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1.
J Med Virol ; 96(6): e29757, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38899432

ABSTRACT

No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in the treatment of long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC-MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest-high-resolution CT (HRCT) images and laboratory parameters were analyzed. During UC-MSCs treatment and follow-up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC-MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class-switched B-cells, and nonswitched B-cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)-6 after UMSCT, while tumor necrosis factor (TNF)-α, IL-17A, and IL-10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS-CoV-2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12-month follow-up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Umbilical Cord , Humans , COVID-19/therapy , COVID-19/immunology , Mesenchymal Stem Cell Transplantation/methods , Male , Female , Middle Aged , Umbilical Cord/cytology , Mesenchymal Stem Cells , Aged , Treatment Outcome , Adult , SARS-CoV-2 , T-Lymphocytes, Regulatory/immunology , B-Lymphocytes/immunology , Interleukin-6/blood
2.
J Magn Reson Imaging ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886922

ABSTRACT

BACKGROUND: Restriction spectrum imaging (RSI), as an advanced quantitative diffusion-weighted magnetic resonance imaging technique, has the potential to distinguish primary benign and malignant lung lesions. OBJECTIVE: To explore how well the tri-compartmental RSI performs in distinguishing primary benign from malignant lung lesions compared with diffusion-weighted imaging (DWI), and to further explore whether positron emission tomography/magnetic resonance imaging (PET/MRI) can improve diagnostic efficacy. STUDY TYPE: Prospective. POPULATION: 137 patients, including 108 malignant and 29 benign lesions (85 males, 52 females; average age = 60.0 ± 10.0 years). FIELD STRENGTH/SEQUENCE: T2WI, T1WI, multi-b value DWI, MR-based attenuation correction, and PET imaging on a 3.0 T whole-body PET/MR system. ASSESSMENT: The apparent diffusion coefficient (ADC), RSI-derived parameters (restricted diffusion f 1 $$ {f}_1 $$ , hindered diffusion f 2 $$ {f}_2 $$ , and free diffusion f 3 $$ {f}_3 $$ ) and the maximum standardized uptake value (SUVmax) were calculated and analyzed for diagnostic efficacy individually or in combination. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, receiver operating characteristic (ROC) curves, Delong test, Spearman's correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The f 1 $$ {f}_1 $$ , SUVmax were significantly higher, and f 3 $$ {f}_3 $$ , ADC were significantly lower in the malignant group [0.717 ± 0.131, 9.125 (5.753, 13.058), 0.194 ± 0.099, 1.240 (0.972, 1.407)] compared to the benign group [0.504 ± 0.236, 3.390 (1.673, 6.030), 0.398 ± 0.195, 1.485 ± 0.382]. The area under the ROC curve (AUC) values ranked from highest to lowest as follows: AUC (SUVmax) > AUC ( f 3 $$ {f}_3 $$ ) > AUC ( f 1 $$ {f}_1 $$ ) > AUC (ADC) > AUC ( f 2 $$ {f}_2 $$ ) (AUC = 0.819, 0.811, 0.770, 0.745, 0549). The AUC (AUC = 0.900) of the combined model of RSI with PET was significantly higher than that of either single-modality imaging. CONCLUSION: RSI-derived parameters ( f 1 $$ {f}_1 $$ , f 3 $$ {f}_3 $$ ) might help to distinguish primary benign and malignant lung lesions and the discriminatory utility of f 2 $$ {f}_2 $$ was not observed. The RSI exhibits comparable or potentially enhanced performance compared with DWI, and the combined RSI and PET model might improve diagnostic efficacy. TECHNICAL EFFICACY: Stage 2.

