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Interdisciplinary Cardiovascular and... Jun 2024Postoperative air leakage is a major complication of lung resection, particularly right upper lobectomy. However, various surgical procedures can reduce postoperative...
OBJECTIVES
Postoperative air leakage is a major complication of lung resection, particularly right upper lobectomy. However, various surgical procedures can reduce postoperative complications and shorten the drainage period. The current study aimed to analyze the utility of bronchus-first right upper lobectomy as an alternative routine procedure.
METHODS
We retrospectively analyzed the data of 225 (53.7%) patients who underwent bronchus-first right upper lobectomy and 194 (46.3%) patients who underwent the conventional bronchus-last right upper lobectomy at our institution from 2015 to 2022. In patients with incomplete fissures who underwent bronchus-first right upper lobectomy, the bronchus was dissected firstly, followed by the pulmonary artery and vein, then, the interlobar fissure was divided. We compared the outcomes of two procedures and analyzed the surgical utility of bronchus-first right upper lobectomy.
RESULTS
The surgical outcomes and postoperative morbidity comparing bronchus-first and bronchus-last procedure were as followed: median operation time (min) 103/126 (p < 0.001), median bleeding amount (mL) 28/55 (p = 0.003), incomplete lobulation rate (%) 35.1/24.2 (p = 0.02), incidence of prolonged air leakage (%) 2.2/3.1 (p = 0.76) and rate of fellow surgeon's operation (%) 28.0/4.6 (p < 0.001). The procedure was associated with a decreased incidence of prolonged air leakage. The 4-year overall survival rates did not significantly differ between the two groups (p = 0.24).
CONCLUSIONS
Bronchus-first right upper lobectomy can prevent postoperative air leakage in patients with incomplete fissure. Additionally, as an alternative routine procedure, it is associated with a shorter surgical duration and a lower volume of blood loss regardless of interlobar fissure and operator's experience.
PubMed: 38913868
DOI: 10.1093/icvts/ivae114 -
PloS One 2024The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This...
The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.
Topics: Animals; Asthma; Rosuvastatin Calcium; AMP-Activated Protein Kinases; Signal Transduction; Airway Remodeling; Mice; Disease Models, Animal; Ovalbumin; Female; Mice, Inbred BALB C; Bronchoalveolar Lavage Fluid; Chronic Disease; Inflammation; Lung; Immunoglobulin E
PubMed: 38913666
DOI: 10.1371/journal.pone.0305863 -
JCI Insight May 2024Immune therapy is the new frontier of cancer treatment. Therapeutic radiation is a known inducer of immune response and can be limited by immunosuppressive mediators...
Immune therapy is the new frontier of cancer treatment. Therapeutic radiation is a known inducer of immune response and can be limited by immunosuppressive mediators including cyclooxygenase-2 (COX2) that is highly expressed in aggressive triple negative breast cancer (TNBC). A clinical cohort of TNBC tumors revealed poor radiation therapeutic efficacy in tumors expressing high COX2. Herein, we show that radiation combined with adjuvant NSAID (indomethacin) treatment provides a powerful combination to reduce both primary tumor growth and lung metastasis in aggressive 4T1 TNBC tumors, which occurs in part through increased antitumor immune response. Spatial immunological changes including augmented lymphoid infiltration into the tumor epithelium and locally increased cGAS/STING1 and type I IFN gene expression were observed in radiation-indomethacin-treated 4T1 tumors. Thus, radiation and adjuvant NSAID treatment shifts "immune desert phenotypes" toward antitumor M1/TH1 immune mediators in these immunologically challenging tumors. Importantly, radiation-indomethacin combination treatment improved local control of the primary lesion, reduced metastatic burden, and increased median survival when compared with radiation treatment alone. These results show that clinically available NSAIDs can improve radiation therapeutic efficacy through increased antitumor immune response and augmented local generation of cGAS/STING1 and type I IFNs.
Topics: Animals; Membrane Proteins; Mice; Female; Signal Transduction; T-Lymphocytes, Cytotoxic; Triple Negative Breast Neoplasms; Indomethacin; Cell Line, Tumor; Humans; Lung Neoplasms; Cyclooxygenase Inhibitors; Nucleotidyltransferases; Interferon Type I; Cyclooxygenase 2; Lymphocytes, Tumor-Infiltrating; Mice, Inbred BALB C
PubMed: 38912586
DOI: 10.1172/jci.insight.165356 -
Heliyon Jun 2024Inferior vena cava filters have been shown to be effective in preventing deep vein thrombosis and its secondary complication, pulmonary embolism, thereby reducing the...
BACKGROUND AND OBJECTIVE
Inferior vena cava filters have been shown to be effective in preventing deep vein thrombosis and its secondary complication, pulmonary embolism, thereby reducing the high mortality rate. Although inferior vena cava filters have evolved, specific complications like inferior vena cava thrombosis-induced deep vein thrombosis worsening and recurrent pulmonary embolism continue to pose challenges. This study analyzes the effects of geometric parameter variations of inferior vena cava filters, which have a significant impact on the thrombus formation inside the filter, the capture, dissolution, and hemodynamic flow of thrombus, as well as the shear stress on the filter and vascular wall.
