Functional reorganization of brain regions supporting artificial grammar learning across the first half year of life.

Pre-babbling infants can track nonadjacent dependencies (NADs) in the auditory domain. While this forms a crucial prerequisite for language acquisition, the neurodevelopmental origins of this ability remain unknown. We applied functional near-infrared spectroscopy in neonates and 6- to 7-month-old infants to investigate the neural substrate supporting NAD learning and detection using tone sequences in an artificial grammar learning paradigm. Detection of NADs was indicated by left prefrontal activation in neonates while by left supramarginal gyrus (SMG), superior temporal gyrus (STG), and inferior frontal gyrus activation in 6- to 7-month-olds. Functional connectivity analyses further indicated that the neonate activation pattern during the test phase benefited from a brain network consisting of prefrontal regions, left SMG and STG during the rest and learning phases. These findings suggest a left-hemispheric learning-related functional brain network may emerge at birth and serve as the foundation for the later engagement of these regions for NAD detection, thus, providing a neural basis for language acquisition.

CONUT score as a predictor for anamorelin efficacy in patients with cancer cachexia receiving chemotherapy.

BACKGROUND: Anamorelin is expected to improve cancer cachexia by increasing lean body mass (LBM) due to increased appetite and protein synthesis. However, the effect of anamorelin on cancer cachexia in real-world practice is unclear. The purpose of this study was to evaluate the efficacy and safety of anamorelin and to identify predictors of efficacy on treatment with anamorelin. METHODS: We retrospectively analyzed data from patients with cancer cachexia treated with chemotherapy between May 2021 and August 2022. Efficacy of anamorelin was evaluated using LBM, with "12-week sustained effective response" to anamorelin treatment defined as maintenance or an increase in LBM for 12 weeks. We examined factors associated with "12-week sustained effective response" to anamorelin treatment using a multivariable logistic model that included controlling nutritional status (CONUT) score, an objective assessment of nutritional disorders, and the modified Glasgow prognostic score (mGPS), which scores the cachexia status of cancer patients. To assess patient subjective quality of life (QOL) changes related to eating after starting anamorelin treatment, we used a questionnaire (QOL-ACD appetite-related items: Q8, 9, 11). Adverse events were evaluated in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. RESULTS: On analysis of data from 40 patients, 23 patients showed a 12-week sustained effective response to anamorelin (57.5%). At 12 weeks, LBM significantly increased by 1.63 ± 3.73 kg (mean ± SD). Multivariable logistic analysis revealed that a low CONUT score was significantly associated with "12-week sustained effective response" to anamorelin treatment (adjusted odds ratio: 13.5, 95% confidence intervals: 2.2-84.2, P = 0.004). QOL assessment showed a trend toward increased appetite and enjoyment of meals after anamorelin initiation. Five patients (12.5%) had an increase in HbA1c of more than 1.0% during the 12 weeks after the start of anamorelin. No patient had QT interval prolongation or grade 3 or higher hepatic transaminase elevation. CONCLUSION: Anamorelin may maintain or increase LBM with tolerable safety in patients with cancer cachexia undergoing chemotherapy. A low CONUT score, despite meeting criteria for cancer cachexia, is suggested as a predictor for the efficacy of anamorelin, indicating that patients with a low CONUT score may benefit from early introduction of anamorelin.

Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

The emerging emetogenicity of trifluridine/tipiracil (TAS­102) from patient self-reporting: a multicenter, prospective, observational study.

BACKGROUND: Trifluridine/tipiracil (TAS-102) is an oral anticancer drug with adequate efficacy in unresectable colorectal cancer, but frequently also induces chemotherapy-induced nausea and vomiting (CINV). To investigate the occurrence of CINV and antiemetic therapy in patients with colorectal cancer treated with TAS-102 (JASCC-CINV 2001). METHODS: We conducted a multicenter, prospective, observational study in patients with colorectal cancer who received TAS-102 without dose reduction for the first time. Primary endpoint was the incidence of vomiting during the overall period. Secondary endpoints were the incidence of nausea, significant nausea, anorexia, other adverse events (constipation, diarrhea, insomnia, fatigue, dysgeusia) and patient satisfaction. Patient diaries were used for primary and secondary endpoints. All adverse events were subjectively assessed using PRO-CTCAE ver 1.0. and CTCAE ver 5.0. RESULTS: Data from 100 of the 119 enrolled patients were analyzed. The incidence of vomiting, nausea, and significant nausea was 13%, 67%, and 36%, respectively. The incidence of vomiting in patients with and without prophylactic antiemetic therapy were 20.8% and 10.5%, respectively. Prophylactic antiemetics were given to 24% of patients, of whom 70% received D2 antagonists. Multivariate Cox proportional hazards analysis showed that experience of CINV in previous treatment tended to be associated with vomiting (hazard ratio [HR]: 7.13, 95% confidence interval [CI]: 0.87-58.5, P = 0.07), whereas prophylactic antiemetic administration was not (HR: 1.61, 95 CI: 0.50-5.21, P = 0.43). With regard to patient satisfaction, the proportion of patients who were "very satisfied," "satisfied," "slightly satisfied" or "somewhat satisfied" was 81.8%. CONCLUSIONS: The low incidence of vomiting and high patient satisfaction suggest that TAS-102 does not require the use of uniform prophylactic antiemetic treatments. However, patients with the experience of CINV in previous treatment might require prophylactic antiemetic treatment.