3.
Ann Diagn Pathol ; 69: 152261, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38262192

ABSTRACT

BACKGROUND: Pathology is considered the gold standard for the diagnosis of lung lesions, but the pathological result is relatively lagging and cannot provide real-time guidance for the biopsy procedure. OBJECTIVE: To investigate the potential application of rapid on-site evaluation (ROSE) during flexible bronchoscopy (FB) in the evaluation and diagnosis of lung lesions. PATIENTS AND METHODS: Consecutive patients who underwent FB for the diagnosis of lung lesions between August 2022 and February 2023 were included in this retrospective study. 294 patients underwent FB with ROSE, while 304 patients underwent FB without ROSE. The final pathological results and the number of patients undergoing repeat biopsies were recorded in both groups. Specifically, we conducted separate statistical analysis for patients undergoing different biopsy methods, including the endobronchial biopsy (EBB), radial probe endobronchial ultrasound transbronchial lung biopsy with guide sheath (r-EBUS-GS-TBLB), and the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to study the detailed roles that ROSE plays under different biopsy methods. RESULTS: The adequacy rate of biopsy specimens from the non-ROSE group was significantly lower than that of the ROSE group (259/281 = 92.17 % vs. 263/268 = 98.13 %, p = 0.001). Meanwhile, fewer patients underwent repeat biopsies in the ROSE group compared to the non-ROSE group (2/294 = 0.68 % vs. 10/304 = 3.29 %, p = 0.023). For the ROSE group, the consistency between ROSE diagnoses and final pathological diagnoses was 94.40 % (κ = 0.886), with 95.58 % for benign diseases and 93.55 % for malignant diseases. CONCLUSION: The utility of ROSE during FB increases the adequacy rate of biopsy specimens and thus decreases the need for repeat biopsies in patients with lung lesions to get a definite diagnosis. Moreover, the high consistency between ROSE diagnoses and final pathological diagnoses suggests that ROSE is a reliable tool for optimizing the diagnosis of lung lesions.


Subject(s)
Bronchoscopy , Lung Neoplasms , Humans , Bronchoscopy/methods , Rapid On-site Evaluation , Retrospective Studies , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology
4.
J Xray Sci Technol ; 32(2): 379-394, 2024.
Article in English | MEDLINE | ID: mdl-38217628

ABSTRACT

Purpose: This study aims to assess the dosimetry and treatment efficiency of TaiChiB-based Stereotactic Body Radiotherapy (SBRT) plans applying to treat two-lung lesions with one overlapping organs at risk. Methods: For four retrospective patients diagnosed with two-lung lesions each patient, four treatment plans were designed including Plan Edge, TaiChiB linac-based, RGS-based, and a linac-RGS hybrid (Plan TCLinac, Plan TCRGS, and Plan TCHybrid). Dosimetric metrics and beam-on time were employed to evaluate and compare the TaiChiB-based plans against Plan Edge. Results: For Conformity Index (CI), Plan TCRGS outperformed all other plans with an average CI of 1.06, as opposed to Plan Edge's 1.33. Similarly, for R50 %, Plan TCRGS was superior with an average R50 % of 3.79, better than Plan Edge's 4.28. In terms of D2 cm, Plan TCRGS also led with an average of 48.48%, compared to Plan Edge's 56.25%. For organ at risk (OAR) sparing, Plan TCRGS often displayed the lowest dosimetric values, notably for the spinal cord (Dmax 5.92 Gy) and lungs (D1500cc 1.00 Gy, D1000cc 2.61 Gy, V10 Gy 15.14%). However, its high Dmax values for the heart and great vessels sometimes exceeded safety thresholds. Plan TCHybrid presented a balanced approach, showing doses comparable to or better than Plan Edge without crossing safety limits. In terms of beam-on time, Plan TCLinac emerged as the most efficient treatment option in three out of four cases, followed closely by Plan Edge in one case. Plan TCRGS, despite its dosimetric advantages, was the least efficient, recording notably longer beam-on times, with a peak at 33.28 minutes in Case 2. Conclusion: For patients with two-lung lesions treated by SBRT whose one lesion overlaps with OARs, the Plan TCHybrid delivered by TaiChiB digital radiotherapy system can be recommended as a clinical option.


Subject(s)
Lung Neoplasms , Radiosurgery , Radiotherapy, Intensity-Modulated , Humans , Lung Neoplasms/radiotherapy , Lung Neoplasms/pathology , Retrospective Studies , Organs at Risk , Radiotherapy Planning, Computer-Assisted , Radiotherapy Dosage , Lung/pathology , Etoposide
5.
Int Microbiol ; 26(4): 893-906, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36933182

ABSTRACT

Low microbial biomass in the lungs, high host-DNA contamination and sampling difficulty limit the study on lung microbiome. Therefore, little is still known about lung microbial communities and their functions. Here, we perform a preliminary exploratory study to investigate the composition of swine lung microbial community using shotgun metagenomic sequencing and compare the microbial communities between healthy and severe-lesion lungs. We collected ten lavage-fluid samples from swine lungs (five from healthy lungs and five from severe-lesion lungs), and obtained their metagenomes by shotgun metagenomic sequencing. After filtering host genomic DNA contamination (93.5% ± 1.2%) in the lung metagenomic data, we annotated swine lung microbial communities ranging from four domains to 645 species. Compared with previous taxonomic annotation of the same samples by the 16S rRNA gene amplicon sequencing, it annotated the same number of family taxa but more genera and species. We next performed an association analysis between lung microbiome and host lung-lesion phenotype. We found three species (Mycoplasma hyopneumoniae, Ureaplasma diversum, and Mycoplasma hyorhinis) were associated with lung lesions, suggesting they might be the key species causing swine lung lesions. Furthermore, we successfully reconstructed the metagenome-assembled genomes (MAGs) of these three species using metagenomic binning. This pilot study showed us the feasibility and relevant limitations of shotgun metagenomic sequencing for the characterization of swine lung microbiome using lung lavage-fluid samples. The findings provided an enhanced understanding of the swine lung microbiome and its role in maintaining lung health and/or causing lung lesions.


