Cerebral oxygenation saturation in childhood: difference by age and comparison of two cerebral oximetry algorithms.

Few reports are available on the monitoring of regional cerebral oxygen saturation (rSO2) in pediatric patients undergoing non-cardiac surgical procedures. In addition, no study has examined the rSO2 levels in children of a broad age range. In this study, we aimed to assess and compare rSO2 levels in pediatric patients of different age groups undergoing non-cardiac surgery. We used two oximeters, tNIRS-1, which uses time-resolved spectroscopy, and conventional INVOS 5100C. Seventy-eight children-26 infants, 26 toddlers, and 26 schoolchildren-undergoing non-cardiac surgery were included. We investigated the differences in the rSO2 levels among the age groups and the correlation between the models and physiological factors influencing the rSO2 values. rSO2 measured by INVOS 5100C was significantly lower in infants than those in other patients. rSO2 measured by tNIRS-1 was higher in the toddler group than those in the other groups. The rSO2 values of tNIRS-1 and INVOS 5100C were moderately correlated (r = 0.41); however, those of INVOS 5100C were approximately 20% higher, and a ceiling effect was observed. The values in INVOS 5100C and tNIRS-1 were affected by blood pressure and the minimum alveolar concentration of sevoflurane, respectively. In pediatric patients undergoing non-cardiac surgery, rSO2 values differed across the three age groups, and the pattern of these differences varied between the two oximeters employing different algorithms. Further research must be conducted to clarify cerebral oxygenation in children.

Gap analysis between trainees' subjective competencies and the competencies expected by instructors in urology: A need assessment survey in Japan.

OBJECTIVE: According to the rapid progress in surgical techniques, a growing number of procedures should be learned during postgraduate training periods. This study aimed to clarify the current situation regarding urological surgical training and identify the perception gap between trainees' competency and the competency expected by instructors in Japan. METHODS: Regarding the 40 urological surgical procedures selected via the Delphi method, we collected data on previous caseloads, current subjective autonomy, and confidence for future skill acquisition from trainees (<15 post-graduate years [PGY]), and the competencies when trainees became attending doctors expected by instructors (>15 PGY), according to a 5-point Likert scale. In total, 174 urologists in Hokkaido Prefecture, Japan were enrolled in this study. RESULTS: The response rate was 96% (165/174). In a large proportion of the procedures, caseloads grew with accumulation of years of clinical practice. However, trainees had limited caseloads of robotic and reconstructive surgeries even after 15 PGY. Trainees showed low subjective competencies at present and low confidence for future skill acquisition in several procedures, such as open cystectomy, ureteroureterostomy, and ureterocystostomy, while instructors expected trainees to be able to perform these procedures independently when they became attending doctors. CONCLUSION: Trainees showed low subjective competencies and low confidence for future skill acquisition in several open and reconstructive procedures, while instructors considered that these procedures should be independently performable by attending doctors. We believe that knowledge of these perception gaps is helpful to develop a practical training program.

Decoupling power and type I error rate considerations when incorporating historical control data using a test-then-pool approach.

To accelerate a randomized controlled trial, historical control data may be used after ensuring little heterogeneity between the historical and current trials. The test-then-pool approach is a simple frequentist borrowing method that assesses the similarity between historical and current control data using a two-sided test. A limitation of the conventional test-then-pool method is the inability to control the type I error rate and power for the primary hypothesis separately and flexibly for heterogeneity between trials. This is because the two-sided test focuses on the absolute value of the mean difference between the historical and current controls. In this paper, we propose a new test-then-pool method that splits the two-sided hypothesis of the conventional method into two one-sided hypotheses. Testing each one-sided hypothesis with different significance levels allows for the separate control of the type I error rate and power for heterogeneity between trials. We also propose a significance-level selection approach based on the maximum type I error rate and the minimum power. The proposed method prevented a decrease in power even when there was heterogeneity between trials while controlling type I error at a maximum tolerable type I error rate larger than the targeted type I error rate. The application of depression trial data and hypothetical trial data further supported the usefulness of the proposed method.

Kidney donor age of 50 years or above is a risk factor for calcineurin inhibitor-induced nephrotoxicity.