Invasive pneumococcal disease caused by non-vaccine Streptococcus pneumoniae serotype 24B in an immunocompetent child.

Invasive pneumococcal disease typically occurs in immunocompromised patients, although some vaccine strains of Streptococcus pneumoniae have been reported to cause invasive pneumococcal disease in immunocompetent vaccine recipients. In this study, we presented a case of a 16-month-old immunocompetent patient with lung abscess and empyema caused by nonvaccine S. pneumoniae serotype 24B. A consolidation occupying the right upper lobe in the chest computed tomography results, as observed at presentation, changed to thick-walled cavitary lesions at the end of a month of intravenous antibiotics, and antibiotics were continued for a total of two months. To the best of our knowledge this is the first report that focuses on the risk of invasive pneumococcal disease caused by S. pneumoniae serotype 24B in an immunocompetent child.

Usefulness of an intraoperative flipped monitor in laparoscopic surgery with situs inversus totalis: a case report of laparoscopic-assisted ileocecal resection.

BACKGROUND: Situs inversus totalis (SIT) is a rare congenital condition that involves complete transposition (right to left reversal) of the visceral organs. Laparoscopic surgery can be challenging because of the mirror-image anatomy. We describe a surgical innovation in laparoscopic surgery for SIT. CASE PRESENTATION: A 41-year-old man with SIT was diagnosed with an appendiceal tumor and underwent laparoscopic-assisted ileocecal resection. Preoperatively, we evaluated anatomical variations using 3D-computed tomography and simulated mirror images by watching flipped videos of patients with normal anatomy undergoing similar operations. During the operation, port placement and the surgeons' standing positions were reversed. Additionally, two monitors were placed at the patient's head, with one monitor showing original images, and the other showing flipped images that looked the same as the normal anatomy. We checked the range of the mobilized region and important anatomical structures by watching the flipped monitor as needed. The patient's postoperative course was uneventful. CONCLUSIONS: Due to the complexities of laparoscopic surgery for SIT, preoperative preparation and surgical innovation are necessary for safe surgery. Several suggestions have been made to understand anatomical anomalies and improve operability; however, surgeons must focus on the mirror-image anatomy throughout the operation. Therefore, the use of intraoperative flipped monitor will be helpful for surgeons in reducing the risk of anatomical misidentification.

Catheter-associated urinary tract infection and urinary tract abnormalities in young children: A retrospective study.

INTRODUCTION: Studies investigating the role of urinary tract abnormalities in the development of catheter-associated urinary tract infections (CAUTI) in young children are limited. Thus, in the present study, we aimed to determine whether there is an association between CAUTI and urinary tract abnormalities. METHODS: We performed abdominal imaging studies on all patients aged <6 years with CAUTI admitted to the pediatric intensive care units (PICU) and high care unit (HCU) at Keio university or Fukuoka Children's Hospital from April 1, 2018 to July 31, 2022. Among 40 children who developed CAUTI, 13 (33 %) had abnormal urogenital images. Further, two case-control studies were conducted before and after propensity score matching, and the groups were compared using multivariable logistic regression models to analyze the effects of various factors on CAUTI development. RESULTS: In the multivariate logistic regression models, abnormal urogenital images (OR 5.30 [95 % CI, 2.40-11.7] and OR 3.44 [95 % CI, 1.16-9.93]) and duration of catheterization >10 days (OR 2.76 [95 % CI, 1.28-5.96] and OR 3.44 [95 % CI, 1.16-9.93]) were found to be significantly associated with development of CAUTI, both before (39 cases, 459 controls) and after propensity score matching (36 cases, 72 controls). Further, CAUTI in young children in the PICU or HCU was significantly associated with imaging abnormalities of the urinary tract. CONCLUSIONS: These results suggest that not only the presence of catheters, but also urinary tract malformations may contribute to the development of CAUTI in young children.

