Association of ADC of hyperintense lesions on FLAIR images with TERT promoter mutation status in glioblastoma IDH wild type.

Background: Although mutations in telomerase reverse transcriptase (TERT) promoter (TERTp) are the most common alterations in glioblastoma (GBM), predicting TERTp mutation status by preoperative imaging is difficult. We determined whether tumour-surrounding hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) were superior to those of contrast-enhanced lesions (CELs) in assessing TERTp mutation status using magnetic resonance imaging (MRI). Methods: This retrospective study included 114 consecutive patients with primary isocitrate dehydrogenase (IDH)-wild-type GBM. The apparent diffusion coefficient (ADC) and volume of CELs and FLAIR hyperintense lesions (FHLs) were determined, and the correlation between MRI features and TERTp mutation status was analyzed. In a subset of cases, FHLs were histopathologically analyzed to determine the correlation between tumor cell density and ADC. Results: TERTp mutations were present in 77 (67.5%) patients. The minimum ADC of FHLs was significantly lower in the TERTp-mutant group than in the TERTp-wild-type group (mean, 958.9 × 10-3 and 1092.1 × 10-3 mm2/s, respectively, P < 0.01). However, other MRI features, such as CEL and FHL volumes, minimum ADC of CELs, and FHL/CEL ratio, were not significantly different between the two groups. Histopathologic analysis indicated high tumor cell density in FHLs with low ADC. Conclusion: The ADC of FHLs was significantly lower in IDH-wild-type GBM with TERTp mutations, suggesting that determining the ADC of FHLs on preoperative MRI might be helpful in predicting TERTp mutation status and surgical planning.

The MDM2-p53 Axis Represents a Therapeutic Vulnerability Unique to Glioma Stem Cells.

The prevention of tumor recurrence by the successful targeting of glioma stem cells endowed with a tumor-initiating capacity is deemed the key to the long-term survival of glioblastoma patients. Glioma stem cells are characterized by their marked therapeutic resistance; however, recent evidence suggests that they have unique vulnerabilities that may be therapeutically targeted. We investigated MDM2 expression levels in glioma stem cells and their non-stem cell counterparts and the effects of the genetic and pharmacological inhibition of MDM2 on the viability of these cells as well as downstream molecular pathways. The results obtained showed that MDM2 expression was substantially higher in glioma stem cells than in their non-stem cell counterparts and also that the inhibition of MDM2, either genetically or pharmacologically, induced a more pronounced activation of the p53 pathway and apoptotic cell death in the former than in the latter. Specifically, the inhibition of MDM2 caused a p53-dependent increase in the expression of BAX and PUMA and a decrease in the expression of survivin, both of which significantly contributed to the apoptotic death of glioma stem cells. The present study identified the MDM2-p53 axis as a novel therapeutic vulnerability, or an Achilles' heel, which is unique to glioma stem cells. Our results, which suggest that non-stem, bulk tumor cells are less sensitive to MDM2 inhibitors, may help guide the selection of glioblastoma patients suitable for MDM2 inhibitor therapy.

Antagonizing MDM2 Overexpression Induced by MDM4 Inhibitor CEP-1347 Effectively Reactivates Wild-Type p53 in Malignant Brain Tumor Cells.

The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study using CEP-1347, an inhibitor of MDM4 protein expression. The effects of CEP-1347, the genetic and/or pharmacological inhibition of MDM2, and their combination on the p53 pathway in malignant brain tumor cell lines expressing wild-type p53 were investigated by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 alone or in combination with MDM2 on inhibition were examined by dye exclusion and/or colony formation assays. The treatment of malignant brain tumor cell lines with CEP-1347 markedly increased MDM2 protein expression, while blocking CEP-1347-induced MDM2 overexpression by genetic knockdown augmented the effects of CEP-1347 on the p53 pathway and cell growth. Blocking the MDM2-p53 interaction using the small molecule MDM2 inhibitor RG7112, but not MDM2 knockdown, reduced MDM4 expression. Consequently, RG7112 effectively cooperated with CEP-1347 to reduce MDM4 expression, activate the p53 pathway, and inhibit cell growth. The present results suggest the combination of CEP-1347-induced MDM2 overexpression with the selective inhibition of MDM2's interaction with p53, while preserving its ability to inhibit MDM4 expression, as a novel and rational strategy to effectively reactivate p53 in wild-type p53 cancer cells.

