A poised chromatin platform for TGF-ß access to master regulators.

Specific chromatin marks keep master regulators of differentiation silent yet poised for activation by extracellular signals. We report that nodal TGF-ß signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. The PHD-Bromo cassette of TRIM33 facilitates binding of TRIM33-Smad2/3 to H3K9me3 and H3K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. The crystal structure of this cassette, bound to histone H3 peptides, illustrates that PHD recognizes K9me3, and Bromo binds an adjacent K18ac. The interaction between TRIM33-Smad2/3 and H3K9me3 displaces the chromatin-compacting factor HP1γ, making nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal effectors use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state.

Nomogram Prediction Model of the Severity of CAP Patients Based on Blood Indicators.

BACKGROUND: Community-acquired pneumonia (CAP) is a common cause of hospitalization, characterized by high mortality, morbidity, and cost and has serious human health implications. Various scoring criteria have been used to predict the severity of pneumonia, including the CURB-65 score, Pneumonia Severity Index (PSI) score, and Severe Community-Acquired Pneumonia (SCAP) score. However, these scoring criteria have shortcomings such as low sensitivity, cumbersome clinical application, and limited application. This study aimed to construct a nomogram model to predict the severity of CAP patients by blood indicators. METHODS: This is a retrospective study. Patients with CAP were enrolled and then tested by routine blood, coagulation series, biochemical and inflammatory indicators, and general information such as imaging findings and disease history of the patients were recorded. The main observation was the progression of the patients' disease. Univariate analysis and binary logistic regression analysis were used to explore the independent risk factors for the severity of CAP patients, followed by plotting a nomogram to obtain the prediction model and constructing calibration curves to assess the authenticity and accuracy of the prediction model. Finally, the sensitivity, specificity, and other evaluation indexes were calculated by the receiver operating characteristic curve (ROC) to evaluate the clinical application value of the nomogram prediction model. RESULTS: Univariate analysis and binary logistic regression analysis of 277 hospitalized patients yielded platelet to lymphocyte ratio (PLR) and serum amyloid A (SAA) as independent risk factors for the severity of CAP patients. The AUC of the nomogram model for PLR and SAA was 0.889 (95% CI 0.845 - 0.932). The sensitivity was 77.3%, and the specificity was 85.3%, which had an excellent predictive value. CONCLUSIONS: The nomogram model based on PLR and SAA to predict the severity of CAP patients has a high specificity and sensitivity.

T-SPOT.TB Negative and Diagnosed as Interstitial Pulmonary Tuberculosis by NGS: a Case Report and Literature Review.

BACKGROUND: Tuberculosis is an airborne infectious disease with multiple morphologic changes on chest imaging. Tuberculosis-specific enzyme-linked immunospot assay (T-SPOT.TB) is widely used in the diagnosis of tuberculosis. Clinically, pulmonary tuberculosis with T-SPOT.TB negative and interstitial changes is very rare. METHODS: T-SPOT.TB, pathogenetic testing, chest CT scan, next-generation sequencing (NGS). RESULTS: Laboratory tests showed negative T-SPOT.TB and sputum antacid staining, chest CT showed interstitial fibrosis and multiple high-density shadows in both lungs, and sputum NGS showed Mycobacterium tuberculosis infection. CONCLUSIONS: Negative T-SPOT.TB and interstitial lung changes do not exclude Mycobacterium tuberculosis infection. NGS has a high specificity in the detection of pathogens in infectious diseases, especially in complex, mixed infectious diseases.

Positive PPD Test and TB-Ab Misdiagnosed as Tuberculosis Finally Proved as Sarcoidosis by Thoracoscopy: a Case Report.

BACKGROUND: Tuberculosis (TB) is a common infectious disease in developing countries. Tuberculosis and sarcoidosis are difficult to differentiate. We report a case of a patient who was initially misdiagnosed as tuberculosis due to positive tuberculin test (PPD test) and tuberculosis antibody (TB-Ab), which was eventually proven as sarcoidosis by thoracoscopy. METHODS: Appropriate laboratory tests are carried out and a chest CT scan, bronchoscopy, thoracoscopic pathological biopsy were done. RESULTS: Serum sedimentation was increased and tuberculosis antibody was positive. The chest CT scan showed multiple pulmonary nodules in both lungs. The bronchoscopy demonstrated no abnormality. Thoracoscopic pathology showed noncaseating granulomas and acid-fast staining was negative. CONCLUSIONS: When a patient has multiple pulmonary nodules and lymphadenopathy without obvious tuberculosis poisoning symptoms, physicians should pay attention to tuberculosis, sarcoidosis, and lung cancer. Pathology is crucial for the ultimate diagnosis.

