Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

Impact of pre-Treatment C-reactive protein level and skeletal muscle mass on outcomes after stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer: A supplementary analysis of the Japan Clinical Oncology Group study JCOG0403

This study aimed to evaluate the impact of pretreatment C-reactive protein (CRP) and skeletal muscle mass (SMM) on outcomes after stereotactic body radiotherapy (SBRT) for T1N0M0 non-small cell lung cancer (NSCLC) as a supplementary analysis of JCOG0403. Patients were divided into high and low CRP groups with a threshold value of 0.3 mg/dL. The paraspinous musculature area at the level of the 12th thoracic vertebra was measured on simulation computed tomography (CT). When the area was lower than the sex-specific median, the patient was classified into the low SMM group. Toxicities, overall survival (OS) and cumulative incidence of cause-specific death were compared between the groups. Sixty operable and 92 inoperable patients were included. In the operable cohort, OS significantly differed between the CRP groups (log-rank test p = 0.009; 58.8% and 83.6% at three years for high and low CRP, respectively). This difference in OS was mainly attributed to the difference in lung cancer deaths (Gray’s test p = 0.070; 29.4% and 7.1% at three years, respectively). No impact of SMM on OS was observed. The incidence of Grade 3–4 toxicities tended to be higher in the low SMM group (16.7% vs 0%, Fisher’s exact test p = 0.052). In the inoperable cohort, no significant impact on OS was observed for either CRP or SMM. The toxicity incidence was also not different between the CRP and SMM groups. The present study suggests that pretreatment CRP level may provide prognostic information in operable patients receiving SBRT for early-stage NSCLC

The significance of extended lymphadenectomy for colorectal cancer with isolated synchronous extraregional lymph node metastasis

SummaryBackground/ObjectiveThe significance of extended lymphadenectomy for colorectal cancer with extraregional lymph node metastasis, such as para-aortic lymph node metastasis, has not been established. The purpose of this study was to evaluate the significance of extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis.MethodsBetween July 2004 and December 2013, 16 patients with synchronous extraregional lymph node metastasis without other organ metastases underwent curative resection and extended lymphadenectomy (R0 group). The clinical characteristics and survival outcomes of the R0 group were compared with those of 12 patients with extraregional lymph node metastasis who underwent palliative surgery (control group).ResultsIn the R0 group, the 5-year cancer-specific survival (CSS) rate was 70.3% and the 5-year relapse-free survival (RFS) rate was 60.5%. The 5-year CSS differed significantly between the R0 and control groups (70.3% vs. 12.5%; p = 0.0003). Univariate analyses revealed that the total numbers of metastatic lymph nodes and metastatic regional lymph nodes present were significantly associated with RFS (p = 0.019 for both).ConclusionFindings from our study suggest that extended lymphadenectomy for colorectal cancer with synchronous isolated extraregional lymph node metastasis might be effective in carefully selected patients

Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors

睡眠中の脳のリフレッシュ機構を解明. 京都大学プレスリリース. 2021-08-27.Sleep is generally viewed as a period of recovery, but how the supply of cerebral blood flow (CBF) changes across sleep/wake states has remained unclear. Here, we directly observe red blood cells (RBCs) within capillaries, where the actual substance exchange between the blood and neurons/glia occurs, by two-photon microscopy. Across multiple cortical areas, average capillary CBF is largely increased during rapid eye movement (REM) sleep, whereas it does not differ between periods of active wakefulness and non-REM sleep. Capillary RBC flow during REM sleep is further elevated following REM sleep deprivation, suggesting that capillary CBF reflects REM sleep pressure. At the molecular level, signaling via adenosine A2a receptors is crucial; in A2a-KO mice, capillary CBF upsurge during REM sleep is dampened, and effects of REM sleep pressure are abolished. These results provide evidence regarding the dynamics of capillary CBF across sleep/wake states and insights to the underlying mechanisms

Milk product intake, muscle strength, and NFKB methylation

Background Muscle atrophy with aging is closely associated with chronic systemic inflammation and lifestyle-related diseases. In the present study, we assessed whether post-exercise milk product intake during 5-month interval walking training (IWT) enhanced the increase in thigh muscle strength and ameliorated susceptibility to inflammation in older women. Methods Subjects [n = 37, 66±5 (standard deviation) yrs] who had been performing IWT for >6 months participated in this study. They were randomly divided into the following 3 groups: IWT alone (CNT, n = 12), IWT + low-dose post-exercise milk product intake (LD, n = 12; 4 g protein and 3 g carbohydrate) or IWT + a 3-times higher dose of milk product intake than the LD group (HD, n = 13). They were instructed to repeat ≥5 sets of fast and slow walking for 3 min each at ≥70% and 40% peak aerobic capacity for walking, respectively, per day for ≥4 days/week. Results After IWT, thigh muscle strength increased in the HD group (8±2%) more than in the CNT group (-2±3%, P = 0.022), despite similar IWT achievements between the groups (P>0.15). Pyrosequencing analysis using whole blood showed that methylation of NFKB1 and NFKB2, master genes of inflammation, was enhanced in the HD group (29±7% and 44 ±11%, respectively) more than in the CNT group (-20±6% and -10±6%, respectively; P<0.001). Moreover, the genome-wide DNA methylation analysis showed that several inflammation-related genes were hyper-methylated in the HD group compared with that in the CNT group, suggesting greater pro-inflammatory cytokine gene suppression in the HD group. Conclusion HD milk product intake after exercise produced a greater percent increase in thigh muscle strength and NFKB1 and NFKB2 gene methylation during IWT in physically active older women