INTRODUCTION: Calcineurin inhibitor (CNI)-induced nephrotoxicity (CNI-T) is a post-transplantation complication that leads to graft dysfunction. Older-donor kidney grafts may be susceptible to chronic CNI exposure because of long-term arteriolar damage. The primary aim of this study was to examine the CNI-T incidence and time-course changes in the graft function according to donor age. METHODS: We included 334 kidney transplant recipients. CNI-T was defined by Banff arteriolar hyaline thickening scores of ≥2 based on allograft protocol biopsy. Depending on donor age, participants were divided into the D > 70 (≥70 years), D60 (60-69 years), D50 (50-59 years), and D < 49: (≤49 years) groups. We investigated the extent to which CNI-T affected the transplanted kidney function. Patients who did not develop CNI-T during the study period were included in the non-CNI-T group; the remaining were grouped into the CNI-T group. RESULTS: The CNI-T incidence was higher in donors aged >50 years. Compared to D < 49, the CNI-T risk was 1.86 times higher in D50 and 2.9 times higher in D > 70. Furthermore, the CNI-T group exhibited a significantly lower graft function 10 years after transplantation. CONCLUSION: CNI-T incidence increases in donors aged ≥50 years and affects renal function after 10 years.

Differences of cerebral oxygen saturation in dialysis patients: a comparison of three principals of near infrared spectroscopy.

PURPOSE: It has been reported that cerebral oxygen saturation (rSO2) measured by near infrared spectroscopy is low in dialysis patients. We compared the rSO2 values of dialysis patients before living donor kidney transplantation and their donors as controls by using three spectroscopes that utilize different principals, the INVOS 5100C (spatially resolved spectroscopy), FORE-SIGHT ELITE (modified Beer-Lambert law) and tNIRS-1 (time-resolved spectroscopy). METHODS: Before induction of anesthesia, the sensors of one of the three spectroscopes were placed on the forehead and rSO2 values were recorded followed by the same measurement using the other two spectroscopes. The primary objective was to compare the rSO2 values of the dialysis patients and controls using the three spectroscopes by the unpaired t test. Then we compared the rSO2 values among the spectroscopes in both dialysis patients and controls by one-way ANOVA. Finally, we examined the relations between the rSO2 values and the physiological values by using the Pearson correlation coefficient. RESULTS: Fifteen pairs of dialysis patients and controls were studied. With the INVOS 5100 C, the values of the dialysis patients (59.7 ± 9.7% (mean ± standard deviation) were 13% lower than those of the controls (73.3 ± 6.9%) (P < 0.01). With the tNIRS-1, the values were 57.8 ± 4.8% in the dialysis patients and 63.3 ± 3.5% in the controls (P < 0.01). Almost no differences were observed with the FORE-SIGHT ELITE (71.6 ± 4.9% [dialysis patients] vs. 70.8 ± 4.3% [Controls]) (P = 0.62). Among the spectroscopes, the values were significantly different in both dialysis patients and controls. For the INVOS 5100C and tNIRS-1, correlation coefficients between rSO2 values and blood Hb and serum Alb were more than 0.5. CONCLUSIONS: The rSO2 values for comparisons between the dialysis patients and the controls were different according to differences of the principles of the near infrared spectroscopes. In the INVOS 5100C and tNIRS-1, rSO2 values may be related to blood Hb and serum Alb.

Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2014 to 2018 in Japan: A large-scale multicenter retrospective study.

AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. The aim of this study was to determine the recent prevalence and clinical characteristics of NAFLD in Japan. METHODS: This study initially included 410 061 retrospectively enrolled adults from the medical health checkup registry for metabolic syndrome, chronic kidney disease, and fatty liver in Japan (MIRACLE-J; UMIN-CTR no. UMIN000049419), who were evaluated between 2014 and 2018 at 13 health centers in Japan. Individuals consuming >20 g of alcohol/day or with chronic liver disease were excluded. Fatty liver was diagnosed by ultrasonography. The probability of NAFLD with advanced fibrosis was estimated based on the fibrosis-4 index and NAFLD fibrosis score. RESULTS: A total of 71 254 participants were included in the final analysis. The overall prevalence of NAFLD was 25.8%. There was a significant, twofold difference in NAFLD prevalence between men (37.4%) and women (18.1%). Nonalcoholic fatty liver disease prevalence increased linearly with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even in the absence of obesity. Among patients with NAFLD, 14% had diabetes mellitus, 31% had hypertension, and 48% had dyslipidemia. The estimated prevalence of NAFLD with advanced fibrosis was 1.7% and 1.0% according to the fibrosis-4 index and NAFLD fibrosis score, respectively. CONCLUSIONS: The prevalence of NAFLD was approximately one-quarter of the general population in Japan. There was a linear relationship between NAFLD prevalence and various metabolic parameters, even in nonobese participants. The prevalence of NAFLD with advanced fibrosis was estimated to be 1%-2%.

