Hemorrhagic fever with renal syndrome complicated with aortic dissection:A case report

BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection.Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically.Here,we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection.CASE SUMMARY A 56-year-old man complained of high fever and generalized body ache,with decreased platelet counts of 10×10^9/L and acute kidney injury.The enzymelinked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive.During the convalescent period,he complained sudden onset acute chest pain radiating to the back,and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery.He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection.The patient recovered completely after surgery with other support treatments.CONCLUSION Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition.Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment.A causal relationship has yet to be confirmed.

Eye metastasis in lung adenocarcinoma mimicking anterior scleritis:A case report

BACKGROUND The eye is a rare site for lung cancer metastasis. Indeed, ocular metastasis is one of the greatest challenges to quality of life in a cancer patient. Here we present a patient with lung adenocarcinoma and ocular metastasis.CASE SUMMARY The patient was a 70-year-old man diagnosed with lung adenocarcinoma who developed eye metastasis mimicking anterior scleritis. Brain magnetic resonance imaging showed an abnormal signal in the right eye. Based on next generation sequencing of the surgical specimen, the patient was shown to have a KRAS point mutation(p.G12D).CONCLUSION Multidiscipline expertise collaboration is needed to make the early diagnosis and determine the prompt treatment in patients. We hope to increase the awareness of the possibility of lung cancer metastasizing to the eye.

Treatment failure in a patient infected with Listeria sepsis combined with latent meningitis:A case report

BACKGROUND Listeria is a food-borne disease,which is rarely prevalent in the normal population;it mostly occurs in pregnant women,newborns,immunodeficiency patients,and the elderly.The main manifestations of this disease in patients include sepsis,meningitis,etc,and the mortality rate remains high,although the onset of meningitis is relatively insidious.CASE SUMMARY A 75-year-old man presented with a fever for 1 wk and was admitted to the hospital for diagnosis and management of a lung infection.His condition improved after receiving anti-infective treatment for 2 wk.However,soon after he was discharged from the hospital,he developed fever again,and gradually developed various neurological symptoms,impaired consciousness,and stiff neck.Thereafter,through the cerebrospinal fluid metagenomic testing and blood culture,the patient was diagnosed with Listeria monocytogenes meningitis and sepsis.The patient died after being given active treatment,which included penicillin application and invasive respiratory support.CONCLUSION This case highlights the ultimate importance of early identification and timely application of the various sensitive antibiotics,such as penicillin,vancomycin,meropenem,etc.Therefore,for high-risk populations with unknown causes of fever,multiple blood cultures,timely cerebrospinal fluid examination,and metagenomic detection technology can assist in confirming the diagnosis quickly,thereby guiding the proper application of antibiotics and improving the prognosis.

Josephin domain containing 2(JOSD2)promotes lung cancer by inhibiting LKB1(Liver kinase B1)activity

Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC patients.Consequently,the need for novel strategies addressing NSCLC remains pressing.Deubiquitinases(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets.Nevertheless,the mechanisms by which DUBs promote NSCLC remain poorly understood.Through a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of patients.Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo.Mechanically,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex.Notably,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo.Our findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.

Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study

Background:The initial phase II stuty(NCT03215693)demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory,anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC).Herein,we reported the updated data on overall survival(OS)and molecular profiling from the initial phase Ⅱ study.Methods:In this study,180 patients received 225 mg of ensartinib orally once daily until disease progression,death or withdrawal.OS was estimated by Kaplan‒Meier methods with two-sided 95%confidence intervals(CIs).Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib.Circulating tumor DNA(ctDNA)was detected to dynamically monitor the genomic alterna-tions during treatment and indicate the existence of molecular residual disease,facilitating improvement of clinical management.Results:At the data cut-off date(August 31,2022),with a median follow-up time of 53.2 months,97 of 180(53.9%)patients had died.The median OS was 42.8 months(95%CI:29.3-53.2 months).A total of 333 plasma samples from 168 patients were included for ctDNA analysis.An inferior OS correlated sig-nificantly with baseline ALK or tumor protein 53(TP53)mutation.In addition,patients with concurrent TP53 mutations had shorter OS than those without con-current TP53 mutations.High ctDNA levels evaluated by variant allele frequency(VAF)and haploid genome equivalents per milliliter of plasma(hGE/mL)at baseline were associated with poor OS.Additionally,patients with ctDNA clear-ance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth,respectively.Furthermore,patients who had a lower tumor burden,as evaluated by the diameter of target lesions,had a longer OS.Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases,higher hGE,and elevated ALK mutation abundance at 6 weeks.Conclusion:Ensartinib led to a favorable OS in patients with advanced,crizotinib-resistant,and ALK-positive NSCLC.Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Tumor organoids:synergistic applications,current challenges,and future prospects in cancer therapy

