Lung Lesions Research Articles

Understanding the Landscape of Bronchoscopy in Lung Cancer: Insights From Lesion Location, Gender, and Diagnostic Efficacy.

Lung cancer constitutes a critical global health concern. According to the International Agency for Research on Cancer's (IARC) GLOBOCAN 2020 estimates, lung canceris the leading cause of death in cancer patients. In areas where tuberculosis is prevalent, misdiagnosis and mistreatment frequently result from overlap, creating significant difficulties that delay diagnosis and treatment. Amid this complication, bronchoscopic techniques emerge as critical diagnostic tools, though their efficacy varies between studies. Our retrospective study, conducted from July 2021 to December 2022at the Department of Respiratory Medicine, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, examined 156 participants withmalignancies. Our focus encompassed diverse lesions within the bronchial landscape, revealing intriguing findings. Bronchoscopic examinations unravelled prevalent abnormalities: 52 (33.3%) manifested as intraluminal growth, 48 (31.6%) as mucosal irregularities, and a less frequent (16, 10.3%) as an intraluminal bulge. Transbronchial needle aspiration stood out with a 10/11 (91%) positivity rate, biopsy came in second at 38/46 (83%), and bronchoalveolar lavage showed a 44/152 (29%) positivity rate.It was interesting to see how the lesions were spread out among the different types of histology. For example, squamous cell carcinoma showed 17/37 (46%) intraluminal growth, while adenocarcinoma showed 22/60 (36.7%) intraluminal growth and 4/60 (6.7%) intraluminal bulge. Moreover, a significant absence of abnormalities was observed in various lesions, underlining the intricacies of characterising bronchial lesions. Our study shows that direct tissue sampling is better and that new bronchoscopic technologies are important for diagnosing lesions that were hard to get to in the past. However, limitations in patient selection biases and the single-centre focus caution against generalised interpretations. Our research illuminates the pivotal role of bronchoscopic methods in diagnosing lung lesions, emphasising the necessity for continued advancements to enhance diagnostic accuracy and treatment efficacy in lung cancer subtypes.

Identification of Precise 3D CT Radiomics for Habitat Computation by Machine Learning in Cancer.

Purpose To identify precise three-dimensional radiomics features in CT images that enable computation of stable and biologically meaningful habitats with machine learning for cancer heterogeneity assessment. Materials and Methods This retrospective study included 2436 liver or lung lesions from 605 CT scans (November 2010-December 2021) in 331 patients with cancer (mean age, 64.5 years ± 10.1 [SD]; 185 male patients). Three-dimensional radiomics were computed from original and perturbed (simulated retest) images with different combinations of feature computation kernel radius and bin size. The lower 95% confidence limit (LCL) of the intraclass correlation coefficient (ICC) was used to measure repeatability and reproducibility. Precise features were identified by combining repeatability and reproducibility results (LCL of ICC ≥ 0.50). Habitats were obtained with Gaussian mixture models in original and perturbed data using precise radiomics features and compared with habitats obtained using all features. The Dice similarity coefficient (DSC) was used to assess habitat stability. Biologic correlates of CT habitats were explored in a case study, with a cohort of 13 patients with CT, multiparametric MRI, and tumor biopsies. Results Three-dimensional radiomics showed poor repeatability (LCL of ICC: median [IQR], 0.442 [0.312-0.516]) and poor reproducibility against kernel radius (LCL of ICC: median [IQR], 0.440 [0.33-0.526]) but excellent reproducibility against bin size (LCL of ICC: median [IQR], 0.929 [0.853-0.988]). Twenty-six radiomics features were precise, differing in lung and liver lesions. Habitats obtained with precise features (DSC: median [IQR], 0.601 [0.494-0.712] and 0.651 [0.52-0.784] for lung and liver lesions, respectively) were more stable than those obtained with all features (DSC: median [IQR], 0.532 [0.424-0.637] and 0.587 [0.465-0.703] for lung and liver lesions, respectively; P < .001). In the case study, CT habitats correlated quantitatively and qualitatively with heterogeneity observed in multiparametric MRI habitats and histology. Conclusion Precise three-dimensional radiomics features were identified on CT images that enabled tumor heterogeneity assessment through stable tumor habitat computation. Keywords: CT, Diffusion-weighted Imaging, Dynamic Contrast-enhanced MRI, MRI, Radiomics, Unsupervised Learning, Oncology, Liver, Lung Supplemental material is available for this article. © RSNA, 2024 See also the commentary by Sagreiya in this issue.