The Novel MDM4 Inhibitor CEP-1347 Activates the p53 Pathway and Blocks Malignant Meningioma Growth In Vitro and In Vivo.

A significant proportion of meningiomas are clinically aggressive, but there is currently no effective chemotherapy for meningiomas. An increasing number of studies have been conducted to develop targeted therapies, yet none have focused on the p53 pathway as a potential target. In this study, we aimed to determine the in vitro and in vivo effects of CEP-1347, a small-molecule inhibitor of MDM4 with known safety in humans. The effects of CEP-1347 and MDM4 knockdown on the p53 pathway in human meningioma cell lines with and without p53 mutation were examined by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 were examined in vitro and in a mouse xenograft model of meningioma. In vitro, CEP-1347 at clinically relevant concentrations inhibited MDM4 expression, activated the p53 pathway in malignant meningioma cells with wild-type p53, and exhibited preferential growth inhibitory effects on cells expressing wild-type p53, which was mostly mimicked by MDM4 knockdown. CEP-1347 effectively inhibited the growth of malignant meningioma xenografts at a dose that was far lower than the maximum dose that could be safely given to humans. Our findings suggest targeting the p53 pathway with CEP-1347 represents a novel and viable approach to treating aggressive meningiomas.

Preoperative Risk Factors in Patients With Pancreatic Cancer.

Background: Pancreatic cancer is gastrointestinal cancer with a poor prognosis. Although surgical techniques and chemotherapy have improved treatment outcomes, the 5-year survival rate for pancreatic cancer is less than 10%. In addition, resection of pancreatic cancer is highly invasive and is associated with high rates of postoperative complications and hospital mortality. The Japanese Pancreatic Association states that preoperative body composition assessment may predict postoperative complications. However, although impaired physical function is also a risk factor, few studies have examined it in combination with body composition. We examined preoperative nutritional status and physical function as risk factors for postoperative complications in pancreatic cancer patients. Methods: Fifty-nine patients with pancreatic cancer who underwent surgical treatment and were discharged alive from January 1, 2018, to March 31, 2021, at the Japanese Red Cross Medical Center. This retrospective study was conducted using electronic medical records and a database of departments. Body composition and physical function were evaluated before and after surgery, and the risk factors between patients with and without complications were compared. Results: Fifty-nine patients were analyzed: 14 and 45 patients in the uncomplicated and complicated groups, respectively. The major complications were pancreatic fistulas (33%) and infections (22%). There were significant differences in: age, 74.0 (44 - 88) (P = 0.02); walking speed, 0.93 m/s (0.3 - 2.2) (P = 0.01); and fat mass, 16.50 kg (4.7 - 46.2) (P = 0.02), in the patients with complications. On Multivariable logistic regression analysis, age (odds ratio: 2.28; confidence interval (CI): 1.3400 - 569.00; P = 0.03), preoperative fat mass (odds ratio: 2.28; CI: 1.4900 - 168.00; P = 0.02), and walking speed (odds ratio: 0.119; CI: 0.0134 - 1.07; P = 0.05) were identified as risk factors. Walking speed (odds ratio: 0.119; CI: 0.0134 - 1.07; P = 0.05) was the risk factor that was extracted. Conclusions: Older age, more preoperative fat mass, and decreased walking speed were possible risk factors for postoperative complications.

Domatinostat Targets the FOXM1-Survivin Axis to Reduce the Viability of Ovarian Cancer Cells Alone and in Combination with Chemotherapeutic Agents.

The deregulation of the FOXM1 transcription factor is a key molecular alteration in ovarian cancer, contributing to the development and progression of ovarian cancer via activation of the target genes. As such, FOXM1 is a highly attractive therapeutic target in the treatment of ovarian cancer, but there has been no clinically tested FOXM1 inhibitor to date. We investigated in this study the effects of domatinostat, a class I-selective HDAC inhibitor currently in the clinical stage of development as a cancer therapeutic, on the expression of FOXM1 and viability of ovarian cancer cells. Cell viability, as well as protein and mRNA expression of FOXM1 and its transcriptional target survivin, was examined after domatinostat treatment of TOV21G and SKOV3 ovarian cancer cell lines in the absence or presence of cisplatin and paclitaxel. The effect of FOXM1 knockdown on survivin expression and those of genetic and pharmacological inhibition of survivin alone or in combination with the chemotherapeutic agents on cell viability were also examined. Domatinostat reduced the protein and mRNA expression of FOXM1 and survivin and also the viability of ovarian cancer cells alone and in combination with cisplatin or paclitaxel at clinically relevant concentrations. Knockdown experiments showed survivin expression was dependent on FOXM1 in ovarian cancer cells. Survivin inhibition was sufficient to reduce the viability of ovarian cancer cells alone and in combination with the chemotherapeutic agents. Our findings suggest that domatinostat, which effectively targets the FOXM1-survivin axis required for the viability of ovarian cancer cells, is a promising option for the treatment of ovarian cancer.

