Transcutaneous carbon dioxide suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.

Cancer cachexia causes skeletal muscle atrophy, impacting the treatment and prognosis of patients with advanced cancer, but no treatment has yet been established to control cancer cachexia. We demonstrated that transcutaneous application of carbon dioxide (CO2) could improve local blood flow and reduce skeletal muscle atrophy in a fracture model. However, the effects of transcutaneous application of CO2 in cancer-bearing conditions are not yet known. In this study, we calculated fat-free body mass (FFM), defined as the skeletal muscle mass, and evaluated the expression of muscle atrophy markers and uncoupling protein markers as well as the cross-sectional area (CSA) to investigate whether transcutaneous application of CO2 to skeletal muscle could suppress skeletal muscle atrophy in cancer-bearing mice. Human oral squamous cell carcinoma was transplanted subcutaneously into the upper dorsal region of nude mice, and 1 week later, CO2 gas was applied to the legs twice a week for 4 weeks and FFM was calculated by bioimpedance spectroscopy. After the experiment concluded, the quadriceps were extracted, and muscle atrophy markers (muscle atrophy F-box protein (MAFbx), muscle RING-finger protein 1 (MuRF-1)) and uncoupling protein markers (uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3)) were evaluated by real-time polymerase chain reaction and immunohistochemical staining, and CSA by hematoxylin and eosin staining. The CO2-treated group exhibited significant mRNA and protein expression inhibition of the four markers. Furthermore, immunohistochemical staining showed decreased MAFbx, MuRF-1, UCP2, and UCP3 in the CO2-treated group. In fact, the CSA in hematoxylin and eosin staining and the FFM revealed significant suppression of skeletal muscle atrophy in the CO2-treated group. We suggest that transcutaneous application of CO2 to skeletal muscle suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.

Appetite loss and associated factors at 1 year after intensive care unit elder survivors in a secondary analysis of the SMAP-HoPe study.

Appetite loss, a common but serious issue in older patients, is an independent risk factor for sarcopenia, which is associated with high mortality. However, few studies have explored the phenomenon of appetite loss after discharge from the intensive care unit (ICU). Therefore, we aimed to describe the prevalence of appetite loss and relationship between appetite loss and depression in patients living at home 12 months after intensive care. This study involved secondary analysis of data obtained from a published ambidirectional study examining post-intensive care syndrome 12 months after discharge (SMAP-HoPe study) conducted in 12 ICUs in Japan. We included patients aged > 65 years. The Short Nutritional Assessment Questionnaire and Hospital Anxiety Depression Scale were used for the analysis. Descriptive statistics and a multilevel generalized linear model were used to clarify the relationship between appetite loss and depression. Data from 468 patients were analyzed. The prevalence of appetite loss was 25.4% (95% confidence interval [CI], 21.5-29.4). High severity of depression was associated with a high probability of appetite loss (odds ratio, 1.2; 95%CI, 1.14-1.28; p = 0.00). Poor appetite is common 12 months after intensive care and is associated with the severity of depression.

Detection of bone marrow edema in differential diagnoses of odontogenic cysts using dual-energy computed tomography.

PURPOSE: In this study, we prospectively investigated the relationship between bone marrow edema (BME) and odontogenic cysts and explored the possibility of using dual-energy computed tomography (DECT) as an auxiliary tool for the diagnosis of odontogenic cysts. METHODS: This cross-sectional study included 73 patients who underwent the DECT scan and surgery for odontogenic cysts or odontogenic tumors. The virtual noncalcium (VNCa) computed tomography (CT) values and CT values were measured at several sites. The predictor variable was diagnosis, and the other variables included age, sex, and sites. The primary outcome was VNCa CT value. Variables were tested using the chi-square test or the Kruskal-Wallis test. The VNCa CT and CT values were tested using the Scheffe test for multiple comparisons. All variables were analyzed as independent variables affecting the VNCa CT values around the lesion in the multiple regression analysis. RESULT: There were 35 men and 38 women. The mean patient age was 50.0 ± 19.5 years (range: 8-86). The VNCa CT values (- 6.2 ± 34.3) around the lesion in patients with RCs were significantly higher than those in patients with dentigerous cysts (- 44.4 ± 28.6) and odontogenic keratocysts (- 67.3 ± 19.5). In multiple regression analysis, the VNCa CT values around the lesion showed a significant positive correlation with histological results (regression coefficient: - 0.605, P < 0.001). CONCLUSION: The presence of BME is associated with radicular cysts, and DECT can be used as an auxiliary tool for radicular cyst diagnosis.

Frequent tracheal suctioning is associated with extubation failure in patients with successful spontaneous breathing trial: a single-center retrospective cohort study.