Patient-derived cancer cells(PDCs)and patient-derived xenografts(PDXs)are often used as tumor models,but have many shortcomings.PDCs not only lack diversity in terms of cell type,spatial organization,and microenvironment but also have adverse effects in stem cell cultures,whereas PDX are expensive with a low transplantation success rate and require a long culture time.In recent years,advances in three-dimensional(3D)organoid culture technology have led to the development of novel physiological systems that model the tissues of origin more precisely than traditional culture methods.Patient-derived cancer organoids bridge the conventional gaps in PDC and PDX models and closely reflect the pathophysiological features of natural tumorigenesis and metastasis,and have led to new patient-specific drug screening techniques,development of individualized treatment regimens,and discovery of prognostic biomarkers and mechanisms of resistance.Synergistic combinations of cancer organoids with other technologies,for example,organ-on-a-chip,3D bio-printing,and CRISPR-Cas9-mediated homology-independent organoid transgenesis,and with treatments, such as immunotherapy, have been useful in overcoming their limitations and led to the development of more suitable model systems that recapitulate the complex stroma of cancer, inter-organ and intra-organ communications,and potentially multiorgan metastasis. In this review, we discuss various methods for the creation of organ-specific cancer organoids and summarize organspecific advances and applications, synergistic technologies, and treatments aswell as current limitations and future prospects for cancer organoids. Furtheradvances will bring this novel 3D organoid culture technique closer to clinicalpractice in the future.

Neoadjuvant ceritinib treatment achieved pathological complete response in patients with anaplastic lymphoma kinase positive stage IIIA-N2 non-small cell lung cancer

To the Editor:Anaplastic lymphoma kinase(ALK)fusion oncogene occurs in 3%to 7%of patients with non-small cell lung cancer(NSCLC),with the most common companion being echinoderm microtubule-associated protein-like 4.

Syndecan 4-c-ros oncogene 1 fusion as a mechanism of acquired resistance in epidermal growth factor receptor mutant lung adenocarcinoma

To the Editor:A 37-year-old Chinese woman,a nonsmoker,presented with adenocarcinoma of the left lung(stage IV)[Figure 1A],malignant pleural effusion,and multiple bone metastases in December 2014.Deoxyribonucleic acid sequencing of the tumor biopsy revealed an epidermal growth factor receptor(EGFR)exon 19 deletion,and treatment with gefitinib was consequently initiated in December 2014.There were no treatmentrelated side effects except for a grade 1 rash,and stable disease was achieved.Unfortunately,the patient did not experience long-term benefits and developed disease progression after only two months.A follow-up examination showed that extracranial disease and a small intracranial lesion had developed gradually.The patient then received whole-brain radiotherapy(30 Gy in ten fractions)and four cycles of single-agent pemetrexed in April 2015.Stable disease was achieved,which coincided with an improvement in the patient’s cough,shortness of breath,and general condition.The chemotherapy course was changed to two cycles of pemetrexed combined with cisplatin.A partial response(PR)was achieved,and the patient was treated with 14 cycles of pemetrexed alone as maintenance chemotherapy.The follow-up evaluations showed the patient’s condition to be stable;however,the patient’s disease progressed after 23 months.A computed tomography(CT)scan in March 2017 revealed that both the lung lesion and the malignant pleural effusion had increased in size[Figure 1B].The subsequent biopsy specimen was subjected to next-generation sequencing(NGS)and a Syndecan 4-c-ros oncogene 1(SDC4-ROS1)rearrangement was detected[Figure 1C].The patient then received crizotinib in April 2017,and a PR was achieved[Figure 1D].A CT scan done in August 2018 indicated the progression of the primary lesion in the left lung and malignant pleural effusion.However,the growth of the remaining lesions remained stable.