Background and purpose: Gain-of-function mutations in the C-terminal cytoplasmic domain of CCR4 caused by somatic mutations in the corresponding region of the CCR4 gene are often found in adult T-cell leukemia/lymphoma (ATLL), and such mutations have been suggested to affect the efficacy of the humanized anti-CCR4 monoclonal antibody mogamulizumab. In this study, we investigated whether CCR4 aberration correlated with the clinical features and immunophenotypes of neoplastic cells in ATLL patients treated at our institution. Methods: Among ATLL patients treated at our institution between 1993 and 2021, we selected 20 in whom the unusual cell population (UCP) comprised ≥ 40% of the entire cell population within the materials analyzed by multi-color flow cytometry (M-FCM). CCR4 aberrations were assayed by polymerase chain reaction (PCR)/direct sequencing targeting the hot-spot region, and fragment analysis was performed to confirm the deletion within the gene. Furthermore, we evaluated the performance of a heteroduplex mobility assay for detecting aberrations. Results: Eight (40%) of the 20 patients carried aberrations in CCR4, including nonsense mutations (2 Q330* and 4 Y331^*) in 6 and copy number increase in a variant allele representing a single nucleotide polymorphism in one. The remaining patient had a missense mutation (Q336H) associated with the deletion of Q336–T342 and fragment analysis confirmed the deletion of 18 nucleotides. Of 8 patients with CCR4 aberrations, heteroduplex bands were found in 6. Regarding subtypes of ATLL, 6 (55%) of 11 cases of the acute type and 2 (40%) of 5 cases of the lymphoma type carried aberrations, whereas no aberration was found in 4 chronic/smoldering cases. Of 8 cases expressing ++ CCR4 by M-FCM, 4 (50%) carried nonsense mutations. Conversely, of 6 with nonsense mutations, 4 (67%) expressed ++ levels of CCR4. One patient with a nonsense mutation was administered mogamulizumab for relapsed/refractory disease, resulting in a partial response. Conclusion: This study suggests that the level of CCR4 expression is associated with nonsense mutations in CCR4. To elucidate the relationship between CCR4 aberration and efficacy of mogamulizumab, prospective clinical studies incorporating the expression of CCR4 and %UCP determined by M-FCM are required.

Objectives: Appropriate meal forms and the provision of thickeners for liquid have been recommended for patients with dysphagia. The dysphagia diet committee of the Japanese Society of Dysphagia Rehabilitation issued a three-level standard for thickened water, but there is no standard for liquid nutrition. The thickening of liquid nutrition differs depending on the variety of nutrients and the thickness is often evaluated subjectively. This study aimed to establish a standard for the thickening of liquid nutrition in our hospital, and to create an adjustment manual based on subjective and objective evaluations of thickening viscosity. Therefore, we examined the method of adjusting the thickening of liquid nutrition and thickeners adopted in hospitals. Methods: The thickened water using softia^®S was compared subjectively and using objective methods such as the Flow test and Line Spread Test (LST). We also examined the stirring method for thickening enteral nutrition and the duration of standing, and conducted subjective evaluation by multiple occupations and objective evaluation by the Flow test. A manual on thickening was prepared and distributed, and a questionnaire survey covering eight items was conducted ten months later. Results: Although there was a tendency to overestimate the amount of thickened water subjectively, the Flow test and LST values accurately reflected the standard amount of softia^®S added. There were differences in the amount of softia^®S added depending on the type of liquid nutrition and the degree of thickening increased with the amount of time left standing after mixing. The subjective evaluation varied among the examiners, but the Flow test demonstrated a consistent trend and was a useful evaluation method. There was a difference in the frequency of use of thickening agents in the questionnaire survey and 63% of the respondents complied with the precautions. Conclusion: The Flow test, a simple objective evaluation method, can be used to review the ambiguity of subjective evaluation when developing a hospital standard method for thickening liquid nutrition products. As the viscosity of liquid nutrition varies depending on the method of thickening, it is necessary to provide information and education to the ward nursing staff on the employed adjustment method.

