Efficacy and safety of Infliximab for steroid-resistant immune-related adverse events: A retrospective study.

The present study investigated outcomes of infliximab (IFX) treatment among 8 Japanese patients with various types of cancer (4 with malignant melanoma, 3 with lung cancer and 1 with renal cancer) who developed severe steroid-resistant immune-related adverse events (irAEs) in association with immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Specific ICIs used were anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibody preparations in 7, 2 and 5 patients, respectively. Specific irAEs included grade 3 diarrhea/colitis in 7 patients and disseminated intravascular coagulation and myocarditis attributed to autoimmune activation in 1 patient. The median duration between systemic steroid and IFX treatments was 9 (range, 2-39) days. A total of 3 patients responded to IFX, 1 of whom responded after one dose and 2 responded after two doses. Respective diseases improved to grade 0 after a median of 18 (range, 9-32) days. No AEs were attributable to IFX. Additionally, anti-cytomegalovirus (CMV) and antibacterial agents were administered in parallel given the presence of CMV and Clostridium difficile (CD) infections in all patients, except in 1 exhibiting a marked IFX response after one dose. The combination of highly immunosuppressive IFX and high-dose systemic steroid administration over a long period presumably predisposed the patients to opportunistic enteric infections. Accordingly, early initiation of IFX treatment in conjunction with systemic steroid therapy should be considered for severe diarrhea/colitis and other irAEs. However, the possibility for CMV and CD infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.

Imaging of Triglycerides in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy.

Native triglycerides (TG) deposited in the human vascular wall is not measurable or visible in vivo to date. We discovered that by exciting fluorescence at 345 nm and emitting at 420 nm, 3-amino-4-hydroxy-5-nitrobenzene sulfonic acid monohydrate (3-ANA) elicits a brown fluorescence that is characteristic of just TG. Therefore, localization of TG in coronary plaques and normal segments that were obtained from 19 human autopsy cases was examined by color fluorescent angioscopy (CFA) and microscopy using 3-ANA as a biomarker of TG. By CFA, the percentage (%) incidence of TG in 23 normal segments, 13 white plaques without lipid deposition, 18 white plaques (growth stage) with lipid deposition, 11 yellow plaques without necrotic core (mature stage), and 12 yellow plaques with necrotic core (advanced mature stage) was 95, 92, 50, 27, and 25, respectively. By color fluorescent microscopy, TG deposited mostly in the fibrotic area of the plaques. Contrary to the general belief that TG amount increases with plaque maturation, the results indicated that TG was deposited in most of the normal coronary segments, but the amount decreased with plaque maturation. If 3-ANA becomes applicable clinically, the CFA system could be used for imaging TG within coronary plaques in patients in vivo.

Molecular Imaging of Native Low-Density Lipoprotein by Near-Infrared Fluorescent Angioscopy in Human Coronary Plaques.

Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease, but its localization within the human coronary arterial wall is poorly understood. Imaging of LDL in 30 coronary arteries excised from 15 subjects who underwent autopsy was performed using near-infrared fluorescent angioscopy system and using indocyanine green dye as a biomarker of LDL. The percentage incidence of LDL in 28 normal segments, 24 white plaques (early stage of plaque growth), and 21 yellow plaques (mature stage of plaque) classified by conventional angioscopy, was 14.2, 79.1 (p <0.01 vs normal segments and p <0.05 vs yellow plaques), and 28.5, respectively. Coronary near-infrared fluorescent angioscopy showed similar results in 7 patients in vivo. Our results suggested that LDL begins to deposit in the human coronary arterial wall in the early stage of atherosclerosis, increasingly deposits with plaque growth and decreases in the mature stage; and therefore, molecular therapy targeting LDL should be started before plaque maturation.

[Clinical evaluation of vertigo in menopausal women].

Vertigo is one of the usual menopausal symptoms. We have often examined some women under the complaint of vertigo related with the menopause. We diagnosed each disease based on neuro-otological examinations and investigated the characteristics of menopausal-associated vertigo. We studied 413 women aged 40-59 years old who complained of vertigo. There were 73 women with menopause symptoms (14 women introduced from the gynecologist in our medical center, 18 women had undergone treatment at another female clinic, and 41 women visited an otorhinolaryngologist first) compared with 340 women without menopause symptoms. In the menopause group, 41 (56.2%) cases were diagnosed as having benign paroxysmal positional vertigo (BPPV), 13 (17.8%) cases had Meniere's disease, sudden deafness with vertigo accounted 2 cases, one was an acoustic tumor, and so on. The percentage of patients with BPPV was almost same ratio between the menopause group (56.2%) and the non-menopause group (52.9%). The percentage of patients with Meniere's disease was higher markedly in the menopausal group (17.8%). than the non-menopause group (9.7%). Menopausal symptoms are caused not only by hot flashes related to a lack of estrogen but also by psychological factors. The onset of Meniere's disease can also be influenced by psychological factors. As for the diagnosis of Meniere's disease, we supposed the reason for the higher percentage in the menopausal group was its relationship with psychological factors. We could diagnose and treat some menopausal women with vertigo. We believe that joint consultation with a gynecologist and otorhinolaryngologist would be necessary to ensure an optimum quality of life for such patients.

VGCC antibody-positive paraneoplastic cerebellar degeneration presenting with positioning vertigo.

A 70-year-old woman developed paraneoplastic cerebellar degeneration (PCD) due to P/Q-type and N-type voltage-gated calcium channel antibodies and small cell lung cancer, the main clinical manifestations of which were severe positioning vertigo and vomiting. Loss of the visual suppression of caloric nystagmus, spontaneous downbeat nystagmus, periodic alternating nystagmus, and positioning vertigo in our patient most probably corresponds to the cerebellar flocculus/paraflocculus lesion caused by PCD.

[3D-CT highly useful in diagnosing foreign bodies in the paraesophageal orifice].

Multislice computed tomography (CT) enables rapid, easy construction of 3-dimensional CT images (3D-CT), aiding diagnostic imaging. 3D-CT is reported to be highly useful in diagnosing temporal bone disorders, in otorhinolaryngology, especially abnormal shape and the ossicular chain of the auditory ossicles and facial bone fractures. Given the complexity of laryngeal anatomy, 3D-CT is useful in diagnosing the extent of infiltration of laryngeal cancer and in examining vocal cord movement, which is difficult to evaluate by conventional CT, magnestic resonance imaging (MRI), and fiberscopy. Among patients seen for a suspected foreign body between June 2002 and May 2003, we chose 3 in whom laryngoscopy at the first examination could not detect a foreign body but in whom symptoms and findings suggested such presence in the paraesophageal orifice. In all 3 cases, 3D-CT imaging showed the size, length, location, and direction of the foreign body, providing information useful for the surgical approach.