Differences in Analgesia Methods for Open Gastrointestinal Surgery Are Not Associated With Initial Postoperative Ambulation.

Background: A characteristic of modern medical care is the reduction in the length of hospital stay, and several facilities across Japan are working towards this goal. The presence of postoperative pain is correlated with the number of days to hospital discharge. Therefore, this study investigated the relationship between the analgesic methods used in clinical practice and the initial ambulation of postoperative laparotomy patients with severe postoperative worked incisional pain to enable better analgesic management in the future. Methods: This retrospective study collected information from the medical records of 117 patients who underwent laparotomy between December 1, 2019, and October 13, 2020, at the Department of Gastroenterology of the International University of Health and Welfare Mita Hospital. Based on the failure or success of the ambulation process, the patients were divided into the delayed and successful groups, respectively. Results: In the delayed group, patient-controlled epidural analgesia (PCEA) was used in 32 patients, intravenous patient-controlled analgesia (IV-PCA) was used in two patients, continuous worked incisional infiltration anesthesia was used in one patient, and transvenous acetaminophen was used in one patient for postoperative analgesia. In the successful group, PCEA was used in 66 patients, IV-PCA was used in 11 patients, continuous worked incisional infiltration anesthesia was used in three patients, and acetaminophen administered intravenously at patient's request was used in one patient (P = 0.094). Conclusions: No significant differences were observed between different postoperative analgesia methods, suggesting that there may be no association between postoperative ambulation and the postoperative analgesia method.

Predictors of Catheter-Related Bladder Discomfort After Surgery: A Literature Review.

Background: Indwelling bladder catheters are routinely used in clinical practice. Patients may experience postoperative indwelling catheter-related bladder discomfort (CRBD). This study aimed to perform a literature review to identify predictors of postoperative CRBD. Methods: We searched PubMed for relevant articles published between 2000 and 2020 using the search items "CRBD", "catheter-related bladder discomfort", and "prediction". Additionally, we searched for articles that matched the research objectives from the references of the extracted articles. We included only prospective observational studies involving human participants and excluded interventional studies, observational studies that did not report sample sizes, or observational studies that did not research on predictors of CRBD. We narrowed our search to the keyword "prediction" and found five references. We selected five studies that met the objectives of the study as the target literature. Results: Using the keywords "CRBD" and "catheter-related bladder discomfort", we identified 69 published articles. The results were narrowed down by the keyword "prediction", and five studies that recruited 1,147 patients remained. The predictors of CRBD can be divided into four factors: 1) patient factors; 2) surgical factors; 3) anesthesia factors; and 4) device and insertion technique factors. Conclusion: Our study suggests that patients with predictors of CRBD should be closely monitored to reduce postoperative patient suffering, and their quality of life should be improved after anesthesia.

Givinostat Inhibition of Sp1-dependent MGMT Expression Sensitizes Glioma Stem Cells to Temozolomide.