Current state of therapeutic development for rare cancers in Japan, and proposals for improvement

This article discusses current obstacles to the rapid development of safe and effective treatments for rare cancers, and considers measures required to overcome these challenges. In order to develop novel clinical options for rare cancers, which tend to remain left out of novel therapeutic development because of their paucity, efficient recruitment of eligible patients, who tend to be widely dispersed across the country and treated at different centers, is necessary. For this purpose, it is important to establish rare cancer registries that are linked with clinical studies, to organize a central pathological diagnosis system and biobanks for rare cancers, and to consolidate patients with rare cancers to facilities that can conduct clinical studies meeting international standards. Establishing an all‐Japan cooperative network is essential. Clinical studies of rare cancers have considerable limitations in study design and sample size as a result of paucity of eligible patients and, as a result, the level of confirmation of the efficacy and safety shown by the studies is relatively low. Therefore, measures to alleviate these weaknesses inherent to external conditions need to be explored. It is also important to reform the current research environment in order to develop world‐leading treatment for rare cancers, including promotion of basic research, collaboration between industry and academia, and improvement of the infrastructure for clinical studies. Collaboration among a wide range of stakeholders is required to promote the clinical development of treatment for rare cancers under a nationwide consensus

Hepatobiliary cystadenoma exhibiting morphologic changes from simple hepatic cyst shown by 11-year follow up imagings

<p>Abstract</p> <p>Background</p> <p>A long-term follow up case of hepatobiliary cystadenoma originating from simple hepatic cyst is rare.</p> <p>Case presentation</p> <p>We report a case of progressive morphologic changes from simple hepatic cyst to hepatobiliary cystadenoma by 11 – year follow up imaging. A 25-year-old man visited our hospital in 1993 for a simple hepatic cyst. The cyst was located in the left lobe of the liver, was 6 cm in diameter, and did not exhibit calcification, septa or papillary projections. No surgical treatment was performed, although the cyst was observed to gradually enlarge upon subsequent examination. The patient was admitted to our hospital in 2004 due to epigastralgia. Re-examination of the simple hepatic cyst revealed mounting calcification and septa. Abdominal CT on admission revealed a hepatic cyst over 10 cm in diameter and a high-density area within the thickened wall. MRI revealed a mass of low intensity and partly high intensity on a T1-weighted image. Abdominal angiography revealed hypovascular tumor. The serum levels of AST and ALT were elevated slightly, but tumor markers were within normal ranges. Left lobectomy of the liver was performed with diagnosis of hepatobiliary cystadenoma or hepatobiliary cystadenocarcinoma. The resected specimen had a solid component with papillary projections and the cyst was filled with liquid-like muddy bile. Histologically, the inner layer of the cyst was lined with columnar epithelium showing mild grade dysplasia. On the basis of these findings, hepatobiliary cystadenoma was diagnosed.</p> <p>Conclusion</p> <p>We believe this case provides evidence of a simple hepatic cyst gradually changing into hepatobiliary cystadenoma.</p

Lovastatin insensitive 1, a novel pentatricopeptide repeat protein, is a potential regulatory factor of isoprenoid biosynthesis in Arabidopsis

Higher plants have two metabolic pathways for isoprenoid biosynthesis: the cytosolic mevalonate (MVA) pathway and the plastidal non-mevalonate (MEP) pathway. Despite the compartmentalization of these two pathways, metabolic flow occurs between them. However, little is known about the mechanisms that regulate the two pathways and the metabolic cross-talk. To identify such regulatory mechanisms, we isolated and characterized the Arabidopsis T-DNA insertion mutant lovastatin insensitive 1 (loi1), which is resistant to lovastatin and clomazone, inhibitors of the MVA and MEP pathways, respectively. The accumulation of the major products of these pathways, i.e. sterols and chlorophyll, was less affected by lovastatin and clomazone, respectively, in loi1 than in the wild type. Furthermore, the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity analysis showed higher activity of HMGR in loi1-1 treated with lovastatin than that in the WT. We consider that the lovastatin-resistant phenotype of loi1-1 was derived from this post-transcriptional up-regulation of HMGR. The LOI1 gene encodes a novel pentatricopeptide repeat (PPR) protein. PPR proteins are thought to regulate the expression of genes encoded in organelle genomes by post-transcriptional regulation in mitochondria or plastids. Our results demonstrate that LOI1 is predicted to localize in mitochondria and has the ability to bind single-stranded nucleic acids. Our investigation revealed that the post-transcriptional regulation of mitochondrial RNA may be involved in isoprenoid biosynthesis in both the MVA and MEP pathways.Peer reviewe