Non-Tuberculous Mycobacteria with Enlarged Mediastinal Lymph Node by Next Generation Sequencing: Case Report.

BACKGROUND: A young patient characterized by rapid enlargement of mediastinal lymph nodes was diagnosed as non-tuberculous mycobacterial pulmonary disease (NTM-PD) by bronchoalveolar lavage fluid Next Generation Sequencing (NGS). METHODS: Laboratory examination, Chest CT scan, electronic bronchoscopy, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were performed to diagnose non-tuberculous mycobacterium pulmonary disease. RESULTS: Detection of bird-intracellular mycobacterium complex in bronchoalveolar lavage fluid by NGS. Chest CT scan showed multiple enlarged lymph nodes in mediastinum. 4R region TBNA: chronic granulomatous inflammation, positive bacilli were found by acid-fast staining. After the anti-NTM treatment, the symptoms of the patients were relieved. CONCLUSIONS: When the patient shows mediastinal lymph node enlargement of unknown cause, NTM-PD can be considered and NGS can be used to assist in the diagnosis.

Procalcitonin (PCT) Improves the Accuracy and Sensitivity of CURB-65 Score in Predicting CAP Patients Admission to ICU.

BACKGROUND: The CURB-65 scoring system is a simple tool for assessment and prognosis prediction for community-acquired pneumonia (CAP) patients. However, the variations in the performance of CURB-65 in young and elderly patients, underestimation, or overestimation of the severity have often been reported. It is worth noting that the application of biomarkers is helpful for improving the accuracy of the scoring system. In recent years, more and more reports and studies paid attention to procalcitonin (PCT) in respiratory infectious diseases, and its clinical value has attracted increasing attention. The study aimed at investigating the effectiveness of the CURB-65 score combined with PCT in predicting admission of CAP patients to intensive care units (ICU). METHODS: We conducted a retrospective study. We analyzed data from 520 non-immune individuals over the age of 18 in this study. All patients received blood indicators measurement and CURB-65 score calculation on admission. The primary outcome used to assess the probability of a CAP patient was who would get a bed in general ward or ICU. Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of the CURB-65 model and PCT combined CURB-65 augmented model in predicting the main outcomes. RESULTS: After analyzing the data from 520 patients, we found that the probability of entering the ICU was 22.1% (115/520). The AUC of Combination 1 (PCT&CURB-65 scores), Combination 2 (WBC&CURB-65 scores), Combination 3 (hs-CRP&CURB-65 scores) and Combination 4 (D-dimer&CURB-65 scores) for predicting CAP patients entering the ICU was 0.92 (95% CI 0.88 - 0.95), 0.91 (95% CI 0.87 - 0.94), 0.89 (95% CI 0.85 - 0.92), and 0.90 (95% CI 0.87 - 0.94), respectively, with statistically significant differences (p = 0.00); the sensitivities were 0.83, 0.82, 0.77 and 0.77, respectively, and the specificities were 0.92, 0.84, 0.90 and 0.91, respectively. PCT was superior to other indexes to improve the sensitivity and specificity of the CURB-65 score. CONCLUSIONS: Procalcitonin improves the accuracy and sensitivity of the CURB-65 score in predicting the probability of CAP patients entering the ICU, and PCT was superior to other indexes to improve the sensitivity and specificity of the CURB-65 score.

Organizing Pneumonia with NGS False-Positive Imaging Resembling Tuberculosis: a Case Report.