Preoperative mechanical bowel preparation using conventional versus hyperosmolar polyethylene glycol-electrolyte lavage solution before laparoscopic resection for colorectal cancer (TLUMP test): a phase III, multicenter randomized controlled non-inferiority trial.

BACKGROUND: A hyperosmolar ascorbic acid-enriched polyethylene glycol-electrolyte (ASC-PEG) lavage solution ensures excellent bowel preparation before colonoscopy; however, no study has demonstrated the efficacy of this lavage solution before surgery. This study aimed to establish the non-inferiority of ASC-PEG to the standard polyethylene glycol-electrolyte solution (PEG-ELS) in patients undergoing laparoscopic resection for colorectal cancer. METHODS: This was a prospective, single-blind, multicenter, randomized, controlled, non-inferiority clinical trial. Overall, 188 patients scheduled for laparoscopic colorectal resection for single colorectal adenocarcinomas were randomly assigned to undergo preparation with different PEG solutions between August 2017 and April 2020 at four hospitals in Japan. Participants received ASC-PEG (Group A) or PEG-ELS (Group B) preoperatively. The primary endpoint was the ratio of successful bowel preparations using the modified Aronchick scale, defined as "excellent" or "good." RESULTS: After exclusion, 86 and 87 patients in Groups A and B, respectively, completed the study, and their data were analyzed. ASC-PEG was not inferior to PEG-ELS in terms of effective bowel preparation prior to laparoscopic colorectal resection (0.93 vs. 0.92; 95% confidence interval, - 0.078 to 0.099, p = 0.007). The total volume of cleansing solution intake was lower in Group A than in Group B (1757.0 vs. 1970.1 mL). Two and three severe postoperative adverse events occurred in Groups A and B, respectively. Patient tolerance of the two solutions was almost equal. CONCLUSIONS: ASC-PEG is effective for preoperative bowel preparation in patients undergoing laparoscopic resection for colorectal cancer and is non-inferior to PEG-ELS.

Long-term risk of a fatty liver in liver donors.

Aim: Approximately 30 years have passed since the first experience of living donor liver transplantation. The time to evaluate the long-term safety of living donors has been fulfilled. Meanwhile, nonalcoholic fatty liver disease is increasingly common and a critical problem. The aim of this study was to evaluate the safety of living donor, focusing on fatty liver postdonation hepatectomy. Methods: Living donors (n = 212, 1997-2019) were evaluated by computed tomography (CT) at >1-year postdonation. A liver to spleen (L/S) ratio of <1.1 was defined as fatty liver. Results: Among 212 living liver donors, 30 (14.2%) detected fatty liver at 5.3 ± 4.2 years postdonation. The cumulative incidence rates of fatty liver were 3.1%, 12.1%, 22.1%, and 27.7% at 2, 5, 10, and 15 years postdonation, respectively. Of 30 subjects who developed fatty liver, 18 (60%) displayed a severe steatosis (L/S ratio <0.9). Five (16.7%) had a prior history of excessive alcohol abuse. More than 30% developed metabolic syndrome including obesity, hyperlipidemia, and diabetes. Although six (20%) had a Fib-4 index of >1.3, which included a case with a Fib-4 index of >2.67, no significant increased Fib-4 index was observed in the subjects with fatty liver as compared to those without fatty liver (p = 0.66). The independent predictive risk factors for developing fatty liver were male sex, pediatric recipient, and higher body mass index (>25) at donation. Conclusion: Living donors with risk factors for developing fatty liver should be carefully followed-up for the prevention and management of metabolic syndrome.

The comparison of postoperative analgesic requirements between modified thoracoabdominal nerve block through perichondrial approach versus wound infiltration analgesia in patients undergoing gynecological laparoscopic surgery: a retrospective, exploratory study.

INTRODUCTION: Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has been introduced as a novel trunk block. To date, studies comparing its clinical advantages with those of existing local anesthetic techniques are scarce. We aimed to compare the analgesic efficacy of M-TAPA to that of wound infiltration analgesia (WIA) in patients who underwent gynecological laparoscopic surgeries. METHODS: We studied medical records from January 2020 to July 2021 at Hokkaido University Hospital. The primary outcome was the number of analgesic requirements in the first 24 h postoperatively. Secondary outcomes were the time until the first analgesic requirement and adverse events regarding local anesthetic techniques. To address confounding, a regression model was used. RESULTS: Data from 90 of 231 patients were analyzed (M-TAPA group, n = 40; WIA group, n = 50). For the primary outcome, means and 95% confidence intervals for each group and between-group differences were as follows: 2.25 (1.74, 2.76), 2.28 (1.81, 2.75), and -0.03 (-0.72, 0.66), respectively. Adjusted mean difference was 0.39 (-0.32, 1.11). There were no significant differences in means between groups, with or without adjustment for covariates (p = 0.93, 0.28). Furthermore, no significant difference was detected in the time until the first analgesic requirement and adverse events related to local anesthesia. CONCLUSION: Our results demonstrate that M-TAPA did not reduce postoperative analgesic requirements compared to WIA. In a future clinical trial, sufficient visceral pain control may be required to evaluate the effectiveness of M-TAPA over WIA in patients undergoing laparoscopic gynecological surgery.