Pulmonary lesions in early response assessment in pediatric Hodgkin lymphoma: prevalence and possible implications for initial staging

BackgroundDisseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for coexistence of non-malignant lung lesions due to infection representing background noise to avoid erroneously upstaging with therapy intensification.ObjectiveThis study attempts to describe new lung lesions detected on interim staging computed tomography (CT) scans after two cycles of vincristine, etoposide, prednisolone, doxorubicin in a prospective clinical trial. Based on the hypothesis that these new lung lesions are not part of the underlying malignancy but are epiphenomena, the aim is to analyze their size, number, and pattern to help distinguish true lung metastases from benign lung lesions on initial staging.Materials and methodsA retrospective analysis of the EuroNet-PHL-C1 trial re-evaluated the staging and interim lung CT scans of 1,300 pediatric patients with HL. Newly developed lung lesions during chemotherapy were classified according to the current Fleischner glossary of terms for thoracic imaging. Patients with new lung lesions found at early response assessment (ERA) were additionally assessed and compared to response seen in hilar and mediastinal lymph nodes.ResultsOf 1,300 patients at ERA, 119 (9.2%) had new pulmonary lesions not originally detectable at diagnosis. The phenomenon occurred regardless of initial lung involvement or whether a patient relapsed. In the latter group, new lung lesions on ERA regressed by the time of relapse staging. New lung lesions on ERA in patients without relapse were detected in 102 (7.8%) patients. Pulmonary nodules were recorded in 72 (5.5%) patients, the majority (97%) being<10 mm. Consolidations, ground-glass opacities, and parenchymal bands were less common.ConclusionNew nodules on interim staging are common, mostly measure less than 10 mm in diameter and usually require no further action because they are most likely non-malignant. Since it must be assumed that benign and malignant lung lesions coexist on initial staging, this benign background noise needs to be distinguished from lung metastases to avoid upstaging to stage IV disease. Raising the cut-off size for lung nodules to ≥ 10 mm might achieve the reduction of overtreatment but needs to be further evaluated with survival data. In contrast to the staging criteria of EuroNet-PHL-C1 and C2, our data suggest that the number of lesions present at initial staging may be less important.

Risk of isolated metastatic disease outside the abdomen is low in cT1a renal cancer: A retrospective analysis of a large cohort from the Scottish Renal Cancer Consortium

Objectives: Chest computed tomography (CT) is recommended by the European Association of Urology guidelines as part of the evaluation of patients presenting with renal tumours. There are no direct recommendations for the use of computed tomography (CT) pelvis, but this is often included routinely in the assessment for metastatic disease. The incidence of metastatic disease in cT1a renal cell carcinoma (RCC) is low. Predictive algorithms may be able to guide the selective use of chest CT in the pre-operative evaluation of patients. We sought primarily to assess the clinical utility of these algorithms in predicting lung and pelvic metastases in a national cohort of purely cT1a tumours. Patients and Methods: Patients with sporadic, unilateral cT1a renal tumours diagnosed between January 2012 and December 2017 were identified from a prospectively collected national database. Patient clinico-pathological parameters and treatment type were recorded. Details on clinical presentation and bloods at diagnosis were taken from local electronic records retrospectively. Differences between those with and without metastatic disease were assessed. Results: Of the total 696 patients, 7 (1.0%) patients had metastatic disease exclusively outside the abdomen. Indeterminate lung lesions were present in 114 (16.6%) patients, with 2 (1.8%) progressing to presumed metastatic disease. Patients with metastatic disease were more likely to be anaemic than those without metastatic disease (85.7% and 25.7%, respectively, p = 0.020). Conclusion: Metastatic disease at presentation with cT1a renal cancer was uncommon in our national multi-centre series, with limited impact on clinical management. Patients with cT1a without intra-abdominal metastatic disease could safely avoid CT chest or pelvic CT at diagnosis, with benefits in terms of radiation exposure and resource utilisation. Level of evidence: 3.