Technical outcomes of robotic-assisted surgery versus laparoscopic surgery for rectal tumors: a single-center safety and feasibility study.

PURPOSE: Robot-assisted surgery has a multi-joint function, which improves manipulation of the deep pelvic region and contributes significantly to perioperative safety. However, the superiority of robot-assisted surgery to laparoscopic surgery remains controversial. This study compared the short-term outcomes of laparoscopic and robot-assisted surgery for rectal tumors. METHODS: This single-center, retrospective study included 273 patients with rectal tumors who underwent surgery with anastomosis between 2017 and 2021. In total, 169 patients underwent laparoscopic surgery (Lap group), and 104 underwent robot-assisted surgery (Robot group). Postoperative complications were compared via propensity score matching based on inverse probability of treatment weighting (IPTW). RESULTS: The postoperative complication rates based on the Clavien-Dindo classification (Lap vs. Robot group) were as follows: grade ≥ II, 29.0% vs. 19.2%; grade ≥ III, 10.7% vs. 5.8%; anastomotic leakage (AL), 6.5% vs. 4.8%; and urinary dysfunction (UD), 12.1% vs. 3.8%. After adjusting for the IPTW method, although AL rates did not differ significantly between groups, postoperative complications of both grade ≥ II (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.50-0.87, p < 0.01) and grade ≥ III (OR 0.29, 95% CI 0.16-0.53, p < 0.01) were significantly less frequent in the Robot group than in the Lap group. Furthermore, urinary dysfunction also tended to be less frequent in the Robot group than in the Lap group (OR 0.62, 95% CI 0.38-1.00; p = 0.05). CONCLUSION: Robot-assisted surgery for rectal tumors provides better short-term outcomes than laparoscopic surgery, supporting its use as a safer approach.

Prognostic impact of severe neutropenia in colorectal cancer patients treated with TAS-102 and bevacizumab, addressing immortal-time bias.

BACKGROUND: Several studies have reported an association between severe neutropenia and long-term survival in patients treated with trifluridine-tipiracil (TAS-102). Because some of these studies failed to address immortality time bias, however, their findings should be interpreted with caution. Additionally, the association between severe neutropenia and survival in patients receiving TAS-102 in combination with bevacizumab (Bmab) remains unclear. PATIENTS AND METHODS: We conducted a single-center retrospective cohort study in patients with colorectal cancer who received Bmab + TAS-102. We compared overall survival (OS) between patients who developed grade ≥ 3 neutropenia during the treatment period and those who did not. To account for immortal time bias, we used two approaches, time-varying Cox regression and landmark analysis. RESULTS: Median OS was 15.3 months [95% CI: 14.1-NA] in patients with grade ≥ 3 neutropenia and 10.0 months [95% CI: 8.1-NA] in those without. In time-varying Cox regression, onset grade ≥ 3 neutropenia was significantly related to longer survival after adjustment for age and modified Glasgow Prognostic Score. Additionally, 30-, 60-, 90-, and 120-day landmark analysis showed that grade ≥ 3 neutropenia was associated with longer survival after adjustment for age and modified Glasgow Prognostic Score, with respective HRs of 0.30 [0.10-0.90], 0.65 [0.30-1.42], 0.39 [0.17-0.90], and 0.41 [0.18-0.95]. CONCLUSION: We identified an association between long-term survival and the development of severe neutropenia during the early cycle of Bmab + TAS-102 using an approach that addressed immortality time bias.

Clinicopathological prognostic characteristics and long­term outcomes of patients with breast cancer and collagen disorder in comparison to those without collagen disorder.