Subject(s)
Metagenome , Microbiota , Swine , Pilot Projects , RNA, Ribosomal, 16S/genetics , Microbiota/genetics , Lung/microbiology , Metagenomics , Animals
6.
BMC Pulm Med ; 23(1): 432, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37940942

ABSTRACT

BACKGROUND: We assessed the performance of Electromagnetic navigational bronchoscopy (ENB) as a standalone diagnostic technique and the performance of different sampling tools used during the procedure. METHODS: We recruited 160 consecutive patients who underwent ENB for peripheral lung lesions (PLL) at a tertiary care centre. The diagnostic performance of ENB and sampling tools was assessed using a logistic regression model and a ROC-curve in which the dependent variable was diagnostic success. A multivariate model was built to predict diagnostic success before performing ENB to select the best candidates for the procedure. RESULTS: Most patients with PLLs in the study were male (65%), with a mean age of 67.9 years. The yield was 66% when the most common techniques were used together as suction catheter + transbronchial biopsy forceps (TBBx) + bronchoalveolar lavage + bronchial washing (p < 0.001) and increased to 69% when transbronchial needle aspiration (TBNA) and cytology brush were added (p < 0.001). Adding diagnostic techniques such as TBBx and TBNA resulted in an increase in diagnostic performance, with a statistically significant trend (p = 0.002). The logistic model area-under the ROC-curve for diagnostic success during ENB was 0.83 (95% CI:0.75-0.90; p < 0.001), and a logit value ≥ 0.12 was associated with ≥ 50% probability of diagnostic success. CONCLUSIONS: ENB, as a stand-alone diagnostic tool for the evaluation of PLLs when performed by experienced operators using a multi-modality technique, has a good diagnostic yield. The probability of having a diagnostic ENB could be assessed using the proposed model.


Subject(s)
Bronchoscopy , Lung Neoplasms , Humans , Male , Aged , Female , Bronchoscopy/methods , Electromagnetic Phenomena , Biopsy/methods , Catheterization , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology
7.
BMC Pulm Med ; 22(1): 270, 2022 Jul 14.
Article in English | MEDLINE | ID: mdl-35836220

ABSTRACT

BACKGROUND: Despite being minimally invasive, bronchoscopy does not always result in pathological specimens being obtained. Therefore, we investigated whether virtual bronchoscopic navigation (VBN) findings were associated with the rate of diagnosis of primary lung cancer by bronchoscopy in patients with peripheral lung lesions. METHODS: This study included patients with suspected malignant peripheral lung lesions who underwent bronchoscopy at St. Luke's International Hospital between October 2013 and March 2020. Patients diagnosed with primary lung cancer were grouped according to whether their pathology could be diagnosed by bronchoscopy, and their clinical factors were compared. In addition, the distance between the edge of the lesion and the nearest branch ("distance by VBN") was calculated. The distance by VBN and various clinical factors were compared with the diagnostic rates of primary lung cancer. RESULTS: The study included 523 patients with 578 lesions. After excluding 55 patients who underwent multiple bronchoscopies, 381 patients were diagnosed with primary lung cancer. The diagnostic rate by bronchoscopy was 71.1% (271/381). Multivariate analysis revealed that the lesion diameter (odds ratio [OR] 1.107), distance by VBN (OR 0.94) and lesion structure (solid lesion or ground-glass nodule; OR 2.988) influenced the risk of a lung cancer diagnosis. The area under the receiver operating characteristic curve for diagnosis based on lesion diameter and distance by VBN was 0.810. CONCLUSION: The distance by VBN and lesion diameter were predictive of the diagnostic rates of primary lung cancer by bronchoscopy in patients with peripheral lung lesions.