Benign pulmonary metastasizing leiomyomatosis: report of 3 cases and review of the literature

Benign pulmonary metastasizing leiomyomatosis (BPML) is a rare condition, most commonly found in premenopausal women in reproductive age with a history of hysterectomy for uterine leiomyoma or myomectomy. Most cases are asymptomatic and the diagnosis is usually incidental during routine examinations. Although the condition is benign, some patients may present with dyspnea and significant hypoxemia. The diagnosis is established through anatomopathological examination of the lung lesions. Treatment varies according to the clinical picture and the number and size of the lesions.

Self-attention-driven retrieval of chest CT images for COVID-19 assessment

Numerous methods have been developed for computer-aided diagnosis (CAD) of coronavirus disease-19 (COVID-19), based on chest computed tomography (CT) images. The majority of these methods are based on deep neural networks and often act as “black boxes” that cannot easily gain the trust of medical community, whereas their result is uniformly influenced by all image regions. This work introduces a novel, self-attention-driven method for content-based image retrieval (CBIR) of chest CT images. The proposed method analyzes a query CT image and returns a classification result, as well as a list of classified images, ranked according to similarity with the query. Each CT image is accompanied by a heatmap, which is derived by gradient-weighted class activation mapping (Grad-CAM) and represents the contribution of lung tissue and lesions to COVID-19 pathology. Beyond visualization, Grad-CAM weights are employed in a self-attention mechanism, in order to strengthen the influence of the most COVID-19-related image regions on the retrieval result. Experiments on two publicly available datasets demonstrate that the binary classification accuracy obtained by means of DenseNet-201 is 81.3% and 96.4%, for COVID-CT and SARS-CoV-2 datasets, respectively, with a false negative rate which is less than 3% in both datasets. In addition, the Grad-CAM-guided CBIR framework slightly outperforms the plain CBIR in most cases, with respect to nearest neighbour (NN) and first four (FF). The proposed method could serve as a computational tool for a more transparent decision-making process that could be trusted by the medical community. In addition, the employed self-attention mechanism increases the obtained retrieval performance.

Concordance of Bronchoscopic and Radiological Findings in Suspected Lung Cancer and its Outcome- A Cross Sectional Study in a Tertiary Care Hospital

Background: Bronchoscopy and CT thorax are the most common investigations utilized to screen and diagnose lung cancer. Their individual utility in diagnosing lung cancer has been described affirmatively in existing literature. Studies correlating the airway characteristics of the two modalities in lung cancer are limited. Objectives: To analyze and characterize lung lesions bronchoscopically and correlate the same radiologically by CT of the thorax and thus assess its positive predictive value. Methods: In this prospective study, 56 consecutive adults who presented to the Respiratory Medicine Department at a tertiary care hospital in South India from November 2018 to June 2020, having Clinico-radiological suspicion of malignancy and fulfilling study criteria, were recruited. They were subjected to CECT of thorax and bronchoscopy. All bronchoscopic procedures were performed using a protocolized number of passes for biopsy. The baseline demographic and clinical data, findings of bronchoscopy and CT and biopsy reports were recorded. Cohen’s kappa coefficient was used to estimate the agreement of findings on the two modalities. Statistical analysis was performed using SPSS software. Results: Bronchoscopy was normal in 22.14% of cases, the corresponding CTs also revealed normal airway. Bronchoscopy revealed airway lesions in 78.6% of cases; the corresponding CT revealed airway abnormalities in only 46.41% of cases; among these, 52.1% of cases revealed an exophytic growth. There was fair strength of agreement for the two modalities in the detection of airway lesions of lung cancer. (k = 0.38, p = &lt;0.001). CECT thorax has a negative predictive value of 44%, a sensitivity of 59.1% and a specificity of 100% at 95% CI in the detection of airway lesions. Conclusion: CT may not be definitive in the evaluation of lung cancer, especially in those with central disease. A combination of the two modalities may improve the diagnostic outcome in patients with lung cancer.

CRL4B E3 ligase recruited by PRPF19 inhibits SARS-CoV-2 infection by targeting ORF6 for ubiquitin-dependent degradation.