Collagen disorders are chronic autoimmune diseases with a complex clinical course; however, the risk of breast cancer in patients with collagen disorders remains unclear. The present study aimed to investigate long-term outcomes in women with breast cancer and collagen disorders. A total of 25 patients with breast cancer and collagen disorders who were treated between January 2004 and December 2011 were included. The clinicopathological factors, treatment, recurrence-free survival (RFS) and overall survival (OS) were reviewed. The mean age was 56.4±12.6 years, and 14, eight and three patients had cancer of clinical stages I, II and III, respectively. Regarding comorbid collagen disorders, 11 patients had rheumatoid arthritis, four had systemic lupus erythematosus, four had polymyositis/dermatomyositis, two had mixed connective tissue disease, two had Sjogren's syndrome, one had scleroderma and one had adult-onset Still's disease. The expression statuses of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) were HR(+), HER2(+) and HR(-)HER2(-) in 20 (80.0%), four (16.0%) and four (16.0%) patients, respectively. A total of 22 (84.0%) patients received steroids or immunosuppressive drugs for collagen disorders. The collagen disorder group had a higher mean Ki-67 labeling index than the control group (41.1 vs. 20.8%; P=0.007). After median observation periods of 103 and 114 months, the RFS and OS rates were lower in the collagen group than in the control group (64.5 and 80.7% vs. 85.3 and 94.3%, respectively; P<0.01). Patients with breast cancer and collagen disorders had relatively high Ki-67 expression, and relatively low RFS and OS rates. Thorough follow-up is necessary for patients with breast cancer who also have collagen disorders and high Ki-67 values.

Prognostic factors in patients with high-risk stage II colon cancer after curative resection: a post hoc analysis of the JFMC46-1201 trial.

PURPOSE: The goal of the current study was to identify prognostic factors for disease-free survival (DFS) and overall survival (OS) in high-risk stage II colon cancer. METHODS: The subjects were patients with histologically confirmed stage II colon cancer undergoing R0 resection who met at least one of the following criteria: T4, perforation/penetration, poorly differentiated adenocarcinoma, mucinous carcinoma, and < 12 examined lymph nodes. Patients self-selected surgery alone or a 6-month oral uracil and tegafur plus leucovorin (UFT/LV) regimen. Serum CEA mRNA at ≥ 24 h after surgery and < 2 weeks after registration was also examined as a potential prognostic factor for stage II colon cancer. This study is registered with UMIN-CTR (protocol ID: UMIN000007783). RESULTS: 1880 were included in the analysis to identify prognostic factors for DFS and OS in patients with high-risk stage II colon cancer. In multivariate analyses, gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and postoperative adjuvant chemotherapy (POAC) emerged as significant independent prognostic factors for DFS. Similarly, multivariate analysis showed that age, gender, depth of tumor invasion, perforation/penetration, extent of lymph node dissection, number of examined lymph nodes, and POAC were significant independent prognostic factors for OS. Univariate analyses showed no significant difference in DFS or OS for CEA mRNA-positive and mRNA-negative cases. CONCLUSION: This study showed that gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and lack of use of POAC were significant independent prognostic factors in stage II colon cancer.

Short-term outcomes associated with the use of a new powered circular stapler for rectal reconstructions: a retrospective study comparing it to manual circular staplers using inverse probability of treatment weight analysis.

BACKGROUND: The most common postoperative complication in malignant rectal surgery is anastomotic leakage (AL). AL after anterior or low anterior resection in rectal tumors is a fatal postoperative complication. Recently, the first automated suture circular stapler, which is expected to reduce the incidence of AL, (J&J). MATERIALS AND METHODS: This study included a total of 248 rectal tumor patients who underwent double stapler technique (DST) anastomotic procedures in the department of gastroenterological surgery /pediatric surgery at Gifu University School of Medicine from January 2017 to December 2021. The experience of a single institution utilizing the The Echelon circular™ stapler (ECP stapler:Manual VS Automatic) in rectal surgery cases was evaluated retrospectively from maintained database. RESULT: One hundred thirty-nine patients (58.4%) were performed by manual circular stapling, 99 patients (41.6%) by powerd circular stapling. Diverting stoma was performed in 45 cases (32.4%) by manual circular stapling, 42 patients (42.4%) by powerd circular stapling Postoperative complications were occurred clavien-dindo grade II or higher in 57 cases (23.9%) and grade III or higher in 20 cases (8.4%). Anastomotic leakage occurred in 14 patients (5.9%) within all grades. After IPTW, the variables of patient characteristics was SMD ≤ 0.2 (Table.3), and there was a significant difference in anastomotic leakage (Odds Ratio (OR), 0.57; 95% Confidence Interval(CI), 0.34-0.98; p = 0.041). In addition, there was no significant difference in postoperative complications in grade II or higher (OR, 0.88; 95%CI, 0.65-1.19; p = 0.417) and grade III or higher (OR, 0.46; 95%CI, 0.29-0.74; p = 0.001) were significantly remarkable lower in powered circular stapling group. CONCLUSION: In this IPTW comparison of patients undergoing rectal reconstructions, the ECP trial cohort had lower risks of several surgical complications AL and statistically signifcant lower rates of ileus/bowel obstruction, infection, and bleeding as Clavien-Dindo ≥ grade II and III as compared with for whom manual circular staplers were used.