Subject(s)
Bronchoscopy , Lung Neoplasms , Humans , Lung/diagnostic imaging , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology
8.
BMC Surg ; 22(1): 203, 2022 May 25.
Article in English | MEDLINE | ID: mdl-35614417

ABSTRACT

OBJECTIVE: To investigate the efficacy and safety of simultaneous subxiphoid single-port thoracoscopic resection of bilateral lung lesions. METHODS: This retrospective study analyzed the clinical data of 72 patients who underwent resection of bilateral lung lesions at the Department of Thoracic Surgery in the First Affiliated Hospital of University of Science and Technology of China between August 2020 and January 2022. Surgery-related parameters were compared between patients who underwent subxiphoid single-port thoracoscopy (subxiphoid group, 36 patients) and patients who underwent intercostal single-port thoracoscopy (intercostal group, 36 patients). RESULTS: Compared to the intercostal group, the subxiphoid group exhibited significantly better postoperative catheterization time (P = 0.013), postoperative thoracic drainage, postoperative visual analog scale pain scores at 24 and 48 h, and incision pain and numbness at 1 and 3 months after surgery (all P < 0.05). There were no significant differences in operation time, intraoperative blood loss, or postoperative complications between the two groups (all P > 0.05). There were no cases of perioperative mortality, conversion to thoracotomy, or serious complications in either group. CONCLUSION: Subxiphoid single-port thoracoscopic surgery for simultaneous resection of bilateral lung lesions is safe and effective, reduces postoperative acute and chronic pain, decreases trauma, allows faster recovery, and is more consistent with the concept of minimally invasive surgery than bilateral intercostal single-port thoracoscopy. Thus, this subxiphoid single-port thoracoscopic surgery approach should be considered for clinical application.


Subject(s)
Pneumonectomy , Thoracic Surgery, Video-Assisted , Humans , Lung , Pain , Retrospective Studies
9.
Eur J Nucl Med Mol Imaging ; 48(2): 584-591, 2021 02.
Article in English | MEDLINE | ID: mdl-32719914

ABSTRACT

BACKGROUND: The use of hybrid PET/MRI for clinical staging is growing in several cancer forms and, consequently, PET/MRI has also gained interest in the assessment of non-small cell lung cancer (NSCLC) and lung lesions. However, lung evaluation with PET/MRI is associated with challenges related to technical issues and diagnostic image quality. We, therefore, investigated the published literature on PET/MRI for clinical staging in NSCLC or lung nodule detection specifically addressing diagnostic accuracy and technical issues. METHODS: The data originates from a systematic search performed in PubMed/MEDLINE, Embase, and Cochrane Library on hybrid PET/MRI in patients with cancer for a scoping review published earlier ( https://doi.org/10.1007/s00259-019-04402-8 ). Studies in English and German evaluating the diagnostic performance of hybrid PET/MRI for NSCLC or lung nodule detection in cancer patients were selected. Data reported in peer-reviewed journals without restrictions to year of publication were included. RESULTS: A total of 3138 publications were identified from which 116 published 2012-2018 were included. Of these, nine studies addressed PET/MRI in NSCLC (4) or lung nodule detection (5). Overall, PET/MRI did not provide advantages in preoperative T- and N-staging in NSCLC compared to PET/CT. The data on M-staging were too few for conclusions to be drawn. The lung nodule detection rate of PET/MRI was comparable to that of PET/CT for FDG-avid nodules larger than 10 mm, but the sensitivity of PET/MRI for detection of non-FDG-avid nodules smaller than 5 mm was low. CONCLUSION: PET/MRI did not provide advantages in T- and N-staging of NSCLC compared to PET/CT. PET/MRI had a comparable sensitivity for detection of FDG-avid lung nodules and nodules over 10 mm, but PET/CT yielded a higher detection rate in non FDG-avid lung nodules under 5 mm. With PET/MRI, the overall detection rate for lung nodules in various cancer types remains inferior to that of PET/CT due to the lower diagnostic performance of MRI than CT in the lungs.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Fluorodeoxyglucose F18 , Humans , Lung/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Magnetic Resonance Imaging , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography , Sensitivity and Specificity , Tomography, X-Ray Computed
10.
Adv Exp Med Biol ; 1324: 35-40, 2021.
Article in English | MEDLINE | ID: mdl-33346903

ABSTRACT

Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated disorder with necrotic vasculitis of small- and medium-size arteries and veins. In the literature, there are many case reports of patients with GPA of different, sometimes unusual, clinical manifestations. In this paper, we present difficulties that accompanied the process of diagnosing GPA in a 54-year-old symptomatic patient who was. Computer tomography scans showed numerous tumor-like lesions of various and irregular sizes in both lungs. Positron emission tomography scans suggested a lymphoproliferative disease, otherwise failing to provide a clue concerning its nature or localization. After a series of diagnostic twists and turns, inclusive of bronchoalveolar lavage, cervical mediastinoscopy, paratracheal lymph biopsy, and histopathologic examinations, and other tests, the diagnosis of GPA was established as the most probable. The patient was acutely treated with loading doses of methylprednisolone and cyclophosphamide, gradually tapered off during the long-term follow-up. He was discharged from the hospital in a good condition. We conclude that GPA is an uncommon disease with indistinctive signs, which raises the risk of its being overlooked. A diagnostic algorithm is required for patients with suspected GPA. A timely diagnosis is essential as the disease may quickly progress into renal or multiorgan dysfunction, and ultimately lead to death if untreated. Pulmonary involvement may also suggest neoplastic changes.