The accessory protein ORF6 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key interferon (IFN) antagonist that strongly suppresses the production of primary IFN as well as the expression of IFN-stimulated genes. However, how host cells respond to ORF6 remains largely unknown. Our research of ORF6-binding proteins by pulldown revealed that E3 ligase components such as Cullin 4B (CUL4B), DDB1, and RBX1 are potential ORF6-interacting proteins. Further study found that the substrate recognition receptor PRPF19 interacts with CUL4B, DDB1, and RBX1 to form a CRL4B-based E3 ligase, which catalyzes ORF6 ubiquitination and subsequent degradation. Overexpression of PRPF19 promotes ORF6 degradation, releasing ORF6-mediated IFN inhibition, which inhibits SARS-CoV-2 replication. Moreover, we found that activation of CUL4B by the neddylation inducer etoposide alleviates lung lesions in a SARS-CoV-2 mouse infection model. Therefore, targeting ORF6 for degradation may be an effective therapeutic strategy against SARS-CoV-2 infection.IMPORTANCEThe cellular biological function of the ubiquitin-proteasome pathway as an important modulator for the regulation of many fundamental cellular processes has been greatly appreciated. The critical role of the ubiquitin-proteasome pathway in viral pathogenesis has become increasingly apparent. It is a powerful tool that host cells use to defend against viral infection. Some cellular proteins can function as restriction factors to limit viral infection by ubiquitin-dependent degradation. In this research, we identificated of CUL4B-DDB1-PRPF19 E3 Ubiquitin Ligase Complex can mediate proteasomal degradation of ORF6, leading to inhibition of viral replication. Moreover, the CUL4B activator etoposide alleviates disease development in a mouse infection model, suggesting that this agent or its derivatives may be used to treat infections caused by SARS-CoV-2. We believe that these results will be extremely useful for the scientific and clinic communities in their search for cues and preventive measures to combat the COVID-19 pandemic.

Clinical application of optical and electromagnetic navigation system in CT-guided radiofrequency ablation of lung metastases

Purpose To evaluate the clinical value of CT-guided radiofrequency ablation (RFA) in the diagnosis and treatment of pulmonary metastases under optical and electromagnetic navigation. Methods Data on CT-guided radiofrequency ablation treatment of 93 metastatic lung lesions in 70 patients were retrospectively analyzed. There were 46 males and 24 females with a median age of 60.0 years (16–85 years). All lesions were ≤3cm in diameter. 57 patients were treated with 17 G radiofrequency ablation needle puncture directly ablated the lesion without biopsy, and 13 patients were treated with 16 G coaxial needle biopsy followed by radiofrequency ablation. There were 25 cases in the optical navigation group, 25 in the electromagnetic navigation group, and 20 in the non-navigation group. The navigation group was performed by primary interventionalists with less than 5 years of experience, and the non-navigation group was performed by interventionalists with more than 5 years of experience. Result All operations were successfully performed. There was no statistically significant difference in the overall distribution of follow-up results among the optical, electromagnetic, and no navigation groups. Complete ablation was achieved in 84 lesions (90.3%). 7 lesions showed incomplete ablation and were completely inactivated after repeat ablation. 2 lesions progressed locally, and one of them still had an increasing trend after repeat ablation. No serious complications occurred after the operation. Conclusions Treatment with optical and electromagnetic navigation systems by less experienced operators has similar outcomes to traditional treatments without navigational systems performed by more experienced operators.

Thoracoscopic versus thoracotomy lobectomy in children with congenital lung lesions: a systematic review and meta-analysis.

Thoracoscopic lobectomy is always compared with open thoracotomy in congenital lung lesions with no definitive results. This systematic review and meta-analysis compared the clinical outcomes of thoracoscopic versus thoracotomy lobectomy in children. The electronic databases MEDLINE, EMBASE, and PubMed were searched. A meta-analysis was used to analyse and compare the operating time, length of hospital stay, and postoperative complications, such as wound infections and respiratory issues, in thoracoscopic and thoracotomy lobectomy. Two thousand and ninety five paediatric patients were analysed over 17 studies (1 ambidirectional cohort study and 16 retrospective studies). Of these patients, 903 and 1192 had undergone thoracoscopic lobectomy and thoracotomy, respectively. There was a significant lower incidence of overall and respiratory complications and longer operative time for thoracoscopic lobectomy compared with thoracotomy in children; however, pooling the results for the two methods revealed no significant difference in wound infection or length of hospital stay. Thoracoscopic lobectomy offers the benefit of having fewer overall and respiratory complications than thoracotomy. It did not, however, clearly outperform open surgery in terms of operative time, wound infection, or postoperative hospitalization.

Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma.

467 Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable HCC, but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. Methods: This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intra-abdomen based on a radiological evaluation adopted from RECIST v 1.1. Up to 2 lesions were chosen as target lesions in each organ for the organ-specific response evaluation. Results: The median age was 60 years. The majority of study patients were male in both groups (83.4% and 85.8% in the atezolizumab-bevacizumab and lenvatinib groups, respectively). The etiology of HCC was similar between the two groups: hepatitis B virus infection was the most common etiology in both groups (73.3% and 65.7% in the atezolizumab-bevacizumab and lenvatinib groups, respectively), while 21.2% and 29.0% of patients had non-viral HCC, respectively. Extrahepatic spread was identified in 76.0% and 74.6% of patients in the atezolizumab-bevacizumab and lenvatinib groups, respectively: lung, LN, and intra-abdominal metastases were present in 39.6% vs. 39.1%, 30.0% vs. 33.1% and 16.6% vs. 15.4% of patients, respectively. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was higher overall in the atezolizumab-bevacizumab group than in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9%, and 33.3% vs. 15.0% for intrahepatic, lung, LN and intra-abdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6% and 36.0% vs. 12.5%, respectively. Among patients with a non-viral etiology, atezolizumab-bevacizumab was not clearly associated with a better organ-specific response for the LN and intra-abdominal lesions: 20.0% vs. 54.5% and 20.0% vs. 25.0%, respectively, for a ≥ 30% reduction in the tumor burden. Conclusions: Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs.

Nintedanib-loaded exosomes from adipose-derived stem cells inhibit pulmonary fibrosis induced by bleomycin.

Pulmonary fibrosis (PF) is a progressive lung disorder with a high mortality rate; its therapy remains limited due to the inefficiency of drug delivery. In this study, the system of drug delivery of nintedanib (Nin) by exosomes derived from adipose-derived stem cells (ADSCs-Exo, Exo) was developed to effectively deliver Nin to lung lesion tissue to ensure enhanced anti-fibrosis therapy. The bleomycin (BLM)-induced PF model was constructed in vivo and in vitro. The effects of Exo-Nin on BLM-induced PF and its regulatory mechanism were examined using RT-qPCR, Western blotting, immunofluorescence, and H&E staining. We found Exo-Nin significantly improved BLM-induced PF in vivo and in vitro compared to Nin and Exo groups alone. Mechanistically, Exo-Nin alleviated fibrogenesis by suppressing endothelial-mesenchymal transition through the down-regulation of the TGF-β/Smad pathway and the attenuation of oxidative stress in vivo and in vitro. Utilizing adipose stem cell-derived exosomes as carriers for Nin exhibited a notable enhancement in therapeutic efficacy. This improvement can be attributed to the regenerative properties of exosomes, indicating promising prospects for adipose-derived exosomes in cell-free therapies for PF. The system of drug delivery of nintedanib (Nin) by exosomes derived from adipose-derived stem cells was developed to effectively deliver Nin to lung lesion tissue to ensure enhanced anti-fibrosis therapy. The use of adipose stem cell-derived exosomes as the carrier of Nin may increase the therapeutic effect of Nin, which can be due to the regenerative properties of the exosomes and indicate promising prospects for adipose-derived exosomes in cell-free therapies for PF.

Multiple Primary Cancers: Association of Breast Cancer and Lung Carcinoma

Multiple primary cancers are relatively rare. The association between lung and breast cancer remains exceptional and requires genetic investigation and identification of factors that promote cancer development. We report the case of a 39-year-old patient who was hospitalized for a left lung lesion with nodules in both breasts. Bronchial biopsies confirmed a primary lung adenocarcinoma. A biopsy of the breast revealed an infiltrating carcinoma of NOS type. The treatment consisted of palliative chemotherapy. Although the association of multiple cancers remains rare, their discovery requires a specific therapeutic approach depending on the staging of each cancer.

