Fetal Lung Cells Transfer Improves Emphysematous Change in a Mouse Model of Neutrophil Elastase-Induced Lung Emphysema.

Recently, several studies for lung regeneration have been reported. However, regenerating the lung tissue by the transfer of any cells directly to the lung has been hardly successful. The aim of this study was to evaluate the effect of fetal lung cells (FLCs) in a mouse model of lung emphysema. C57BL/6 mice were stimulated with neutrophil elastase (NE) intra-tracheally (i.t.) to generate lung emphysema. To collect fetal lung cells, C57BL/6-Tg (CAG-EGFP) mice were bred for 14 days. Before delivery, the bred mice were euthanized, and fetal lungs were harvested from the fetal mice and the cells were collected. The FLCs were transferred i.t. 24 h after the NE instillation. Four weeks after the NE instillation, mice were euthanized, and the samples were collected. The mean linear intercept (MLI) was significantly prolonged in the NE instillation group compared to the control group. However, in the FLCs transfer group stimulated with NE, the MLI became shorter than the NE-stimulated group without an FLCs transfer. This result shows that an FLCs transfer inhibited the progression of lung emphysema. Additionally, motility of the mice was also improved by the FLCs transfer. These results indicate that transfer of the FLCs, which were presumed to be progenitor cells for lung tissue, may improve the emphysematous change.

Multiple cerebral syphilitic gummas mimicking brain tumor in a non-HIV-infected patient: A case report.

We present a unique case of symptomatic early neurosyphilis in a non-HIV-infected patient. A 47-year-old man with a history of diabetes mellitus presented with generalized seizures. He did not manifest any neurological deficits. At first, multiple brain tumors were suspected based on findings from magnetic resonance imaging of the brain. However, serological and cerebrospinal fluid tests for syphilis yielded positive results, and the masses were reduced using amoxicillin. Multiple cerebral syphilitic gummas were therefore diagnosed. High-dose penicillin therapy was initiated and syphilitic gummas disappeared after five months. Treponema pallidum could invade the central nervous system at an early phase, and sometimes may be difficult to distinguish from malignant brain tumor. If intracranial lesions are identified in a syphilis-infected patient, cerebral syphilitic gumma should be considered as a differential diagnosis.

JAK2 V617F Mutation and Large Cerebral Artery Disease in Patients with Myeloproliferative Neoplasms.

AIM: The aim of the present study was to clarify the association between the Janus kinase 2 (JAK2) V617F mutation and large cerebral artery disease (LCAD) in patients with myeloproliferative neoplasms (MPNs). METHODS: We retrospectively analysed patients diagnosed with MPNs between June 1992 and June 2022 who underwent brain magnetic resonance imaging. LCAD was defined as extracranial or intracranial large artery stenosis (≥ 50%) or occlusion on magnetic resonance angiography. RESULTS: A total of 86 patients (47 males; median age, 69 years old) were enrolled in this study. JAK2 V617F mutation was detected in 63 (73.3%) patients and LCAD in 35 (40.7%) patients. Univariate analysis showed that history of ischaemic stroke (LCAD, 62.9% vs. non-LCAD, 11.8%; P＜0.001), JAK2 V617F mutation (91.4% vs. 60.8%, P=0.002), and age ≥ 60 years (85.7% vs. 60.8%, P=0.016) were significantly associated with LCAD. Multiple logistic regression analysis showed that, in addition to ischaemic stroke, age ≥ 60 years and diabetes mellitus, JAK2 V617F mutation (odds ratio 29.2, 95% confidence interval 1.2-709.8, P=0.038) was independently associated with LCAD. LCAD was frequently observed in the intracranial carotid (14/35, 40.0%) and middle cerebral (13/35, 37.1%) arteries. CONCLUSIONS: This study revealed a significant association between the JAK2 V617F mutation and LCAD in patients with MPNs. This suggests that the JAK2 V617F mutation may promote cerebrovascular atherosclerosis and could be very important in determining therapeutic strategies for patients with not only JAK2 V617F-mutated MPNs but also LCAD-related stroke.

