Abemaciclib-induced lung damage leading to discontinuation in brain metastases from breast cancer: A case report

BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estrogen receptor-positive,HER2-negative breast cancer who developed brain metastasis.The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discon-tinuation due to drug-induced lung damage(DILD).CASE SUMMARY In this comprehensive case summary,we present the clinical course of a woman in her 60s,who 11 years following primary breast cancer surgery,was diagnosed with multiple brain metastases.As a third-line systemic therapy,she underwent treatment with abemaciclib and letrozole.This treatment approach yielded a near-partial response in her metastatic brain lesions.However,abemaciclib adminis-tration ceased due to the emergence of DILD,as confirmed by a computed tomography scan.The DILD improved after 1 mo of cessation.Despite ongoing therapeutic efforts,the patient’s condition progressively deteriorated,ultimately resulting in death due to progression of the brain metastases.CONCLUSION This case underscores the challenge of managing adverse events in responsive brain metastasis patients,given the scarcity of therapeutic options.

Perspectives on mesenchymal stem/progenitor cells and their derivates as potential therapies for lung damage caused by COVID-19

The new coronavirus,severe acute respiratory syndrome coronavirus-2(SARSCoV-2),which emerged in December 2019 in Wuhan,China,has reached worldwide pandemic proportions,causing coronavirus disease 2019(COVID-19).The clinical manifestations of COVID-19 vary from an asymptomatic disease course to clinical symptoms of acute respiratory distress syndrome and severe pneumonia.The lungs are the primary organ affected by SARS-CoV-2,with a very slow turnover for renewal.SARS-CoV-2 enters the lungs via angiotensinconverting enzyme 2 receptors and induces an immune response with the accumulation of immunocompetent cells,causing a cytokine storm,which leads to target organ injury and subsequent dysfunction.To date,there is no effective antiviral therapy for COVID-19 patients,and therapeutic strategies are based on experience treating previously recognized coronaviruses.In search of new treatment modalities of COVID-19,cell-based therapy with mesenchymal stem cells(MSCs)and/or their secretome,such as soluble bioactive factors and extracellular vesicles,is considered supportive therapy for critically ill patients.Multipotent MSCs are able to differentiate into different types of cells of mesenchymal origin,including alveolar epithelial cells,lung epithelial cells,and vascular endothelial cells,which are severely damaged in the course of COVID-19 disease.Moreover,MSCs secrete a variety of bioactive factors that can be applied for respiratory tract regeneration in COVID-19 patients thanks to their trophic,anti-inflammatory,immunomodulatory,anti-apoptotic,pro-regenerative,and proangiogenic properties.

Oleuropein alleviates sepsis-induced acute lung injury via the AMPK/Nrf-2/HO-1 signaling

Objective:To explore the effect of oleuropein on sepsis-induced acute lung injury(ALI)in vitro and in vivo and investigate the underlying mechanism.Methods:In an lipopolysaccharide(LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI,CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis.ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress,respectively.Western blot was applied to determine the expression of apoptosis-and AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor-2(Nrf-2)/heme oxygenase-1(HO-1)signaling-associated proteins.JC-1 staining,adenosine triphosphate(ATP)assay kit,and MitoSOX Red assays were performed to detect mitochondrial membrane potential,ATP content,and mitochondrial ROS formation,respectively.Moreover,lung injury was evaluated by measuring lung morphological alternations,lung wet-to-dry ratio,myeloperoxidase content,and total protein concentration.Results:Oleuropein reduced inflammatory reaction,oxidative damage,and apoptosis,and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI.Besides,oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway.However,these effects of oleuropein were abrogated by an AMPK inhibitor compound C.Conclusions:Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling,which might be a potential therapeutic agent for the treatment of sepsis-induced ALI.

Discussion on the Prevention and Treatment of COVID-19 Causing Lung Disease and Heart Damage Based on Lei Zhongyi's Theory of Intermingled Phlegm,Blood Stasis and Toxin

Novel coronavirus infection not only damages lung function,but also causes myocardial injury,elevated myocardial enzymes and heart failure,especially for patients with basic heart diseases who develop COVID-19,the first consideration should be the protection of cardiac function.Based on the theory of intermingled phlegm,blood stasis and toxin of heart disease put forward by Master Lei Zhongyi,the dialectical treatment thinking of COVID-19 patients from the concept of damage of phlegm,blood stasis and toxin to the heart were discussed.During the diagnosis,critical stage and recovery period of COVID-19,expectorant and blood-activating agents,heat and detoxification agents can be added to promote lung and asthma,free Bizheng and remove blood stasis,calm the heart and calm the mind,and promote the recovery of cardiopulmonary functions.

Review on radiological evolution of COVID-19 pneumonia using computed tomography

BACKGROUND Pneumonia is the main manifestation of coronavirus disease 2019(COVID-19)infection.Chest computed tomography is recommended for the initial evaluation of the disease;this technique can also be helpful to monitor the disease progression and evaluate the therapeutic efficacy.AIM To review the currently available literature regarding the radiological follow-up of COVID-19-related lung alterations using the computed tomography scan,to describe the evidence about the dynamic evolution of COVID-19 pneumonia and verify the potential usefulness of the radiological follow-up.METHODS We used pertinent keywords on PubMed to select relevant studies;the articles we considered were published until October 30,2020.Through this selection,69 studies were identified,and 16 were finally included in the review.RESULTS Summarizing the included works’findings,we identified well-defined stages in the short follow-up time frame.A radiographic deterioration reaching a peak roughly within the first 2 wk;after the peak,an absorption process and repairing signs are observed.At later radiological follow-up,with the limitation of little evidence available,the lesions usually did not recover completely.CONCLUSION Following computed tomography scan evolution over time could help physicians better understand the clinical impact of COVID-19 pneumonia and manage the possible sequelae;a longer follow-up is advisable to verify the complete resolution or the presence of long-term damage.

Effect of oxidative stress-associated damage to the lung tissue caused by different body mass index in the rat models

Objective To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal(4-HNE),thioredoxin(Trx),thioredoxin reductase(TrxR)and the sctivities of Trx and TrxR,and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models.Methods