Clinical case of treatment of true drowning in fresh water

Drowning is the third leading cause of unintentional injury death worldwide. The largest number of victims of drowning falls on the young able- bodied population.Objective. There are no recent intensive care protocols for drowning, it is relevant to formulate guidelines for the treatment of drowning. Clinical observation. A 25-year-old female patient was taken by an ambulance team to the intensive care unit with a directional diagnosis ‘drowning in fresh water’ of three degree of severity. The patient had got on ventilator with closed aspiration system. Emergency bronchoscopy was performed during which 200 ml of fluid aspirated into the lungs was removed. Respiratory support was determined by stepwise increase of the PEEP level and decrease in FiO2 level taking into account respiratory index. Given the development of a pro-inflammatory mediator response, lactatacidosis, hemolysis, hyperhydration, a high risk of infectious complications, it was decided to start extracorporeal treatment early by continuous veno-venous hemodiafiltration and de-escalation of systemic antibacterial therapy with meropenem by prolonged infusion. Against the background of the ongoing treatment, we managed to achieve target respiratory parameters and stabilize central hemodynamic parameters by the end of the first day, prevent the development of renal damage, correct water-electrolyte and metabolic disorders, and avoid severe septic complications. Vasopressor support was discontinued on the 4th day, and on the 5th day the patient was switched to independent breathing. The patient`s stay in the intensive care unit was 6 days.Conclusions. Stepwise respiratory therapy using closed suction systems and urgent bronchoscopy prevent direct damage to the alveoli and ongoing translocation of fluid into the vascular bed. Prescribing broad-spectrum antibiotics prior to the growth of clinical and laboratory signs of infectious lung lesions allows to reduce the risk of severe septic complications with pulmonary destruction parenchyma. Early onset extracorporeal treatment by CVVHDF allows to correct homeostasis disorders, eliminate hypervolemia, prevent the development of acute renal damage as a result of hemolysis.

Club cell-specific telomere protection protein 1 (TPP1) protects against tobacco smoke-induced lung inflammation, xenobiotic metabolic dysregulation, and injurious responses.

Inhaling xenobiotics, such as tobacco smoke is a major risk factor for pulmonary diseases, e.g., COPD/emphysema, interstitial lung disease, and pre-invasive diseases. Shelterin complex or telosome provides telomeric end protection during replication. Telomere protection protein 1 (TPP1) is one of the main six subunits of the shelterin complex supporting the telomere stability and genomic integrity. Dysfunctional telomeres and shelterin complex are associated as a disease mechanism of tobacco smoke-induced pulmonary damage and disease processes. The airway epithelium is critical to maintaining respiratory homeostasis and is implicated in lung diseases. Club cells (also known as clara cells) play an essential role in the immune response, surfactant production, and metabolism. Disrupted shelterin complex may lead to dysregulated cellular function, DNA damage, and disease progression. However, it is unknown if the conditional removal of TPP1 from Club cells can induce lung disease pathogenesis caused by tobacco smoke exposure. In this study, conditional knockout of Club-cell specific TPP1 demonstrated the instability of other shelterin protein subunits, such as TRF1, dysregulation of cell cycle checkpoint proteins, p53 and downstream targets, and dysregulation of telomeric genes. This was associated with age-dependent senescence-associated genes, increased DNA damage, and upregulated RANTES/IL13/IL33 mediated lung inflammation and injury network by cigarette smoke (CS). These phenomena are also associated with alterations in cytochrome P450 and glutathione transferases, upregulated molecular pathways promoting lung lesions, bronchial neoplasms, and adenocarcinomas. These findings suggest a pivotal role of TPP1 in maintaining lung homeostasis and injurious responses in response to CS. Thus, these data TPP1 may have therapeutic value in alleviating telomere-related chronic lung diseases.

A Mixture of T-Cell Epitope Peptides Derived from Human Respiratory Syncytial Virus F Protein Conferred Protection in DR1-TCR Tg Mice.