BACKGROUND: Extubation failure, i.e., reintubation in ventilated patients, is a well-known risk factor for mortality and prolonged stay in the intensive care unit (ICU). Although sputum volume is a risk factor, the frequency of tracheal suctioning has not been validated as a predictor of reintubation. We conducted this study to examine whether frequent tracheal suctioning is a risk factor for reintubation. PATIENTS AND METHODS: We included adult patients who were intubated for > 72 h in the ICU and extubated after completion of spontaneous breathing trial (SBT). We compared the characteristics and weaning-related variables, including the frequency of tracheal suctioning between patients who required reintubation within 24 h after extubation and those who did not, and examined the factors responsible for reintubation. RESULTS: Of the 400 patients enrolled, reintubation was required in 51 (12.8%). The most common cause of reintubation was difficulty in sputum excretion (66.7%). There were significant differences in sex, proportion of patients with chronic kidney disease, pneumonia, ICU admission type, the length of mechanical ventilation, and ICU stay between patients requiring reintubation and those who did not. Multivariate analysis showed frequent tracheal suction (> once every 2 h) and the length of mechanical ventilation were independent factors for predicting reintubation. CONCLUSION: We should examine the frequency of tracheal suctioning > once every 2 h in addition to the length of mechanical ventilation before deciding to extubate after completion of SBT in patients intubated for > 72 h in the ICU.

Success of dental implants in patients with large bone defect and analysis of risk factors for implant failure: a non-randomized retrospective cohort study.

OBJECTIVES: This study aimed to retrospectively investigate the success and survival rates of dental implants used for dentomaxillary prostheses at our hospital and the risk factors associated with large bone defects. MATERIALS AND METHODS: A total of 138 external joint system implants used for dentomaxillary prostheses in 40 patients with large bone defects were included in this study. The alveolar bone at the site of implant insertion was evaluated using panoramic radiography and computed tomography. Various risk factors (demographic characteristics, dental status, and operative factors such as the employment of alveolar bone augmentation, the site, the length, and diameter of implants) for implant failure and complete implant loss were investigated using univariate and multivariate analyses. The associations between the variables and the success and survival rates of dental implants were analyzed using the multivariate Cox proportional hazard models. RESULTS: The 10-year overall success and survival rates were 81.3% and 88.4% in this study. Multivariable analysis showed that the male sex (HR 6.22), shorter implants (≤ 8.5 mm) (HR 5.21), and bone augmentation (HR 2.58) were independent predictors of success rate. Bone augmentation (HR 5.14) and narrow implants (≤ 3.3 mm) (HR 3.86) were independent predictors of the survival rate. CONCLUSION: Male sex, shorter or narrow implants, and bone augmentation were independent risk factors for dental implants used in dentomaxillary prostheses in patients with large bone defects. CLINICAL RELEVANCE: Clinicians should consider these risk factors and pay close attention to the management of these patients.

Non-clinical efficacy, safety and stable clinical cell processing of induced pluripotent stem cell-derived anti-glypican-3 chimeric antigen receptor-expressing natural killer/innate lymphoid cells.

The use of allogeneic, pluripotent stem-cell-derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator-initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cell (iPSC)-derived anti-glypican-3 (GPC3) chimeric antigen receptor (CAR)-expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder-free production of CAR-expressing NK/ILC cells from CAR-transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8-3.6 × 106 iPSC within 7 weeks was 1.8-4.0 × 109 . These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN-γ) production against GPC3-expressing tumor cells. When the CAR-NK/ILC cells were injected into a GPC3-positive, ovarian-tumor-bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non-clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR-NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell-based immune cell cancer therapies.

Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm.

During mammalian embryonic development, the primitive streak initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of a handful of transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereafter referred to as OSKM), albeit with low efficiency. Here we show that during OSKM-induced reprogramming towards pluripotency in human cells, intermediate cells transiently show gene expression profiles resembling mesendoderm, which is a major component of the primitive streak. Based on these findings, we discover that forkhead box H1 (FOXH1), a transcription factor required for anterior primitive streak specification during early development, significantly enhances the reprogramming efficiency of human fibroblasts by promoting their maturation, including mesenchymal to epithelial transition and the activation of late pluripotency markers. These results demonstrate that during the reprogramming process, human somatic cells go through a transient state that resembles mesendoderm.

Formulas providing adequate pantothenic acid, vitamin D, manganese, iron and vitamin A for infants fed with mother's milk (aged 6-11 months) according to the Japanese Dietary Reference Intakes prepared by the Ministry of Health, Labour and Welfare (2005 edition).

Weaning formulas served in hospitals and care facilities in Japan should conform to dietary reference intakes (DRIs). We examined whether the DRI for breastfed infants aged 6-11 months can be satisfied in dietary practice, with a particular focus on the fulfilment rates for vitamins, minerals, trace elements and electrolytes in weaning formulas containing energy and protein at levels either greater than or equal to the DRIs, as well as on the dietary profiles of weaning formulas to achieve the DRI for every nutrient. The results showed that no weaning formulas examined in this study fulfilled the DRI for pantothenic acid (5 mg), vitamin D (4 microg), manganese (1.2 mg) or iron (5.5 mg). Furthermore, their vitamin A content exceeded the DRI (350 microg RE). The discrepancy between the guidelines and actual dietary practice is probably because of the fact that the estimated reference values poorly reflect the actual dietary intake in the target population; for example, the pantothenic acid and manganese DRIs for breastfed infants aged 6-11 months were set based on the breast milk intake of younger infants (0-5 months) in combination with the breast milk contents. Our results suggest that dietary guidance for infants should include information to promote proper intakes of vitamins A and D, and iron by reducing the amount of vitamin A-rich foods and utilizing dietary vitamin D and iron supplements including government-approved specified health foods.