We describe a single case of a patient with ALK-positive large B-cell lymphoma (ALK+ LBCL) treated in our hospital. The patient was a 61-year-old man who initially presented with a stage III disease involving systemic lymph nodes (LNs), which was diagnosed with immunoblastic lymphoma. He readily responded to 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), achieving a long-term complete response. After 5 and a half years, he relapsed with the involvement of left axillary LNs. A biopsy revealed the proliferation of immunoblasts or plasmablasts, which were positive for ALK immunohistochemistry (IHC) with a granular and restricted cytoplasmic staining pattern. The cells were CD20⁻, cytoplasmic immunoglobulin κ⁺, and CD138⁺. Review of the first biopsy confirmed similar IHC results. Cytogenetic and molecular analyses demonstrated t(2;17)(p23;q23), which generated the CLTC-ALK fusion gene. The relapsed lesions were resolved by regional radiotherapy, and the patient is currently free from lymphoma 13 years after the initial presentation. This case report suggests that the outcome of advanced-stage ALK+ LBCL is not necessarily poor and that the disease can be controlled by conventional chemoradiotherapy.

Purpose: In order to establish an optimal tube feeding method that does not cause diarrhea, we performed a literature review and explored unresolved issues recognized by previous studies. Methods: We accessed the web site of Japan Medical Abstracts Society and selected a total of 60 articles on nursing care written in Japanese between 1985 and 2017 using the keywords “tube feeding” and “bowel movement”. Results: 1) Changes in the number of articles: The first article was published in 1991, 2–6 articles were published annually from 2002, and after peaking at 8 articles in 2007, 1–7 articles were published annually. 2) Research method: There were 31 case-oriented studies and 29 quantitative studies. 3) Research content: Most of the studies were on "nutrients", demonstrating that the nutrients to be injected should be around room temperature, that diarrhea was improved by injecting semi-solid materials, and that nutritional supplements containing guar gum decomposition products, which produced short-chain fatty acids, were useful for improving diarrhea and constipation by suppressing the growth of pathogenetic bacteria and improving the intestinal environment. Studies on "injection method" reported that even if the injection rate was 400 to 800 ml per 30 min, there was no effect on gastrointestinal symptoms or vital signs, and that administration of water before injecting nutrients was effective at shortening the gastric retention and discharge time, at reducing the gastric volume, and at relieving the internal gastric pressure. Studies on "thickeners" reported that agar was the most effective, had high coagulation activity even in a small amount, and had unique characteristics in that it is able to remain solid in the stomach but be rapidly disintegrated in the intestine. Studies on foodstuffs reported that dietary fiber promotes mobility in the large intestine and that lemon juice has protein coagulating effects. Other studies included creation of a manual to initiate nutrition with solidified materials and appropriate cleaning methods of instruments focusing on bacterial contamination in injection materials. Conclusion: Although continuing research over the past 30 years has provided effective nutritional supplements and injection methods for controlling bowel movement in tube-fed patients, optimal tube feeding methods have not yet been established. Further studies are needed to clarify the causes of bowel movement problems by assessing the individual factors in each tube-fed patient.

It has been reported that sleep disturbance in the elderly is associated with increased cardiovascular risk, development of hypertension, impaired glucose tolerance and depressive symptoms, but what about its effect on cognitive decline and the development of dementia? Tsapanou et al. reported that sleep deprivation is associated with the development of dementia, and the mechanism is thought to be that sleep disturbance reduces the clearance of amyloid-β (Aβ) in the cerebrospinal fluid, causing an increase of Aβ and its deposition, which increases the risk of Alzheimer's disease. Billioti de Gage et al. reviewed 10 studies on the association between benzodiazepine use and dementia risk, and found that benzodiazepines increased the risk of dementia by 1.5-2 times. However, Gray et al. reported that there was an increased risk of dementia at low and moderate doses of benzodiazepines, but not at higher doses. In addition, Imfeld et al. reported that when benzodiazepines are used in the prodromal phase of dementia onset, the risk of developing dementia is increased. It is thought that benzodiazepines are used to treat sleep disturbances that occur during the prodromal phase of dementia, and as a result, benzodiazepines could be perceived as being associated with the development of dementia. Thus, no clear conclusion has been reached about the increased risk of dementia due to the use of benzodiazepines. The treatment of sleep disorders includes pharmacological treatments such as benzodiazepines, non-benzodiazepines, melatonin receptor agonists, and orexin receptor antagonists, as well as non-pharmacological approaches such as modifying sleep habits. Taking into account the relationship between sleep disturbance and dementia, treatment of insomnia should be based on a balanced combination of each.