METHODS
This study used computational fluid dynamic simulations with the carreau model to investigate the impact of varying inferior vena cava filter design parameters (number of struts, strut arm length, and tilt angle) on hemodynamics.
RESULTS
Recirculation and stagnation areas due to flow velocity and pressure, along with wall shear stress values, were identified as key factors. It is important to find a balance between wall shear stress high enough to aid thrombolysis and low enough to prevent platelet activation. The results of this paper show that the risk of platelet activation and thrombus filtration may be lowest when the wall shear stress of the filter ranges from 0 to 4 [Pa], minimizing stress concentration within the filter.
CONCLUSION
16 arm struts with a length of 20 mm and a tilt angle of 0° provide the best balance between thrombus capture and minimization of hemodynamic disturbance. This configuration minimizes the size of the stagnation and recirculation zones while maintaining sufficient wall shear stress for thrombus dissolution.
PubMed: 38912484
DOI: 10.1016/j.heliyon.2024.e32667 -
Journal of Inflammation Research 2024Dermatomyositis (DM) represents a group of inflammatory myopathies, with TIF1-γ positive DM strongly associated with malignancies. Spontaneous muscular hematoma in DM...
BACKGROUND
Dermatomyositis (DM) represents a group of inflammatory myopathies, with TIF1-γ positive DM strongly associated with malignancies. Spontaneous muscular hematoma in DM patients is exceedingly rare and often prognosticates a severe clinical outcome, especially in the context of concurrent malignancy.
CASE PRESENTATION
We describe a novel survival case of a patient with TIF1-γ positive DM and an underlying ovarian tumor who developed a spontaneous muscular hematoma. Despite the traditionally poor prognosis of these conditions, the patient survived through a comprehensive treatment regimen. This included targeted chemotherapy for ovarian cancer (Carboplatin and Paclitaxel), alongside corticosteroids, immunoglobulins, and immunosuppressants for DM, as well as component blood transfusions, coagulation correction therapy to control hematoma, and integrated management: nutritional support, lung function exercise, volume management.
RESULTS
The integrated treatment strategy stabilized the patient's condition and resolved the hematoma, a significant achievement given the usual high mortality rate of such complications.
CONCLUSION
This case underscores the importance of a multidisciplinary approach in the early diagnosis and treatment of TIF1-γ positive DM with complex comorbidities, including spontaneous muscular hematoma and ovarian cancer. It highlights the potential for favorable outcomes with aggressive and coordinated treatment strategies.
PubMed: 38911988
DOI: 10.2147/JIR.S469401 -
Frontiers in Immunology 2024Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are...
Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium is located next to infected epithelial cells and bystander inflammation may contribute to thromboinflammation and COVID-19-associated coagulopathy. Here, we investigated age-associated SARS-CoV-2 pathogenesis and endothelial inflammatory responses using humanized K18-hACE2 mice. Survival was reduced to 20% in aged mice (85-112 weeks) versus 50% in young mice (12-15 weeks) at 10 days post infection (dpi). Bulk RNA-sequencing of endothelial cells from mock and infected mice at 2dpi of both age groups (aged: 72-85 weeks; young: 15 weeks) showed substantially lower significant differentially regulated genes in infected aged mice than in young mice (712 versus 2294 genes). Viral recognition and anti-viral pathways such as RIG-I-like receptor signaling, NOD-like receptor signaling and interferon signaling were regulated in response to SARS-CoV-2. Young mice showed several fold higher interferon responses (, , ) and interferon-induced chemokines ( and ) than aged mice. Endothelial cells from infected young mice displayed elevated expression of chemokines (, ) and leukocyte adhesion markers () underscoring that inflammation of lung endothelium during infection could facilitate leukocyte adhesion and thromboinflammation. TREM1 and acute phase response signaling were particularly prominent in endothelial cells from infected young mice. Immunohistochemistry was unable to detect viral protein in pulmonary endothelium. In conclusion, our data demonstrate that the early host response of the endothelium to SARS-CoV-2 infection declines with aging, which could be a potential contributor to disease severity.
Topics: Animals; COVID-19; SARS-CoV-2; Endothelial Cells; Mice; Lung; Humans; Aging; Disease Models, Animal; Inflammation; Angiotensin-Converting Enzyme 2; Mice, Transgenic
PubMed: 38911865
DOI: 10.3389/fimmu.2024.1397990 -
Frontiers in Immunology 2024Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy....
BACKGROUND
Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy.
METHODS
Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy.
RESULTS
Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20-2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P<.0001, HR 0.33, 95% CI: 0.20-0.55) and the metastatic cohort (P<.0001, HR 0.28, 95% CI: 0.15-0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P<.0001).
CONCLUSION
Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy.
Topics: Humans; Small Cell Lung Carcinoma; Neutrophils; Male; Female; Immune Checkpoint Inhibitors; Lung Neoplasms; Aged; Middle Aged; Lymphocytes; Biomarkers, Tumor; Prognosis; Serum Albumin, Human; Serum Albumin; Aged, 80 and over; Retrospective Studies; Adult; Lymphocyte Count
PubMed: 38911864
DOI: 10.3389/fimmu.2024.1327449 -
Frontiers in Aging 2024Older adults with chronic disease prioritize functional independence. We aimed to describe the feasibility of capturing functional disability and treatment toxicity...