BACKGROUND/AIM: Givinostat is a pan-histone deacetylase (HDAC) inhibitor that has demonstrated excellent tolerability as well as efficacy in patients with polycythemia vera. Accumulating in vitro and in vivo evidence suggests givinostat is also promising as a therapeutic agent targeting glioma stem cells (GSCs), the cancer stem cells of glioblastoma (GBM) considered responsible for its intractable nature. However, it remains to be shown how givinostat impacts the therapeutic effects of temozolomide, a DNA-alkylating agent and the key component of GBM treatment given not only during postoperative radiotherapy but also thereafter as maintenance chemotherapy. MATERIALS AND METHODS: The effects of givinostat and knockdown of O6-methylguanine-DNA methyltransferase (MGMT) or Sp1 on the mRNA and protein expression of relevant genes in human GSC lines were examined by RT-PCR and western blot analyses. The dye exclusion method was used to evaluate cell viability. RESULTS: Givinostat enhanced the cytotoxic activity of temozolomide in GSC lines expressing MGMT, in which the MGMT expression was shown to contribute to their temozolomide resistance. Givinostat inhibited MGMT expression in GSCs and, in parallel, the expression of Sp1, a transcription factor involved in the control of MGMT promoter activity. Knockdown experiments demonstrated Sp1 expression was indeed required for MGMT expression in GSCs. CONCLUSION: Givinostat, in addition to its own cytotoxic activity, sensitizes GSCs to temozolomide by inhibiting Sp1-dependent MGMT expression in GSCs. Combining givinostat with temozolomide could therefore be a rational therapeutic strategy to effectively eliminate GSCs and thus help overcome the therapy resistance of GBM.

Usefulness of Serum Soluble Interleukin-2 Receptor Levels for Differentiating between PCNSL and SCNSL.

Serum soluble interleukin-2 receptor (sIL-2R) is a practical tumor marker that is elevated in hematogenous tumors. The purpose of this study was to determine the usefulness of serum sIL-2R for differentiating among malignant brain tumors, including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL). This study retrospectively investigated the sIL-2R levels in 130 patients with various types of malignant brain tumors, including PCNSL patients (n = 48) and SCNSL (n = 8); metastatic brain tumors (MTs, n = 16); and glioblastoma (GBM, n = 58). The median sIL-2R level (U/mL) of the PCNSL, SCNSL, MTs, and GBM groups were 489.7, 1024.8, 413.3, and 332.7 respectively. The sIL-2R level was significantly higher in the SCNSL group than in the PCNSL or other groups. The area under the ROC curve generated from the sIL-2R level was 0.826 (sensitivity: 0.875, specificity: 0.667, cutoff value: 521 U/mL) for differentiating SCNSL from PCNSL and 0.685 (sensitivity: 0.667, specificity: 0.707, cutoff value: 342 U/mL) for differentiating PCNSL from GBM. Measurement of sIL-2R level was convenient and useful to differentiate between SCNSL and PCSNL, both of which demand different treatment strategies.

CEP-1347 Dually Targets MDM4 and PKC to Activate p53 and Inhibit the Growth of Uveal Melanoma Cells.

Uveal melanoma (UM) is among the most common primary intraocular neoplasms in adults, with limited therapeutic options for advanced/metastatic disease. Since UM is characterized by infrequent p53 mutation coupled with the overexpression of MDM4, a major negative regulator of p53, we aimed to investigate in this study the effects on UM cells of CEP-1347, a novel MDM4 inhibitor with a known safety profile in humans. We also examined the impact of CEP-1347 on the protein kinase C (PKC) pathway, known to play a pivotal role in UM cell growth. High-grade UM cell lines were used to analyze the effects of genetic and pharmacological inhibition of MDM4 and PKC, respectively, as well as those of CEP-1347 treatment, on p53 expression and cell viability. The results showed that, at its clinically relevant concentrations, CEP-1347 reduced not only MDM4 expression but also PKC activity, activated the p53 pathway, and effectively inhibited the growth of UM cells. Importantly, whereas inhibition of either MDM4 expression or PKC activity alone failed to efficiently activate p53 and inhibit cell growth, inhibition of both resulted in effective activation of p53 and inhibition of cell growth. These data suggest that there exists a hitherto unrecognized interaction between MDM4 and PKC to inactivate the p53-dependent growth control in UM cells. CEP-1347, which dually targets MDM4 and PKC, could therefore be a promising therapeutic candidate in the treatment of UM.

Changes in vascular supply pattern associated with growth of nonfunctioning pituitary adenomas.