[Progressive multifocal leukoencephalopathy in a patient with rheumatoid arthritis under salazosulfapyridine treatment].

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by JC virus (JCV) activation. We report an 85-years old man who had been diagnosed to have rheumatoid arthritis (RA) 1.5 years prior to diagnosis of PML, and had been treated with salazosulfapyridine (SASP). He developed weakness of the left upper limb, which progressed gradually for two months. A neurological examination on admission revealed severe palsy of the left upper limb without sensory disturbance, cognitive decline or gait disturbance. Brain MRI revealed white matter lesions in the right frontal lobe around the precentral gyrus. Cerebrospinal fluid (CSF) examination and peripheral lymphocyte counts were normal. HIV was ruled out serologically. There were no findings suggestive of malignancy. We suspected PML and stopped SASP. JCV-DNA was detected in CSF. There were enlarged nuclei positive with VP-1 immunostaining in the brain biopsy materials. Thus, the diagnosis of PML was definitive. Paralysis of the left upper limb began to improve one week after discontinuing SASP. Treatment with mefloquine and mirtazapine was initiated, but he developed severe interstitial pneumonia, which might be caused by mefloquine. Therefore, he underwent rehabilitation without medication. JCV-DNA became undetectable and white matter lesions decreased 6 months later. Paralysis improved and he had no problem with activities of daily living a year later. The risk factor for PML has changed over the last decade, and drugs such as biologics became significant risk factors for patients with autoimmune diseases. There are reports suggesting that systemic lupus erythematosus (SLE) and RA themselves might be independent risk factors for PML. Although there is no previous report of SASP inducing PML, SASP might be the culprit in our case. However, there is another possibility that SAPS and RA worked synergistically for the onset of PML.

Lambert-Eaton Myasthenic Syndrome Caused by Nivolumab in a Patient with Squamous Cell Lung Cancer.

Lambert-Eaton myasthenic syndrome (LEMS) is a representative paraneoplastic neurological syndrome. Recently, nivolumab, an anti-programmed cell death 1 inhibitor, has been approved for advanced non-small-cell lung cancer. Careful attention should be paid to immune-related adverse events (irAEs), including neurotoxicity. We herein report a 73-year-old woman with LEMS that occurred during nivolumab treatment for pulmonary squamous cell carcinoma. After the 20th week of nivolumab, she experienced various neurological symptoms such as ptosis, lower limb weakness, and photophobia. Findings from a nerve conduction study and a positive anti-P/Q-type voltage-gated calcium channel antibody made a diagnosis of LEMS. Pyridostigmine and 3,4-diaminopyridine temporarily improved her symptoms. This was the first case of LEMS as a neurological irAE. LEMS should be considered as a possible neurological irAE.

[Extended voriconazole theraphy and long term survival of a patient with invasive central aspergillosis causing stroke].

Central nervous system (CNS) aspergillosis with stroke has a high mortality and poor prognosis generally. We report a 78-years-old woman with diabetes mellitus, who developed invasive paranasal sinus aspergillosis with the orbital apex syndrome on the right side and cerebral infarction caused by intracranial occlusion of the right internal carotid artery. Based on the presence of a mass lesion in the ethmoid sinus extending to the orbital apex on the right side with cranial CT, the mass lesion was surgically removed and the pathological examination of the surgical specimen revealed aspergillus mold. Immediately after surgery, we initiated treatment with voriconazole 200 mg × 2/day intravenously for 38 days, and then via feeding tube for 86 days until the galactomannan-aspergillus antigen level in the cerebrospinal fluid became negative at 132 days. She is alive now for almost two years without relapse of aspergillosis. There is no definitive guideline for management of patients with CNS aspergillosis concerning the length of drug treatment and the method for monitoring the response for treatment. We believe that measurement of the galactomannan-aspergillus antigen level in the cerebrospinal fluid might be a useful way of monitoring the efficacy of treatment for CNS aspergillosis.