Subject(s)
Granulomatosis with Polyangiitis , Antibodies, Antineutrophil Cytoplasmic , Biopsy , Granulomatosis with Polyangiitis/diagnostic imaging , Humans , Lung , Male , Middle Aged , Tomography, X-Ray Computed
11.
Rev Med Liege ; 76(5-6): 440-445, 2021 May.
Article in French | MEDLINE | ID: mdl-34080377

ABSTRACT

Lung cancer remains the deadliest cancer. It is the result of genetic aberrations in the cells of the respiratory tract exposed to carcinogenic agents, responsible for their anarchic multiplication. It is necessary to study these abnormalities in order to better understand the early stages and the mechanisms of evolution, thereby to establish new screening, monitoring and treatment strategies. The NELSON study confirms that systematic screening for lung cancer in target populations leads to a reduction in mortality from this disease. Despite this, there is currently no consensus in Belgium between medical experts and politicians for systematic lung cancer screening.


Le cancer pulmonaire reste le cancer le plus mortel. Il est le résultat d'aberrations génétiques au niveau de cellules des voies respiratoires exposées aux agents carcinogènes, responsables de leur multiplication anarchique. Il est nécessaire d'étudier ces anomalies pour mieux comprendre les stades précoces et les mécanismes d'évolution afin d'établir de nouvelles stratégies de dépistage, de suivi et de traitement. L'étude NELSON confirme qu'un dépistage systématique des cancers pulmonaires de populations cibles permet une diminution de la mortalité liée à cette pathologie. Malgré cela, il n'y a, actuellement, pas de consensus en Belgique entre les experts médicaux et le monde politique pour un dépistage systématique du cancer pulmonaire.


Subject(s)
Early Detection of Cancer , Lung Neoplasms , Belgium , Humans , Lung , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Mass Screening , Tomography, X-Ray Computed
12.
IEEE Trans Industr Inform ; 17(9): 6528-6538, 2021 Sep.
Article in English | MEDLINE | ID: mdl-37981911

ABSTRACT

Automatic segmentation of lung lesions from COVID-19 computed tomography (CT) images can help to establish a quantitative model for diagnosis and treatment. For this reason, this article provides a new segmentation method to meet the needs of CT images processing under COVID-19 epidemic. The main steps are as follows: First, the proposed region of interest extraction implements patch mechanism strategy to satisfy the applicability of 3-D network and remove irrelevant background. Second, 3-D network is established to extract spatial features, where 3-D attention model promotes network to enhance target area. Then, to improve the convergence of network, a combination loss function is introduced to lead gradient optimization and training direction. Finally, data augmentation and conditional random field are applied to realize data resampling and binary segmentation. This method was assessed with some comparative experiment. By comparison, the proposed method reached the highest performance. Therefore, it has potential clinical applications.

13.
Ter Arkh ; 93(2): 199-203, 2021 Feb 15.
Article in Russian | MEDLINE | ID: mdl-36286637

ABSTRACT

Mesalazine is a main medicine for treatment of ulcerative colitis. Most patience of left-sides and total colitis receive oral mesalazine for many years. Currently, there is a little information about the tolerability and safety of long-term use of mesalazine. The eosinophilic pneumonia, organizing pneumonia, and nonspecific interstitial pneumonia are very rare adverse effects of ulcerative colitis treatment with mesalazine. The article presents case of the development interstitial lung disease induced by mesalazine under long-term maintenance treatment for three years in the young patient with ulcerative colitis. It shows the difficulties in diagnosing this disease due to the work-long low-grade fever in manifestation of pneumonitis, the similarity of clinical and radiological manifestations (diffuse bilateral pattern in chest imaging). The article demonstrates the limitations of modern laboratory and instrumental diagnostic methods for the differentiation of disseminated lesions of the lung tissue, and shows the importance of elimination treatment of mesalazine-induced pneumonitis.