Human respiratory syncytial virus (HRSV) poses a significant disease burden on global health. To date, two vaccines that primarily induce humoral immunity to prevent HRSV infection have been approved, whereas vaccines that primarily induce T-cell immunity have not yet been well-represented. To address this gap, 25 predicted T-cell epitope peptides derived from the HRSV fusion protein with high human leukocyte antigen (HLA) binding potential were synthesized, and their ability to be recognized by PBMC from previously infected HRSV cases was assessed using an ELISpot assay. Finally, nine T-cell epitope peptides were selected, each of which was recognized by at least 20% of different donors' PBMC as potential vaccine candidates to prevent HRSV infection. The protective efficacy of F-9PV, a combination of nine peptides along with CpG-ODN and aluminum phosphate (Al) adjuvants, was validated in both HLA-humanized mice (DR1-TCR transgenic mice, Tg mice) and wild-type (WT) mice. The results show that F-9PV significantly enhanced protection against viral challenge as evidenced by reductions in viral load and pathological lesions in mice lungs. In addition, F-9PV elicits robust Th1-biased response, thereby mitigating the potential safety risk of Th2-induced respiratory disease during HRSV infection. Compared to WT mice, the F-9PV mice exhibited superior protection and immunogenicity in Tg mice, underscoring the specificity for human HLA. Overall, our results demonstrate that T-cell epitope peptides provide protection against HRSV infection in animal models even in the absence of neutralizing antibodies, indicating the feasibility of developing an HRSV T-cell epitope peptide-based vaccine.

Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma.

Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable hepatocellular carcinoma (HCC), but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. We aimed to investigate the organ-specific response patterns among unresectable HCC patients treated with first-line atezolizumab-bevacizumab or lenvatinib. This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intraabdomen based on a radiological evaluation adopted from RECIST v 1.1. The median age was 60years. Hepatitis B infection was the most common etiology (n = 270, 69.9%), and 291 (75.4%) patients had a viral etiology. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was overall higher in the atezolizumab-bevacizumab group than that in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9% and 33.3% vs. 15.0% for intrahepatic, lung, LN, and intraabdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6%, and 36.0% vs. 12.5%, respectively. Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs.

Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.

Brain metastases stemming from lung cancer represent a common and challenging complication that significantly impacts patients' overall health. The migration of these cancerous cells from lung lesions to the central nervous system is facilitated by diverse molecular changes and a specific environment that supports their affinity for neural tissues. The advent of immunotherapy and its varied combinations in non-small cell lung cancer has notably improved patient survival rates, even in cases involving brain metastases. These therapies exhibit enhanced penetration into the central nervous system compared to traditional chemotherapy. This review outlines the molecular mechanisms underlying the development of brain metastases in lung cancer and explores the efficacy of novel immunotherapy approaches and their combinations.

Clinical case of Loeffler’s endomyocarditis

Eosinophilic endomyocarditis is caused by direct infiltration of heart tissue by eosinophils with the development of specific inflammation. The main etiological factor of the disease is a significant increase in the level of eosinophils in peripheral blood. Loeffler syndrome can be caused by such factors and pathological conditions as idiopathic hypereosinophilic syndrome, allergic diseases, parasitic infections, autoimmune processes, cancer. A clinical case of Loeffler syndrome in an 84-year-old patient with heart, lung, liver, kidney and pancreatic lesions is presented. Difficulties of differential diagnostics of this syndrome because of individual clinical picture and signs of the course are discussed in the article. Timely diagnosis of such a condition will prevent the rapid development of severe complications and carry out appropriate therapy, which will significantly prolong the life of patients with Loeffler syndrome. However, in the presence of nonspecific symptoms, the diagnosis of this disease may be diagnostically difficult for the physician.

Different populations of A(H1N1)pdm09 viruses in a patient with hemolytic-uremic syndrome

Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized.A patient (age group 5–15 years) displaying symptoms of hemolytic uremic syndrome died one day after hospitalization. qPCR, next generation sequencing, virus isolation, antigenic characterization, resistance analysis was performed and virus replication kinetics in well-differentiated airway cells were determined.Autopsy revealed hemorrhagic pneumonia as major pathological manifestation. Lung samples harbored a large population of A(H1N1)pdm09 viruses with the polymorphism H456H/Y in PB1 polymerase. The H456H/Y viruses replicated much faster to high viral titers than upper respiratory tract viruses in vitro. H456H/Y-infected air-liquid interface cultures of differentiated airway epithelial cells did reflect a more pronounced loss of ciliated cells. A different pattern of virus quasispecies was found in the upper airway samples where substitution S263S/F (HA1) was observed.The data support the notion that viral quasispecies had evolved locally in the lung to support high replicative fitness. This change may have initiated further pathogenic processes leading to rapid dissemination of inflammatory mediators followed by development of hemorrhagic lung lesions and fatal outcome.