Background: The vascular supply to nonfunctioning pituitary adenomas (NFPAs) differs compared with that of the anterior lobe of the normal pituitary gland. In this study, we aimed to identify feeding arteries and flow dynamics using 3.0 T magnetic resonance imaging (MRI) in NFPAs. Methods: We divided 77 cases of NFPA into three groups according to the time-intensity curve (TIC) pattern by dynamic MRI. We also investigated the presence of feeder arteries as a flow void signal on T2-weighted imaging (T2WI). Results: According to the TIC, 39 cases demonstrated an ascending pattern, 10 cases demonstrated a descending pattern, and 28 cases demonstrated a monophasic pattern. Tumor size in the ascending group was larger compared with the descending group (P = 0.0036). Flow void signals were identified in 51 of 77 cases (66.2%) on T2WI. Tumor size was larger in tumors with a flow void signal compared with those without (P < 0.0001). Flow void signals were more frequently observed in the group of ascending pattern compared with the group of monophasic and descending pattern (P = 0.032 and P = 0.003, respectively). Particularly on the caudal side, the difference between the ascending group and the monophasic and descending groups was remarkable (P = 0.0035 and P < 0.0001, respectively). Conclusion: We successfully evaluated the blood supply pattern by the TIC analysis and identified flow voids using 3.0 T MRI. Blood supply pattern was significantly associated with NFPA size. These results suggested that NFPA hemodynamics changes during tumor growth.

Perspectives on Collaboration between Physicians and Nurse Practitioners in Japan: A Cross-Sectional Study.

BACKGROUND: Nurse practitioners (NPs) are known as effective healthcare providers worldwide. In Japan, nurse practitioner adoption is considered to be in a shaky period. Although nurse practitioners were introduced approximately 10 years ago at the initiative of educational institutions in Japan, the full extent of this trend is not known. Therefore, we have clarified the whole picture of nurse practitioners from two directions: the perception of nurse practitioners in Japan and the perception of physicians who work with nurse practitioners. This will inform discussions regarding the recruitment of nurse practitioners at the national level in Japan. METHODS: From 18 June to 24 July 2021, we administered a nationwide cross-sectional survey of NPs and physicians working in the same clinical settings as NPs in Japan. The domains of the survey included "scope and content of work", "perceptions of NPs' clinical practice", and "individual clinical practice characteristics". The survey was distributed and collected digitally. RESULTS: The total number of respondents to the survey was 281, including 169 NPs and 112 physicians; the percentage of NPs who responded was 50.5%. The number of valid responses was 164 NPs and 111 physicians, for a total of 275 respondents. Approximately 60% of NPs are concentrated in Tokyo, the capital of Japan, and the three prefectures adjacent to Tokyo. They also worked fewer hours per week, cared for fewer patients per day, and earned less money than physicians. More physicians than NPs indicated that "more NPs would improve the quality of care". A total of 90.1% of physicians and 82.3% of NPs agreed that "Nurse practitioners should practice to the full extent of their education and training," and 73.9% of physicians and 81.7% of NPs agreed that "Nurse practitioners' scope of practice should be uniformly defined at a national level". CONCLUSIONS: This study clarified the present working conditions of NPs from NPs' and physicians' perspectives in Japanese contexts. Japanese NPs may be able to work effectively in collaboration with physicians. Therefore, the implementation of NPs in Japanese medical conditions should be discussed further for better healthcare.

CEP-1347 Targets MDM4 Protein Expression to Activate p53 and Inhibit the Growth of Glioma Cells.

BACKGROUND/AIM: The development of pharmacological inhibitors targeting negative regulators of p53, such as murine double minute (MDM) 2 and, more recently, MDM4, has been actively pursued as a potential strategy to treat cancers with wild-type p53. We previously showed that CEP-1347, a small molecule kinase inhibitor originally developed for the treatment of Parkinson's disease, suppressed MDM4 expression and activated wild-type p53 in retinoblastoma cells. However, it remains unknown whether CEP-1347 acts as an MDM4 inhibitor and as such activates p53 in other types of human cancer cells. MATERIALS AND METHODS: The effects of CEP-1347 and MDM4 knockdown on the mRNA and protein expression of components of the p53 pathway, including MDM4, in human glioma cell lines with and without p53 mutation were examined by RT-PCR and western blot analyses. Trypan blue dye exclusion was used to examine the effect of CEP-1347 on cell growth. RESULTS: CEP-1347 decreased the expression of MDM4, increase that of p53, and activated the p53 pathway in glioma cells with wild-type p53. Knockdown-mediated inhibition of MDM4 expression in a glioma cell line with wild-type p53 that overexpresses MDM4 resulted in increased p53 expression and activation of the p53 pathway. CEP-1347 preferentially inhibited the growth of glioma cells with wild-type p53 without showing toxicity to normal cells at clinically relevant concentrations. CONCLUSION: Our findings suggest CEP-1347 is a novel inhibitor of MDM4 protein expression and as such activates p53 to inhibit the growth of cancer cells with wild-type p53, including retinoblastoma and glioblastoma.