BACKGROUND: Organizing pneumonia (OP) is a pathologic concept characterized by the formation of granulation tissue from fibroblasts, myofibroblasts, collagen, and fibrotic exudate in the respiratory fine bronchi, alveolar ducts, and alveoli. The clinical imaging of mechanized pneumonia is variable, and histopathological examination is required to clarify the nature of the lesion when imaging is atypical. We report a case of OP with imaging resem-blance to pulmonary tuberculosis and false-positive next-generation sequencing (NGS), which was first misdiag-nosed as pulmonary tuberculosis. METHODS: Appropriate laboratory tests, alveolar lavage fluid NGS, chest CT, bronchoscopy, percutaneous lung puncture, pathology. RESULTS: Chest CT showed a nodular high-density shadow in the lower lobe of the right lung. According to the chest CT, bronchoalveolar lavage was performed in the dorsal segment of the right lower lobe of the lung. NGS of lavage fluid: the sequence number of Moraxella osseae was 1,423; the sequence number of Prevotella melanogaster was 1,129. Based on lung histopathology, fibrous emboli and necrotic material were seen in the alveolar lumen, and the final diagnosis of the OP was confirmed. CONCLUSIONS: It should be noted that physicians should not blindly believe the NGS result report. When the diagnosis is not clear and anti-infection treatment is ineffective, lung tissue should be obtained promptly for pathological examination to obtain pathological evidence to differentiate from misdiagnosed diseases.

Mycobacterium Tuberculosis Infection in AECOPD Combined with Pulmonary Embolism: a Case Report.

BACKGROUND: Mycobacterium tuberculosis belongs to the group of mycobacteria, most of which can cause a delayed hypersensitivity reaction in the body and is a bacterium that causes tuberculosis. Mycobacterium tuberculosis infection often presents with symptoms of tuberculosis toxicity and rarely with respiratory distress. At the same time, chest imaging often shows an ill-defined solid shadow in the apical and posterior segments of the upper lobe and, less frequently, in the dorsal segment of the lower lobe, and less frequently a diffuse nodular shadow. We report a case of AECOPD combined with pulmonary embolism infected with Mycobacterium tuberculosis. METHODS: Bronchoscopy, Next-generation sequencing (NGS). RESULTS: Antacid staining of bronchoalveolar lavage fluid suggested that a small amount of Mycobacterium antacid was visible. NGS was sent for examination and it suggested the presence of Mycobacterium tuberculosis with a sequence number of 5 (reference range ≥ 0). Treatment such as bronchodilation and antituberculosis was given. CONCLUSIONS: In patients with dyspnea, it is crucial to find the causative agent and to promptly improve relevant examinations such as pulmonary arteriography and bronchoscopy, and if necessary, to make a definitive diagnosis by NGS.

Rare Co-Infection of the Lungs with EBV and Pneumocystis Carinii in a Patient with Kidney Cancer: a Case Report.

BACKGROUND: Epstein-Barr virus (EBV) is the primary agent of infectious mononucleosis, lymphoma, and naso-pharyngeal carcinoma, but rarely involves the lungs. Pneumocystis carinii is commonly found in patients with HIV infection and is not pathogenic when the host is healthy, but opportunistic infections can occur when the body is immunocompromised, causing pneumocystis pneumonia (PCP). It is rare for both diseases to occur in the lungs of the same patient. METHODS: Next-generation sequencing (NGS), laboratory examination, chest CT scan, electronic bronchoscopy, and pathogenetic examination were used in this study. RESULTS: Laboratory tests showed (1-3)-ß-D-glucan of 889.47 pg/mL, negative human immunodeficiency virus (HIV) antibody, and negative Aspergillus immunological test. Chest CT showed multiple high-density shadows in both lungs, and EBV infection combined with Pneumocystis carinii pneumonia was confirmed by bronchoscopic biopsy and NGS examination. CONCLUSIONS: Elevated serum (1-3)-ß-D-glucan is not a specific index for infectious diseases. Bronchoscopy and the NGS has high specificity in pathogen detection of infectious diseases.

D-Dimer and Procalcitonin Improve the Sensitivity of BAP-65 Score in Predicting AECOPD Patients Admission to ICU.