14.
Am J Physiol Lung Cell Mol Physiol ; 319(5): L794-L809, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32726135

ABSTRACT

Lung injury in mice induces mobilization of discrete subsets of epithelial progenitor cells to promote new airway and alveolar structures. However, whether similar cell types exist in human lung remains unresolved. Using flow cytometry, we identified a distinct cluster of cells expressing the epithelial cell adhesion molecule (EpCAM), a cell surface marker expressed on epithelial progenitor cells, enriched in the ecto-5'-nucleotidase CD73 in unaffected postnatal human lungs resected from pediatric patients with congenital lung lesions. Within the EpCAM+CD73+ population, a small subset coexpresses integrin ß4 and HTII-280. This population remained stable with age. Spatially, EpCAM+CD73+ cells were positioned along the basal membrane of respiratory epithelium and alveolus next to CD73+ cells lacking EpCAM. Expanded EpCAM+CD73+ cells give rise to a pseudostratified epithelium in a two-dimensional air-liquid interface or a clonal three-dimensional organoid assay. Organoids generated under alveolar differentiation conditions were cystic-like and lacked robust alveolar mature cell types. Compared with unaffected postnatal lung, congenital lung lesions were marked by clusters of EpCAM+CD73+ cells in airway and cystic distal lung structures lined by simple epithelium composed of EpCAM+SCGB1A1+ cells and hyperplastic EpCAM+proSPC+ cells. In non-small-cell lung cancer (NSCLC), there was a marked increase in EpCAM+CD73+ tumor cells enriched in inhibitory immune checkpoint molecules CD47 and programmed death-ligand 1 (PD-L1), which was associated with poor survival in lung adenocarcinoma (LUAD). In conclusion, EpCAM+CD73+ cells are rare novel epithelial progenitor cells in the human lung. Importantly, reemergence of CD73 in lung adenocarcinoma enriched in negative immune checkpoint molecules may serve as a novel therapeutic target.


Subject(s)
5'-Nucleotidase/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Epithelial Cells/metabolism , Stem Cells/cytology , Animals , Cell Differentiation/physiology , Epithelial Cell Adhesion Molecule/metabolism , Humans , Lung/pathology , Lung Neoplasms/metabolism , Mesenchymal Stem Cells/metabolism , Mice
15.
J Ultrasound Med ; 38(9): 2361-2372, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30653685

ABSTRACT

OBJECTIVES: To assess the diagnostic performance of the fetal cardiac axis (CA) and/or cardiac position (CP) versus the congenital pulmonary malformation volume ratio (CVR) in predicting any and severe neonatal respiratory morbidity in fetal congenital lung lesions. METHODS: This work was an 11-year retrospective cohort study. The sensitivity, specificity, positive predictive value, and negative predictive value of CA and/or CP assessment in prediction of respiratory morbidity were calculated before 24 weeks' gestation and between 24 and 32 weeks and compared to CVR cutoffs obtained from the literature. RESULTS: Fifty-three patients were included. CA and/or CP abnormalities were present in 45% and 38% of patients before 24 weeks and between 24 and 32 weeks and were significantly more common in left- versus right-sided lesions (60% versus 17%; P = .003). The sensitivity, specificity, positive predictive value, and negative predictive value of an abnormal CA and/or CP for any and severe respiratory morbidity were 0.67, 0.61, 0.33, and 0.86 and 0.8, 0.58, 0.17, and 0.97 before 24 weeks and 0.75, 0.73, 0.45, and 0.91 and 0.8, 0.67, 0.20, and 0.97 between 24 and 32 weeks, respectively. An abnormal CA and/or CP had higher sensitivity for any respiratory morbidity compared to the CVR at 0.5 and 0.8 cutoffs both before 24 weeks and between 24 and 32 weeks (P < .05). CONCLUSIONS: An abnormal CA and/or CP before 24 weeks and between 24 and 32 weeks has higher sensitivity for the detection of any respiratory morbidity at birth compared to the CVR at both 0.5 and 0.8 cutoffs. A normal CA and CP have a high negative predictive value for excluding any respiratory morbidity at birth both before 24 weeks and between 24 and 32 weeks.