Inhibition of the Phospholipase Cε-c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties.

Glioma stem cells (GSCs), the cancer stem cells of glioblastoma multiforme (GBM), contribute to the malignancy of GBM due to their resistance to therapy and tumorigenic potential; therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. The molecular mechanisms maintaining GSCs need to be elucidated in more detail for the development of GSC-targeted therapy. In comparison with patient-derived GSCs and their differentiated counterparts, we herein demonstrated for the first time that phospholipase C (PLC)ε was highly expressed in GSCs, in contrast to other PLC isoforms. A broad-spectrum PLC inhibitor suppressed the viability of GSCs, but not their stemness. Nevertheless, the knockdown of PLCε suppressed the survival of GSCs and induced cell death. The stem cell capacity of residual viable cells was also suppressed. Moreover, the survival of mice that were transplanted with PLCε knockdown-GSCs was longer than the control group. PLCε maintained the stemness of GSCs via the activation of JNK. The present study demonstrated for the first time that PLCε plays a critical role in maintaining the survival, stemness, and tumor initiation capacity of GSCs. Our study suggested that PLCε is a promising anti-GSC therapeutic target.

HDAC Class I Inhibitor Domatinostat Preferentially Targets Glioma Stem Cells over Their Differentiated Progeny.

Cancer stem cells (CSCs) are in general characterized by higher resistance to cell death and cancer therapies than non-stem differentiated cancer cells. However, we and others have recently revealed using glioma stem cells (GSCs) as a model that, unexpectedly, CSCs have specific vulnerabilities that make them more sensitive to certain drugs compared with their differentiated counterparts. We aimed in this study to discover novel drugs targeting such Achilles' heels of GSCs as anti-GSC drug candidates to be used for the treatment of glioblastoma, the most therapy-resistant form of brain tumors. Here we report that domatinostat (4SC-202), a class I HDAC inhibitor, is one such candidate. At concentrations where it showed no or minimal growth inhibitory effect on differentiated GSCs and normal cells, domatinostat effectively inhibited the growth of GSCs mainly by inducing apoptosis. Furthermore, GSCs that survived domatinostat treatment lost their self-renewal capacity. These results suggested that domatinostat is a unique drug that selectively eliminates GSCs not only physically by inducing cell death but also functionally by inhibiting their self-renewal. Our findings also imply that class I HDACs and/or LSD1, another target of domatinostat, may possibly have a specific role in the maintenance of GSCs and therefore could be an attractive target in the development of anti-GSC therapies.

Potential eating disorder exhibited with daytime functional vulnerabilities associated with sleep problems in Japanese adolescents: A cross-sectional study.

OBJECTIVES: Eating disorders (ED) are serious psychiatric disorders that affect individuals, especially adolescents. It has been suggested that nonclinical ED-like characteristics are related to sleep problems. We conducted a survey of Japanese adolescents to investigate this claim. METHOD: In this cross-sectional study, 398 adolescents aged 12-18 years responded to a self-administered questionnaire survey. We used the Eating Attitudes Test-26 (EAT-26) and the Athens Insomnia Scale (AIS) to measure potential ED and sleep problems, respectively. RESULTS: Adolescents with potential ED had significantly higher daytime functional vulnerability potentially associated with sleep problems than those without ED. In particular, problems with a sense of well-being and physical and mental functioning during the day were significant. In contrast, no significant associations were found between potential ED and sleep initiation, awakenings during the night, early morning awakening, total sleep duration, or overall quality of sleep. Finally, nocturnal and daytime sleep scores were significantly associated with dieting, bulimia, and oral control EAT-26 subscores. DISCUSSION: Participants with possible ED experienced problems related to well-being and mental and physical functioning, which are indicators of daytime functional vulnerability potentially associated with sleep problems. Further, adolescents with more severe ED characteristics are more likely to have a higher degree of daytime psychological vulnerability potentially attributable to sleep problems. The study suggested that professionals treating adolescent mental health issues need an approach that comprehensively integrates both sleep problems and potential ED.