INTRODUCTION
Older adults with chronic disease prioritize functional independence. We aimed to describe the feasibility of capturing functional disability and treatment toxicity among older adults with lung cancer using a longitudinal comprehensive geriatric assessment (CGA) and molecular biomarkers of aging.
METHODS
This prospective study included adults ≥60 years with any newly diagnosed non-small-cell lung cancer. Participants were recruited from central Ohio (2018-2020). Study assessments included the Cancer and Aging Research Group CGA (CARG-CGA), short physical performance battery (SPPB), and the blessed orientation-memory concentration (BOMC) test at baseline, 3, 6, and 12 months. Activities of daily living (ADLs) and instrumental ADLs (IADLs), quality of life (QoL, PROMIS 10), and treatment toxicity were captured monthly. Stool and blood were collected to characterize the gut microbiome and age-related blood biomarkers.
RESULTS
This study enrolled 50 participants with an average age of 71.7 years. Ninety-two percent of participants were Caucasian, 58% were male, and all were non-Hispanic. Most had advanced stage (stage III/IV: 90%; stage I/II: 10%), with adenocarcinoma the predominant histologic subtype (68% vs. 24% squamous). First-line treatments included chemotherapy (44%), immune checkpoint inhibitors (ICIs, 22%), chemotherapy and ICIs (30%), or tyrosine kinase inhibitors (4%). The median baseline CARG toxicity score was 8 (range 2-12). Among patients with treatment-related toxicity ( = 49), 39 (79.6%) cases were mild (grade 1-2), and 10 (20.4%) were moderate to severe (≥ grade 3). Treatment toxicity was greater among those with a CARG score ≥8 (28.0% vs. 13.6%). Higher IADL independence, QoL, and SPPB scores at baseline were positively associated with , , and , , and and T cell and were associated with worse IADLs, QoL, and SPPB scores at baseline.
DISCUSSION
A longitudinal CGA and biomarker collection is feasible among older adults undergoing lung cancer treatment. Gut microbe and T cell gene expression changes correlated with subjective and objective functional status assessments. Future research will test causality in these associations to improve outcomes through novel supportive care interventions to prevent functional disability.
PubMed: 38911592
DOI: 10.3389/fragi.2024.1268232 -
Frontiers in Pediatrics 2024Traffic accidents, particularly blunt impacts, cause serious injuries in children. We aimed to assess inflammatory and injury responses in infant rabbits subjected to...
BACKGROUND
Traffic accidents, particularly blunt impacts, cause serious injuries in children. We aimed to assess inflammatory and injury responses in infant rabbits subjected to acute lung injury resulting from blunt impact, with the goal of identifying potential circulatory injury markers.
METHODS
Forty 4-week-old infant rabbits were subjected to a right chest impact using a Hopkinson bar with 2,600 g. Computed tomography was employed to assess injury severity. Pathological changes were observed using hematoxylin and eosin staining in the control, 0, 24, and 72 h groups, post-injury. Immunohistochemistry was used to examine surfactant protein A (SP-A) changes in right lung tissues and upper main bronchi. Serum levels of interleukin-6 (IL-6), IL-8, and SP-A were measured using ELISA within 24 h post-injury in the control, 0 h, and 24 h groups.
RESULTS
Following blunt injury, significant increases were observed in blood white blood cell count ( = 101.556, < 0.01) and neutrophil percentage ( = 104.228, < 0.01), which gradually decreased after 24 and 72 h. The lung wet/dry weight ratio indicated significant edema ( = 79.677, < 0.01), corroborated by hematoxylin and eosin staining showing edema, exudation, and marked granulocyte infiltration in the control, 0 h, 24 h and 72 h groups. SP-A levels decreased rapidly at 0 h, and recovered between 24 and 72 h in the right lung tissues ( = 6.7, < 0.05), left lung ( = 15.825, < 0.05) and upper main bronchi ( = 59.552, < 0.01). The ELISA results showed increasing trends for the control and 0 h groups, while decreasing trends were observed in 24 h group for IL-6 ( = 58.328, < 0.01) and IL-8 ( = 41.802, < 0.01). Conversely, SP-A exhibited a decreasing trend in the control and 0 h groups but increased in the serum of 24 h group ( = 52.629, < 0.01).
DISCUSSION
In cases of direct chest trauma in infant rabbits, particularly mild injuries without rib fractures. SP-A levels correlated with pathological changes across all groups and may serve as biomarkers for pediatric blunt lung impact.
PubMed: 38910959
DOI: 10.3389/fped.2024.1354531 -
Allergy, Asthma & Immunology Research May 2024Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the...
PURPOSE
Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice.
METHODS
This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized.
RESULTS
With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported.
CONCLUSIONS
Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.
PubMed: 38910283
DOI: 10.4168/aair.2024.16.3.253