Influence of using history of immune checkpoint inhibitor therapy for neutropenia caused by combination therapy of ramucirumab and docetaxel.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (p = 0.037). The pretreatment history of ICI therapy affects the incidence of neutropenia caused by RAM + DTX therapy in patients with NSCLC.

Pulmonary vein isolation under direct visual identification of the left atrium-pulmonary vein junction using intra-cardiac echography.

INTRODUCTION: Intra-cardiac echocardiography (ICE) which has some benefits, can be used to obtain detailed anatomy of the heart chambers or large vessels, and the catheter positions, and it has been considered useful for improving the outcome of the ablation. In the present study, we performed pulmonary vein isolation (PVI) under real time monitoring of ICE imaging utilizing an ICE catheter placed at the junction of the left atrium (LA) and PVs (LA-PV junction). METHODS: PVI for atrial fibrillation (AF) was performed in 30 cases with drug-resistant AF (mean age: 66-years-old; including 22 males). An ICE catheter utilizing a 9 MHz frequency was inserted into the LA via the atrial septum, and placed at the LA-PV junction. Circumferential ablation was performed in the LA outside of the PV ostium, encircling both the superior and inferior ostia together under ICE imaging. RESULTS: The anatomy of the LA to the PVs and catheter sites were clearly identified by the ICE during the procedure, which enabled a precise and safe catheter manipulation with minimal fluoroscopy. Further, the wall thickness of the PV and LA, and position of the esophagus could be obtained by ICE, facilitating care in adjusting the power and/or duration of the current delivery. CONCLUSION: ICE imaging of the LA-PV junction permitted real time monitoring of the target sites for PVI during the ablation procedure, and was considered a useful technique for performing PVI.

Mediastinoscopic extended thymectomy for pediatric patients with myasthenia gravis.

BACKGROUND: Extended thymectomy is indicated for children with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for mediastinoscopic extended thymectomy (MET) on children with MG. METHOD: A total of 14 children underwent MET at Kanagawa Children's Medical Center between 2005 and 2013. A mediastinal operation field was made by a V-shaped hook infrasternally to extirpate the thymus with adipose tissue around the thymus. RESULTS: The operation time and the amount of blood loss were 182±44 minutes and 34±43 ml, respectively. Postoperative complications, in the form of transient paralysis of the right recurrent nerve, occurred in 2 patients. The median length of postoperative hospital stay was 4.5 days. After MET, 6 patients achieved complete remission and 7 patients achieved steroid dose reduction, but no improvement was seen in 1 patient. CONCLUSIONS: This procedure offers the advantage of good surgical access for dissection around the bilateral phrenic nerves in extended total thymectomy, while achieving good cosmetic results.

Epidemiology of infantile autism in southern Ibaraki, Japan: differences in prevalence in birth cohorts.

Infantile autism was diagnosed by DSM-III criteria in 132 children (26 girls) who were outpatients of the Tsuchiura Child Guidance Center during the years 1977-1985. The children, all Japanese except for one Laotian boy born in Laos, were classified according to year and month of birth. The prevalence rate of infantile autism in southern Ibaraki, Japan, within the birth cohort born between 1972 and 1978 was 13.9/10,000 children. The month of birth for infantile autism increased in the second quarter of the year. The prevalence rate of infantile autism in each 1-year birth cohort fluctuated in a 4-year cycle, which was closely correlated (r = .92) with the number of children admitted with pneumonia and bronchiolitis in that area. These findings led us to postulate that infectious factors of children's pneumonia and bronchiolitis may have some role in the cause of infantile autism.

Coronary artery bypass grafting for coronary aneurysms due to Kawasaki disease.

We report a 23-year-old man who underwent coronary artery bypass grafting (CABG) for coronary aneurysms associated with Kawasaki disease using the left internal thoracic artery (LITA) and right gastroepiploic artery (RGEA) after a second myocardial infarction (MI). Preoperatively, this patient showed repetitive occlusion and recanalization of coronary artery flow without coronary stenosis. Indication of bypass surgery in Kawasaki disease is usually associated with stenosis. However, even an aneurysm alone should be an indication of surgery if there is any kind of ischemic event.

[Mitral valve replacement with concomitant coronary bypass for the papillary muscle rupture after acute myocardial infarction in situs inversus].

A 53-year-old man, who was known to have situs inversus totalis all of his life, had acute myocardial infarction complicated by partial rupture of the posterior papillary muscle causing mitral regurgitation and pulmonary edema. The patient underwent mitral valve replacement (Omnicarbon 27 mm) with concomitant aortocoronary saphenous vein bypass, and he is now doing well 9 months following the operation. To our knowledge, this is the first case of the successful mitral valve replacement and concomitant aortocoronary saphenous vein bypass on a patient with situs inversus totalis (mirror-image dextrocardia) in Japan.

[Lung cancer with small intestine metastasis characterized by exceptionally high levels of serum CA 19-9].

A 59-year-old man was given a diagnosis of lung cancer (moderately differentiated tubular adenocarcinoma) with left adrenal gland and bone metastases in January 1997, and received chemotherapy and irradiation therapy. In late May, anemia and occult blood were detected, with a marked increase in serum CA 19-9. In August, the patient was admitted to our department complaining of melena. His serum CA 19-9 level on admission was significantly elevated (18,960 U/ml). After admission, symptoms of ileus developed. Radiographs of the small intestine and abdominal computed tomographic scans suggested the presence of a tumor in the small intestine. Therefore, surgery was performed, revealing a tumor in the jejunum, which was histologically diagnosed as metastasis of lung cancer to the small intestine. Immunohistochemical staining for CA 19-9 was more intense in specimens from the small intestine tumor than from lung cancer specimens. Serum CA 19-9 decreased significantly after resection. The clinical course and results of CA 19-9 staining suggested that CA 19-9 production by the metastatic lesion in the small intestine was the major cause of the patient's high serum CA 19-9 level. This appears to be a rare case because, to our knowledge, there are no previous reports in the Japanese literature on patients with small intestine metastasis from lung cancer showing an exceptionally high level of serum CA 19-9.