Subject(s)
Fetal Heart/anatomy & histology , Lung Diseases/congenital , Lung Diseases/diagnosis , Lung/embryology , Lung/physiopathology , Ultrasonography, Prenatal/methods , Adult , Cohort Studies , Female , Humans , Lung Diseases/physiopathology , Pregnancy , Retrospective Studies , Sensitivity and Specificity , Young Adult
16.
Paediatr Anaesth ; 28(11): 1035-1042, 2018 11.
Article in English | MEDLINE | ID: mdl-30281181

ABSTRACT

BACKGROUND: Video-assisted thoracoscopic surgery has dramatically increased over the last decade because of both medical and cosmetic benefits. Anesthesia for video-assisted thoracoscopic surgery in small children is more challenging compared to adults due to the considerable problems posed by small airway dimensions and ventilation. The optimal technique for one-lung ventilation has yet to be established and the use of remifentanil infusion in this setting is not well described. AIMS: This study investigated the use of extraluminal bronchial blocker placement for one-lung ventilation and the effect of infusion of remifentanil in infants and small children undergoing video-assisted thoracoscopic surgery. METHODS: We retrospectively reviewed the technique of one-lung ventilation and the hemodynamic effects of remifentanil infusion in 31 small children during elective video-assisted thoracoscopic surgery for congenital lung lesions under anesthesia with sevoflurane or isoflurane, oxygen, and air. Patients' heart rate, blood pressure, and endtidal carbon dioxide at baseline (after induction of anesthesia), immediately after one-lung ventilation, during carbon dioxide insufflation, and at the end of one-lung ventilation were extracted from the database and analyzed. The use of vasopressors or dexmedetomidine was also recorded and analyzed. RESULTS: Extraluminal placement of a bronchial blocker alongside the tracheal tube was successfully performed in 90.3% of cases (28 patients) without any serious complications or arterial oxygen desaturation. There was no significant rise in blood pressure or heart rate even with the rise of endtidal carbon dioxide concentration during video-assisted thoracoscopic surgery. In 58% of patients (18 patients), phenylephrine was administered to maintain the blood pressure within 20% of the baseline value. There was no significant change in the heart rate of all patients at each time point. CONCLUSION: One-lung ventilation with an extraluminal parallel blocker was used effectively in this series of young children undergoing thoracoscopic excision of congenital pulmonary lesions. Remifentanil infusion attenuated surgical stress effectively in infants and small children undergoing video-assisted thoracoscopic surgery.


Subject(s)
Airway Management/methods , Analgesics, Opioid/therapeutic use , Anesthesia, General/methods , One-Lung Ventilation/methods , Remifentanil/therapeutic use , Thoracic Surgery, Video-Assisted/methods , Child, Preschool , Cystic Adenomatoid Malformation of Lung, Congenital/surgery , Female , Hemodynamics/drug effects , Humans , Infant , Intubation, Intratracheal/methods , Male , Retrospective Studies , Sevoflurane/therapeutic use , Thoracotomy/methods
17.
Histopathology ; 70(7): 1114-1124, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28207938

ABSTRACT

AIMS: The lung lesion [immunoglobulin (Ig)G4-L] of IgG4-related disease (IgG4-RD) is a condition that occurs together with IgG4-RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD-L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data. METHODS AND RESULTS: Nine patients had IgG4-L (high levels of serum IgG4 and of IgG4+ cells in lung specimens; typical extrapulmonary manifestations). Fifteen patients had iMCD-L (polyclonal hyperimmunoglobulinaemia, elevated serum interleukin-6 levels and polylymphadenopathy with typical lymphadenopathic lesions). Mean values for age, serum haemoglobin levels and IgG4/IgG ratios were higher in the IgG4-L group and C-reactive protein levels were higher in the iMCD-L group. All IgG4-RD lung lesions showed myxomatous granulation-like fibrosis (active fibrosis), with infiltration of lymphoplasmacytes and scattered eosinophils within the perilymphatic stromal area, such as interlobular septa and pleura with obstructive vasculitis. All 15 lung lesions of iMCD, however, had marked accumulation of polyclonal lymphoplasmacytes in lesions with lymphoid follicles and dense fibrosis, mainly in the alveolar area adjacent to interlobular septa and pleura without obstructive vasculitis. CONCLUSIONS: Although both lesions had lymphoplasmacytic infiltration, lung lesions of IgG4-RD were characterized by active fibrosis with eosinophilic infiltration within the perilymphatic stromal area with obstructive vasculitis, whereas lung lesions of iMCD had lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to the perilymphatic stromal area. These clinicopathological features may help to differentiate the two diseases.