A Literature Review of Factors Related to Postoperative Sore Throat.

Postoperative sore throat can occur as a complication in patients who have undergone surgery under general anesthesia. The incidence of postoperative sore throat ranges from 12.1% to 70%, and its effects include damage to the epithelium and mucosal cells caused by airway securement, damage to the vocal cords, congestion, blood clots, and factors such as an inappropriately large tube, cuff shape, cuff pressure, and airway securement. Notably, there are individual differences in pain thresholds, and the sensation of pain is affected by mental states, such as anxiety, and varies from person to person. Therefore, we conducted a literature review using PubMed to clarify patient factors related to the development of postoperative sore throat. The extracted keywords were "postoperative sore throat," "anesthesia," and "patient factors." We found 16 articles that met our search criteria. We expanded the search period and retrieved 19 cases from 1990 to 2020. We also included references that were judged to be closely related to the list of citations of the retrieved references. The study designs included were randomized controlled trials, clinical trials, meta-analyses, reviews, and systematic reviews. The results showed that female sex, smoking, and age were the most common patient factors. However, we could not find any literature that studied the relationship between postoperative sore throat and mental states such as anxiety.

Optimal Skeletal Muscle Mass Index Cut-Off Values for Presarcopenia Evaluated by Computed Tomography against Dual-Energy X-ray Absorptiometry in Patients with Chronic Liver Disease.

Although dual-energy X-ray absorptiometry (DXA) and body impedance analysis are commonly used to measure skeletal muscle mass (SMM), a computed tomography (CT) scan is preferred in clinical practice. We aimed to propose the cut-off values of skeletal muscle mass index (SMI) calculated using CT scans, using DXA as the reference method. We retrospectively assessed 589 patients with chronic liver disease. The SMI was assessed using appendicular SMM by DXA and total muscle area at the level of the third lumbar vertebra (L3) calculated by CT. The cut-off value was determined with reference to the Asian Working Group for Sarcopenia criteria. DXA identified 251 (42.6%) patients as having presarcopenia. In men, the cut-off value of SMI for presarcopenia was determined to be 45.471 cm2/m2, with an area under the curve (AUC) of 0.863 (95% confidence interval (CI): 0.823 to 0.903), and in women, this value was determined to be 35.170 cm2/m2, with an AUC of 0.846 (95% CI: 0.800 to 0.892). Cohen's kappa coefficient was 0.575 (95% CI: 0.485-0.665) in men and 0.539 (95% CI: 0.438-0.639) in women.

Effect of levocarnitine administration in patients with chronic liver disease.

L-carnitine administration was reported to improve sarcopenia in patients with cirrhosis. However, the amount of evidence from previous studies is not sufficient. The present study aimed to clarify the effect of levocarnitine (L-carnitine) administration on body composition in patients with chronic liver disease (CLD). In the present study, 85 patients with L-carnitine administration and 87 control patients were enrolled and divided them into two groups, the L-carnitine administration group (LAG, n=44) and the without L-carnitine administration (controls, n=44) group, by using propensity score matching for age, sex, body mass index (BMI) and serum albumin. Δ skeletal muscle mass index (SMI)/year, Δ intramuscular adipose tissue content (IMAC)/year and Δ bone mineral density (BMD)/year were examined during L-carnitine administration. Each parameter was measured by computed tomography (CT) or dual-energy X-ray absorptiometry. The median age overall was 69 years (IQR, 64.0, 75.0); 36 were men and 52 were women. The median SMI was 37.4 cm2/m2 (IQR, 34.01, 44.34). The initial CT scans showed similar median values of SMI for the two groups [37.74 (34.17, 43.58) and 37.16 (33.83, 44.34), P=0.67]. However, the median ΔSMI/year for the LAG and controls were 0.95% (-3.07, 6.10) and -2.34% (-5.34, 0.53), respectively (P=0.003). The median Δ whole body BMD/year for the LAG and controls were -0.24% (-1.20, 0.91) and -1.04% (-2.16, 0.47), respectively (P=0.038). The median ΔIMAC/year and Δ lumbar spine BMD were not significantly different between the LAG and controls. L-carnitine administration may prevent the loss of skeletal muscle mass and BMD; therefore, it may be used as a new treatment option for osteoporosis and sarcopenia in patients with CLD.