Effectiveness of inactivated influenza and COVID-19 vaccines in hospitalized children in 2022/23 season in Japan - The first season of co-circulation of influenza and COVID-19.

We have analyzed the inactivated vaccine effectiveness (VE)for preventing influenza hospitalization by test-negative design in the 2022/23 season. This is the first season of co-circulation of influenza and COVID-19, and a unique period because all inpatients received COVID-19 screening. Among 536 children hospitalized with fever, none were positive for both influenza and SARS-CoV-2. The adjusted VE for preventing influenza A for all children, the 6-12-year-old group, and those with underlying diseases was 34 % (95 ％CI, -16 %-61 %, n = 474), 76 % (95 ％ CI, 21 %-92 %, n = 81), and 92 % (95 ％ CI, 30 %-99 %, n = 86), respectively. Only 1 out of 35 hospitalized cases with COVID-19, and 42 out of 429 controls, had been immunized with COVID-19 vaccine. This is the first report showing influenza VE by age group in children in this limited season. We still recommend the inactivated influenza vaccine for children based on the significant VE in subgroup analysis.

Postoperative reflux esophagitis in laparoscopic distal gastrectomy with Billroth-I reconstruction for gastric cancer: Nutritional effect and preoperative risk factors.

INTRODUCTION: Postoperative reflux esophagitis represents a major complication of laparoscopic distal gastrectomy (LDG) with Billroth-I reconstruction (LDGBI). This study aimed to evaluate the nutritional effect and preoperative risk factors of postoperative reflux esophagitis in patients undergoing LDGBI for gastric cancer. METHODS: We retrospectively analyzed data of patients with (reflux [+]) and without (reflux [-]) postoperative reflux esophagitis who underwent LDGBI in our institution. Patient backgrounds, surgical outcomes, and perioperative nutritional status were compared. Preoperative risk factors for postoperative reflux esophagitis were also evaluated. RESULTS: Between January 2009 and December 2016, 242 patients underwent LDG for gastric cancer. Of these, 218 underwent Billroth-I reconstruction. Seventy-three patients were excluded because of nutritional or oncological reasons. Finally, 23 patients were enrolled as the reflux (+) group and 122 as the reflux (-) group. Although the preoperative/postoperative bodyweight ratio and albumin and hemoglobin values plateaued beyond 6 months postoperatively in the reflux (-) group, these parameters continued to decrease beyond this time in the reflux (+) group. The mean ± SD bodyweight ratios at 3 years postoperatively were 82.83% ± 9.73% and 89.45% ± 8.04% for the reflux (+) and reflux (-) group, respectively (P = .0006). Multivariate analysis revealed that postoperative reflux esophagitis was associated with postoperative body weight loss. Another multivariate analysis revealed preoperative hiatal hernia as an independent predictive factor for postoperative reflux esophagitis. CONCLUSION: The risk of reflux esophagitis after LDGBI in patients with hiatal hernia should be considered when deciding therapeutic approaches for such patients.

The prevalence of thiamine deficiency among elderly nursing home residents: A cross-sectional study.

Background: Although thiamine deficiency (TD) can lead to Wernicke encephalopathy, the characteristics associated with TD in the elderly have not yet been clarified. We sought to clarify the frequency of TD among an institutionalized elderly population with a controlled dietary intake and to identify possible factors related to TD. Method: We undertook a cross-sectional study of residents in three nursing homes for the elderly as of June 2020. Blood thiamine concentrations were measured using a high-performance liquid chromatography method, with TD defined as a concentration of <21.3 ng/mL. Basic data (age, sex, height, weight, and BMI), dietary intake for the previous 3 weeks, degree of care (DOC), degree of independence in daily life for elderly with dementia (DIDLED), and comorbidities were analyzed using descriptive statistical methods. Results: The mean age (±SD) was 86.9 years (±8.29), with 84 residents (70.0%) being female. The DIDLED varied from total independence to long-term care level 5 (full assistance), with 89.2% suffering dementia. The mean whole blood thiamine value was 36.18 (±17.58) ng/ml, with TD confirmed in 7 (5.8%) of the 120 residents. All TD patients suffered from dementia. No TD was observed in patients with a near-normal food intake, and no related factors were observed among the other items. Conclusion: Reduced food intake may at increase the risk of TD and symptoms of TD may be overlooked in those displaying symptoms of dementia; thus, it is important for clinicians working with the elderly to remain aware of the potential for TD.

