured by immunohistochemistry in tissues from head and neck squamous cell carcinoma. RESULTS: HPV 16/18 DNA was detected in 62.8% of our patients. In each cancer tissue sample, Ki-67 protein was expressed between 2% to 70%. P53 protein was expressed in 46.15% of our patients. No significant relation was found between HPV 16/18 DNA level and sex, smoking, drinking, and tumor clinical stages. However, level of HPV 16/18 DNA was found to have positive relation with tumor pathological grades and negative relation with P53 protein expression. No relation with Ki-67 protein expression was found. CONCLUSION: Head and neck squamous cell carcinoma may be initiated by HPV 16/18 infection and the mechanism in carcinogenesis involves abnormal expression in P53 protein.