Role of spectral cues in median plane localization.

The role of spectral cues in the sound source to ear transfer function in median plane sound localization is investigated in this paper. At first, transfer functions were measured and analyzed. Then, these transfer functions were used in experiments where sounds from a source on the median plane were simulated and presented to subjects through headphones. In these simulation experiments, the transfer functions were smoothed by ARMA models with different degrees of simplification to investigate the role of microscopic and macroscopic patterns in the transfer functions for median plane localization. The results of the study are summarized as follows: (1) For front-rear judgment, information derived from microscopic peaks and dips in the low-frequency region (below 2 kHz) and the macroscopic patterns in the high-frequency region seems to be utilized; (2) for judgment of elevation angle, major cues exist in the high-frequency region above 5 kHz. The information in macroscopic patterns is utilized instead of that in small peaks and dips.

Adaptive feedback cancellation with frequency compression for hearing aids.

The use of an adaptive feedback canceler (AFC) for howling suppression in hearing aids seems very attractive since it is not only unaffected by the changes in the operating environment, but it also limits signal degradation due to the feedback signal. This, however, requires a reference signal which is correlated with the feedback signal but not with the input signal. In hearing aids, such a signal is hard to obtain. The output signal could be used as reference if its correlation with the input signal could sufficiently be removed. If the reference signal is correlated with the input signal, the input signal will also be canceled by the AFC. Here, the use of a frequency compressor as a decorrelator is proposed. The performance of this system is then investigated via digital simulation. Results indicated that with the use of the proposed system and the proper choice of system parameters, an increase of about 18 dB in the howling margin could be achieved with minimal deterioration in output signal quality.

Production of leukotriene B4 in parenchymal and sinusoidal cells of the liver in rats treated simultaneously with D-galactosamine and endotoxin.

A study was conducted to investigate production rate of leukotriene B4 (LTB4) in parenchymal and sinusoidal liver cells of rats with acute hepatic failure (AHF). AHF was induced by simultaneous administration of D-galactosamine (GalN) and endotoxin (LPS), and parenchymal as well as sinusoidal liver cells were isolated by collagenase perfusion method. Following preincubation for 15 min, isolated cellular fractions were incubated with Ca-ionophore (2 microM) for 5 min, and levels of LTB4 in culture media before and 5 min after addition of Ca-ionophore were analyzed by HPLC. Following results were obtained: The production rate of LTB4 was found to be the highest in Kupffer cells (7.2ng/10(6) cells/5 min), followed by endothelial cells (1.1), stellate cells (0.2) and parenchymal cells (not detectable). The production rate of LTB4 in both Kupffer cells and endothelial cells was found to reach a maximum in the fraction isolated 60 min after administration of GalN and LPS. Treatment with AA861, one of the selective inhibitors of 5-lipoxygenase, was shown to reduce the production of LTB4 in Kupffer cells to 53% at 10(-7)M and above 99% at higher than 10(-5)M. In conclusion, the majority of LTB4 generated in the liver of rats with AHF was found to be synthesized in Kupffer cells and, to a lesser extent, in endothelial cells, and the enhanced production of LTB4 was found to be greatly inhibited by treatment with AA861.

Human milk bile-salt-stimulated lipase is extremely reactive with the monoclonal antibody 1CF11 which recognizes a human-specific carbohydrate antigen.

1CF11 (Kanamaru, Y. et al.; Biochem. Biophys. Res. Commun., 249, 618-623, 1998) is a monoclonal antibody obtained after being raised in a mouse by injection of human milk MUC1 mucin as the antigen. Its reactivity was found to be unique in that it only reacts with a carbohydrate epitope shared by glycoproteins in human secretions, while its chemical nature is still unknown. Since a glycoprotein of Mr 135,000 (135K) in human milk was found to react extremely strongly with this antibody, we intended in this study to isolate the glycoprotein by a combination of various chromatographic techniques and identify it. It is a human milk bile-salt-stimulated lipase. By comparison of its immunoreactivity and glycan structures so far reported with those of lactoferrin from human milk, it is suggested that the epitope recognized by mAb ICF11 could be a human-specific novel glycan.

Enhanced production of leukotriene B4 by peripheral blood mononuclear cells in patients with fulminant hepatitis.

The production rate of leukotriene B4 (LTB4) was measured using peripheral blood mononuclear cells (PBMC) in patients with fulminant hepatitis (FH) or other liver diseases. LTB4 in the culture media of PBMC under stimulation with Ca-ionophore was fractionated by HPLC and measured by radioimmunoassay. The production rate of LTB4 was elevated in 16 of 17 FH patients (3.3 +/- 0.2 ng/10(6) cells for 5 min), while the production was below detectable level in patients with acute or chronic hepatitis and in healthy controls. In FH patients, the highest production rate of LTB4 was observed in the initial period of the disease. Enhanced LTB4 production may indicate the primed state of PBMC--the primed mononuclear cells are regarded as participating in the development of massive liver necrosis and of other organ failures in FH.