Investigation of Whole Blood Thiamine Concentration in Independently Ambulatory Residents of a Provincial Town in Japan: A Cross-Sectional Study.

Background Thiamine deficiency (TD) is an important public health problem in nutrition, occurring in 2-6% of the population in Europe and the US, whereas thiamine levels are reported to be significantly reduced by 36.6-40% in some populations of East Asia. However, there is little information available at present, regarding factors such as age, despite the continued aging of society. Further, studies such as those mentioned above have not yet been undertaken in Japan, the country in which population aging is most advanced. Objective To investigate TD in the Japanese community-dwelling individuals who are independently ambulatory. Methods We undertook an examination of TD in blood samples obtained from 270 citizens in a provincial town, aged 25-97 years, who were able to walk to the venue and provide informed consent for inclusion in this research and of whom 8.9% had a history of cancer. We summarized the demographic characteristics of the subjects. The whole-blood thiamine concentrations were measured using the high-performance liquid chromatography method. A value of 21.3 ng/ml or less was taken as low and a borderline value was set as less than 28 ng/ml. Results The mean (±SD) whole blood thiamine concentration was 47.6 ± 8.7 ng/ml. No TD was observed to exist participating in this study, with no subjects even showing show borderline values. Further, there was no significant difference in thiamine level between those aged 65 or older and those aged less than 65. Conclusions No cases of TD were observed among the subjects in this study, nor was the concentration of thiamine found to be related to age. It is possible that the frequency of TD might be very low in citizens who have a certain level of activity. In the future, it is necessary to expand the prevalence of TD to a wider range of subjects.

Naldemedine-induced opioid withdrawal with restlessness as the predominant symptom in a palliative care setting.

OBJECTIVES: Opioid analgesics play a central role in cancer pain treatment; however, it has been reported that opioid-induced constipation (OIC) develops in 80% of patients using opioid analgesics and leads to a decrease in quality of life. Naldemedine improves constipation without affecting the analgesic action of opioid analgesics via peripheral µ-opioid receptors. METHODS: We report a terminally ill cancer patient who was diagnosed with opioid withdrawal syndrome (OWS) based on symptoms centered around restlessness and sweating that developed 43 days after administration of naldemedine for OIC. RESULTS: The patient was a 78-year-old woman who was diagnosed with stage IVB uterine sarcoma in October, 1 year prior to her visit to our clinic,  and underwent chemotherapy after surgery, but the disease became progressive. Thereafter, metastasis to the fourth thoracic vertebrae (Th4) was identified, and loxoprofen and acetaminophen were started for pain at the metastatic site. Oxycodone hydrochloride hydrate 10 mg/day was additionally administered on postoperative day 11, followed by naldemedine 0.2 mg/day for OIC. On the 43rd day after administration, the patient began to wander the hospital ward in a wheelchair and became noticeably restless. OWS due to naldemedine administration was suspected, and naldemedine was discontinued. The symptoms improved 7 days later, and no similar symptoms were observed thereafter. SIGNIFICANCE OF RESULTS: Patients receiving palliative care often exhibit psychiatric symptoms such as anxiety and depression, but OWS due to naldemedine should also be considered as a potential cause.

[Drug Administration for Childhood Neurological Disorders].

In this review, we summarized drug administration strategies for childhood diseases, such as childhood epilepsy and attention-deficit hyperactivity disorder (ADHD). Therapeutic drug monitoring is recommended for most antiepileptic drugs; however, dosage of these in the clinical setting is usually based solely on body weight or age. Other factors to be considered are dosage form and taste; these are particularly important in infants and toddlers as they affect the adherence to a given medicine and may impose a limitation on drug administration. In addition, we should be cautious about such side-effects as the effect on appetite. Special attention should be paid if there is a history of long-time treatment during childhood, because appetite loss or stimulation might have had a substantial negative impact on growth during childhood. We also briefly summarized newly introduced drug therapies for spinal muscular atrophy. These include gene therapy and exon-skipping drugs, which increase the amount of functioning SMN2 protein in skeletal muscles. In particular, the focus of this treatment is on the age of the patient and copy number of the SMN2 gene, both of which are key parameters.