Change in cerebral circulation during the induction of anesthesia with remimazolam.

PURPOSE: Remimazolam is a new ultra-short-acting benzodiazepine with unknown effects on cerebral circulation. We measured total cerebral hemoglobin concentrations, which reflect cerebral blood volume (CBV), and cerebral oxygen saturation, using time-domain near-infrared spectroscopy, which can measure the absolute values of cerebral hemoglobin concentrations. We also measured cerebral blood flow velocity (CBFV) in the middle cerebral artery using transcranial Doppler as an indicator of cerebral blood flow (CBF). We did so to examine the effect of remimazolam on cerebral circulation in humans, as assessed CBV, CBF, and cerebral oxygen saturation. METHODS: This was a prospective, observational study. Fifteen patients without serious complications scheduled for general anesthesia were recruited. We measured total cerebral hemoglobin concentrations, CBFV, and cerebral oxygen saturation throughout the anesthetic induction course with remimazolam. RESULTS: Total cerebral hemoglobin concentrations did not change during the process (p = 0.51). In contrast, the mean CBFV was reduced by 11% (significant, p = 0.04). The drop in mean blood pressure following the induction of anesthesia was 17%; however, it was within the range of cerebrovascular autoregulation. Moreover, cerebral oxygen saturation increased by 4% (statistically significant, p < 0.01). CONCLUSIONS: We found that anesthetic induction with remimazolam did not alter CBV and reduced CBF in uncomplicated patients.

Stimulation of the mitochondrial calcium uniporter mitigates chronic heart failure-associated ventricular arrhythmia in mice.

BACKGROUND: An aberrant increase in the diastolic calcium concentration ([Ca2+]i) level is a hallmark of heart failure (HF) and the cause of delayed afterdepolarization and ventricular arrhythmia (VA). Although mitochondria play a role in regulating [Ca2+]i, whether they can compensate for the [Ca2+]i abnormality in ventricular myocytes is unknown. OBJECTIVE: The purpose of this study was to investigate whether enhanced Ca2+ uptake of mitochondria may compensate for an abnormal increase in the [Ca2+]i of ventricular myocytes in HF to effectively mitigate VA. METHODS: We used a HF mouse model in which myocardial infarction was induced by permanent left anterior descending coronary artery ligation. The mitochondrial Ca2+ uniporter was stimulated by kaempferol. Ca2+ dynamics and membrane potential were measured using an epifluorescence microscope, a confocal microscope, and the perforated patch-clamp technique. VA was induced in Langendorff-perfused hearts, and hemodynamic parameters were measured using a microtip transducer catheter. RESULTS: Protein expression of the mitochondrial Ca2+ uniporter, as assessed by its subunit expression, did not change between HF and sham mice. Treatment of cardiomyocytes with kaempferol, isolated from HF mice 28 days after coronary ligation, reduced the appearance of aberrant diastolic [Ca2+]i waves and sparks and spontaneous action potentials. Kaempferol effectively reduced VA occurring in Langendorff-perfused hearts. Intravenous administration of kaempferol did not markedly affect left ventricular hemodynamic parameters. CONCLUSION: The effects of kaempferol in HF of mice implied that mitochondria may have the potential to compensate for abnormal [Ca2+]i. Mechanisms involved in mitochondrial Ca2+ uptake may provide novel targets for treatment of HF-associated VA.

The renoprotective effect of once-weekly GLP-1 receptor agonist dulaglutide on progression of nephropathy in Japanese patients with type 2 diabetes and moderate to severe chronic kidney disease (JDDM67).