BACKGROUND: The study aimed at investigating the effectiveness of the BAP-65 score combined with D-dimer and procalcitonin (PCT) in predicting admission of acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients to the intensive care unit (ICU). METHODS: We conducted a retrospective study. We analyzed data from 369 patients over the age of 40 years ad-mitted to our hospital with AECOPD. All patients received blood routine measurements and BAP-65 score calculation on admission. Receiver operating characteristic curves (ROC) were used to assess the sensitivity and specificity of D-dimer, PCT, and BAP-65 scores and combined metrics in predicting the risk of admissions to the ICU of AECOPD patients. RESULTS: We found that the percentage of patients with AECOPD admitted to the ICU was 32.25% (119/369). The area under the curve (AUC) of D-dimer, PCT, and BAP-65 score in individually predicting the probability of entering the ICU of AECOPD patients were 0.74 (95% CI 0.68 - 0.80), 0.83 (95% CI 0.78 - 0.88), and 0.72 (95% CI 0.66 - 0.79), respectively. The sensitivities of D-dimer, PCT, and BAP-65 score were 0.51, 0.65, and 0.52, respectively. The specificities of D-dimer, PCT, and BAP-65 score were 0.90, 0.91, and 0.92, respectively. The AUC of D-dimer and PCT combined with BAP-65 score was 0.90 (95% CI 0.86 - 0.94), the sensitivity and specificity were 0.90 and 0.80, respectively. CONCLUSIONS: D-dimer and procalcitonin improve the sensitivity of the BAP-65 score in predicting the probability of AECOPD patients entering the ICU while having a good specificity.

Organizing Pneumonia Secondary to Infection with Coxiella Burnetii: a Case Report.

BACKGROUND: Organizing pneumonia is a non-specific inflammatory response to various types of damage to the lungs. It is usually considered bacterial pneumonia that has not been absorbed for more than 4 weeks, accompanied by granulomas and fibrosis. Lung lesions in patients with organizing pneumonia are usually irreversible and the prognosis is relatively poor. Coxiella burnetii can cause Q fever. Acute Q fever usually presents as a self-limiting febrile illness with a good prognosis, but there are few cases of coexisting organizing pneumonia. We report a case of organizing pneumonia secondary to Coxiella burnetii infection. METHODS: Percutaneous lung biopsy, Next-generation sequencing (NGS). RESULTS: Percutaneous lung biopsy showed the existence of organizing pneumonia, and external examination of NGS showed the existence of Coxiella burnetii infection. After symptomatic treatment with azithromycin and glucocorticoids, the patient improved and was discharged from the hospital. CONCLUSIONS: For lesions with obvious heterogeneous enhancement on chest CT imaging, percutaneous lung biopsy or bronchoscopy should be performed promptly to obtain pathological tissue, and NGS should be used for definite diagnosis if necessary.

A Predictive Model Based on Blood Indicators for Admission to the ICU with AECOPD.

BACKGROUND: AECOPD is the most common cause of death among infectious diseases in developing countries, and also an important cause of mortality and morbidity in developed countries. In recent years, related scoring systems such as the mMRC score and CAT questionnaire have been widely used to assess the severity of AECOPD. However, they both have some shortcomings in predicting the admission of AECOPD patients to the ICU. This study aimed to develop a new prediction model to predict the admission of AECOPD patients to the ICU based on objective blood indicators. METHODS: This was a retrospective study. Enrolled patients with AECOPD underwent blood gas analysis as well as biomarker testing for serum inflammatory markers, including white blood cell count (WBC), neutrophils, D-dimer, procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR). General characteristics such as age and gender were also recorded. The main observation was admission to the ICU. Univariate analysis and binary logistic regression analysis were used to explore independent risk factors for admission to the ICU in patients with AECOPD, which could be used as components of a new predictive model. Subject receiver operating characteristic curves (ROC) were used to assess the sensitivity and specificity of the new model, which consisted of all independent risk factors predicting the primary outcome. RESULTS: Initially, 369 patients with AECOPD were admitted to the general ward, of which 119 were subsequently transferred to the ICU (119/369). PaCO2, WBC, D-dimer, PCT, and hs-CRP were independent risk factors for admission to the ICU in patients with AECOPD. The AUC of the new prediction model (combined model consisting of PaCO2, WBC, D-dimer, PCT, and hs-CRP) was 0.94 (95% CI 0.92 - 0.97). The sensitivity was 80.7% and the specificity was 94.8%. CONCLUSIONS: The model for predicting the admission of AECOPD patients to the ICU based on blood indicators has a high specificity and sensitivity.