Subject(s)
Castleman Disease/pathology , Immunoglobulin G , Lung Diseases/pathology , Adult , Aged , Female , Humans , Male , Middle Aged
18.
Adv Exp Med Biol ; 1022: 35-43, 2017.
Article in English | MEDLINE | ID: mdl-28573444

ABSTRACT

Fever of unknown origin (FUO) remains one of the most difficult diagnostic challenges. The causes of FUO can be various diseases located in different organs. The aim of the study was to determine the prevalence and nature of pulmonary lesions during FUO. One hundred and sixty one patients with FUO participated in this prospective study. We performed a detailed comprehensive history, physical examination, and a wide spectrum of tests. The most common causes of FUO were infections (39%), autoimmune conditions (28%), and neoplasms (17%). Lung lesions were found in 30% of patients. In this group 35% were infections, 30% autoimmune diseases, and 4% cancer. Among patients with respiratory infections, there were cases of tuberculosis, atypical pneumonia, lung abscess, and bronchiectases. Autoimmune pulmonary lesions were observed during vasculitis and systemic lupus. The causes of FUO in the group of patients with lung lesions were also pulmonary embolism, sarcoidosis, and pulmonary fibrosis. Chest CT played an important role in the diagnosis of the causes of FUO with pulmonary manifestations. Pulmonary lesions are a common cause of FUO. Most FUO with pulmonary lesions are recognized during infections and autoimmune diseases. An important part of diagnosing FUO is a detailed evaluation of the respiratory system.


Subject(s)
Fever of Unknown Origin/diagnostic imaging , Lung/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Radiography, Thoracic , Tomography, X-Ray Computed , Young Adult
19.
Acta Vet Hung ; 65(3): 354-365, 2017 09.
Article in English | MEDLINE | ID: mdl-28956483

ABSTRACT

The aim of this study was to determine the association of lung lesions with carcass and meat quality traits in slaughter pigs and to describe the main morphological features associated with lung lesions. Macroscopic lesions on the lungs were detected in 67.09% of a total of 79 pigs examined. Histopathological examination revealed that acute and chronic interstitial pneumonia represented the commonest changes, detected in 26.67% and 33.33% of the cases, respectively. Bronchopneumonia was found in 33.33% of the cases. By immunohistochemical examination, 26.67% of the lungs showed the presence of severe peribronchiolar and perialveolar infiltration composed predominantly of CD3+ T lymphocytes, which finding may be indicative of viral pneumonia. Regarding the production traits, it was confirmed that pigs with severe lung lesions had the lowest liveweight, hot carcass weight and meatiness, the highest pH value 45 min after slaughtering (pH45) and the highest incidence of dark, firm, dry (DFD) and pale, soft, exudative (PSE) meat. The presence of lung lesions significantly downgraded carcass value and caused a significant deterioration in pork quality.


Subject(s)
Body Composition , Lung Diseases/veterinary , Meat/standards , Swine Diseases/pathology , Animals , Body Weight , Lung Diseases/pathology , Swine
20.
Colorectal Dis ; 17(10): O184-90, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26201822

ABSTRACT

AIM: This study evaluated the accuracy of chest computed tomography (CCT) in the preoperative staging of patients with potentially resectable colorectal cancer (CRC). An attempt was made to determine whether CCT has a significant influence on management and clinical outcome. METHOD: A review was conducted of all preoperative CCTs and X-rays performed in patients submitted to elective resection of CRC at our institution between 2005 and 2012. All scans were revised by an independent radiologist who was unaware of the circumstances of each case. The findings were classified as benign, malignant or indeterminate. Patients were followed for at least 12 months after surgery to assess the clinical evolution of any lesion found on CCT and the oncological outcome. RESULTS: Two hundred and twenty-three patients were included. The CCT showed normal or benign findings in 157 (70.4%) patients, a malignant lesion in 17 (7.6%), and an indeterminate lung lesion (ILL) in 49 (22%). Of the 30 patients with proven lung metastases, a plain X-ray detected lesions in only 11 (36.7%) patients. During the postoperative follow-up, 14 (28.6%) of the 49 patients with ILL demonstrated malignant progression of the lung lesions. Among all 223 patients, only six (2.7%) underwent lung resection. CONCLUSION: CCT is superior to plain X-ray for the detection of lung metastases. Despite the medical and financial implications of preoperative CCT, only a small number of patients will eventually undergo lung resection. We call into question the role of routine CCT in the staging of patients with CRC. A more selective approach, reserving CT for patients at high risk of lung metastases, is suggested.


Subject(s)
Adenocarcinoma/surgery , Colorectal Neoplasms/surgery , Elective Surgical Procedures/methods , Lung Neoplasms/diagnostic imaging , Radiography, Thoracic/statistics & numerical data , Tomography, X-Ray Computed/statistics & numerical data , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Brazil , Cohort Studies , Colorectal Neoplasms/pathology , Female , Humans , Lung Neoplasms/secondary , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Preoperative Care/methods , Prognosis , Radiography, Thoracic/methods , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Survival Analysis , Tomography, X-Ray Computed/methods , Treatment Outcome , Unnecessary Procedures/statistics & numerical data
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