Initial Elevated Myocardial Enzymes were Neglected in Lung Adenocarcinoma ICIS Associated Myocarditis: a Case Report.

BACKGROUND: In recent years, immunotherapy has gradually become the first or second-line drug for non-small cell lung cancer. However, the side effects associated with immunotherapy should not be underestimated. Toxic reactions are commonly seen in the skin, endocrine, and liver, and rarely in the heart and nerves. These effects are often life-threatening when they occur. In this paper, we present a case of ICIs-associated myocarditis in advanced lung adenocarcinoma with unappreciated initial cardiac enzyme elevation in a driver gene negative. METHODS: After electronic bronchoscopy and pathological examination, the patient was diagnosed with driver gene-negative advanced lung adenocarcinoma and treated with ICIs. RESULTS: Driver gene-negative advanced lung adenocarcinoma, effectively treated with ICIs, initially had elevated cardiac enzymes and unilateral ptosis, but was not taken seriously and the patient eventually died after discharge from the hospital. CONCLUSIONS: For patients with driver gene-negative advanced lung adenocarcinoma treated with ICIs, regular and periodic monitoring of myocardial damage markers is a top priority, followed by timely initiation of hormonal therapy as a means to improve prognosis.

A New Prediction Model for Prolonged Hospitalization in Adult Community-Acquired Pneumonia (CAP) Patients.

BACKGROUND: As a serious and common out-of-hospital infectious disease, community-acquired pneumonia (CAP) ranks among the leading causes of death in both developing and developed countries. In recent years, the increasing incidence of CAP has led to an increase in the number of hospitalizations. Although CURB-65 (or CRB-65) and pneumonia severity Index (PSI) scoring systems are widely used in CAP prognostic scoring systems, each score had some limitations in predicting whether patients with CAP would require prolonged hospitalization. The aim of this study was to analyze serum inflammatory biomarkers combined with age to establish a novel predictive model for predicting prolonged hospitalization in patients with CAP. METHODS: In a retrospective study, serum inflammatory biomarkers were collected from all enrolled CAP patients, including white blood cell count (WBC), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), D-dimer, procalcitonin (PCT), fibrinogen (FIB), and ICU treatment. Length of hospital stay and age were also recorded. The 75th percentile of length of stay in the enrolled population was defined as long hospitalization over time, and the primary predictor of outcome was prolonged hospitalization. Univariate analysis and binary logistic regression analysis were used to explore the independent risk factors which could be components of a new predicting model for prolonged hospitalization in CAP patients. ROC curves were used to evaluate the sensitivity and specificity of the new model, which consisted of the combination of all independent risk factors in predicting the main outcomes. RESULTS: The results showed that among 364 patients with CAP, 85 had extended hospitalization (85/364). Further analysis showed that age, white blood cell, fibrinogen, and high-sensitivity C-reactive protein were independent risk factors for extended hospitalization in patients with CAP. Finally, the AUC of the ROC curve of the new prediction model (the joint model consists of age, WBC, FIB, and hs-CRP) was 0.93 (95% CI 0.90 - 0.96), and the sensitivity and specificity were 87.1% and 87.8%, respectively. CONCLUSIONS: Serum inflammatory biomarkers combined age have high specificity and sensitivity in predicting prolonged hospitalization in adult CAP patients.

Carcinoembryonic Antigen Elevation in Broncholithiasis Patients Initially Misdiagnosed as Lung Cancer: a Case Report.

BACKGROUND: We report a case of broncholithiasis with recurrent pulmonary infection accompanied by blood in the sputum, which was initially misdiagnosed as lung cancer after laboratory examination indicating elevated carcinoembryonic antigen. METHODS: Laboratory examination, enhanced chest CT scan, electronic bronchoscopy, and ultra-thin bronchoscopy were performed to diagnose broncholithiasis. RESULTS: Carcinoembryonic antigen levels were elevated. Chest CT scan showed dense nodules and calcification in the middle lobe of the right lung. Ultrathin bronchoscopy demonstrates calcification of the distal bronchus of the lateral middle lobe of the right lung. The symptoms were relieved after the removal of the calculi by electronic bronchoscopy. CONCLUSIONS: It is necessary to pay attention to the calcification of the trachea and the differential diagnosis of lung cancer, especially when the level of carcinoembryonic antigen is increased.