AIMS/INTRODUCTION: Few studies have investigated the renoprotective effect of glucagon-like peptide-1 (GLP-1) receptor in patients with chronic kidney disease (CKD). This study evaluated the effect of dulaglutide 0.75 mg on renal function in Japanese patients with type 2 diabetes and CKD stage 3 to 4. MATERIALS AND METHODS: Dulaglutide (group A) and non-dulaglutide (group B) were compared using data collected from a computerized diabetes care database. For group B, propensity score weighting based on propensity scores was performed. Evaluation items were a change from baseline in hemoglobin A1c (HbA1c), body weight, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), for 3 years. RESULTS: In total, the data obtained from 255 patients (125 and 130 patients for group A and B, respectively) were analyzed. Propensity score-adjusted patient background characteristics (group A vs B) were age 70.8 vs 69.4 years, body weight 70.2 vs 72.9 kg, body mass index 27.3 vs 28.1 kg/m2 , HbA1c 8.4 vs 8.5%, eGFR 47.9 vs 47.7 mL/min/1.73 m2 , and UACR 218 vs 251 mg/gCr. Although there were no statistically significant differences in the change from baseline between groups A and B at most time points in eGFR, a statistically significant eGFR decline in group B was observed in slope analysis for 3 years. This renoprotective effect was marked in patients with macro-albuminuria and/or concomitant SGLT2 inhibitor use. CONCLUSIONS: Dulaglutide slowed the eGFR decline in patients with type 2 diabetes and CKD stage 3 to 4.

Phase II Study of Ramucirumab Plus Irinotecan Combination Therapy as Second-Line Treatment in Patients with Advanced Gastric Cancer: HGCSG1603.

BACKGROUND: Ramucirumab is a human IgG1 monoclonal vascular endothelial growth factor receptor-2 antibody that inhibits tumor cell growth and affects the tumor cell microenvironment. We assessed the efficacy and safety of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with previously treated advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric cancer refractory or intolerant to primary chemotherapy were included. Ramucirumab 8 mg/kg plus irinotecan 150 mg/m2 combination therapy was administered every 2 weeks. The primary endpoint was progression-free survival rate at 6 months and secondary endpoints were overall survival, progression-free survival, response rate, safety, and dose intensity for each drug. RESULTS: Thirty-five patients were enrolled between January 2018 and September 2019. The progression-free survival rate at 6 months was 26.5% [95%CI, 13.2%-41.8%, P = .1353)]. Median progression-free and overall survivals were 4.2 months (95%CI, 2.5-5.4 months) and 9.6 months (95%CI, 6.4-16.6 months), respectively. The overall response rate was 25.9% (95%CI, 11.1-36.3%) and disease control rate was 85.2% (95%CI, 66.3-95.8%). Grade ≥3 adverse events that occurred in >10% of patients included neutropenia, leucopenia, anemia, anorexia, and febrile neutropenia. No death or new safety signals with a causal relation to the study treatment were observed. CONCLUSION: Although the primary endpoint was not achieved statistically, combination therapy of ramucirumab plus irinotecan showed anticancer activity and a manageable safety profile for second-line treatment of patients with advanced gastric cancer.

Usefulness of Aerobic Exercise for Home Blood Pressure Control in Patients with Diabetes: Randomized Crossover Trial.

Hypertension usually coexists with diabetes mellitus and significantly increases the risk of macrovascular complications. Blood pressure measured at home, especially nocturnal blood pressure, is particularly important because it is more strongly associated with target organ damage than clinical blood pressure measurements. Regular moderate aerobic exercise has been shown to have anti-hypertensive effects. This study aimed to investigate the effects of aerobic exercise on home blood pressure in patients with diabetes. This randomized crossover trial was based on outpatient treatment at a university hospital. In this randomized crossover trial, 124 patients with type 2 diabetes were randomly assigned to two groups over 56 days: an exercise preceding group (exercise intervention for 28 days and then no exercise intervention for the following 28 days) and an exercise lagging group (no exercise intervention for 28 days and then exercise intervention for the following 28 days). The associations between the nocturnal blood pressure and exercise intervention were assessed accordingly. A decrease in blood pressure was observed in the morning and evening, at 2 a.m. and 3 a.m. after exercise intervention; however, there was no significant difference between groups. Moderate exercise was not effective in lowering nocturnal blood pressure in this study.

The effect of local injection of tranexamic acid into peri-articular tissue versus drain clamping in total knee arthroplasty: a randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) is used as a synthetic anti-fibrinolytic agent for total knee arthroplasty (TKA) to reduce postoperative bleeding. Though the effects on bleeding reduction of several methods of administering TXA have been demonstrated, the optimal method remains controversial. Recently, the hemostatic effect of periarticular local injection of TXA during TKA was reported. Although this method can be expected to suppress postoperative bleeding without placing a drain, its hemostatic effect has not yet been assessed in comparison with local injection and other methods of administering TXA. The aim of this randomized, prospective study was to assess the efficacy of local injection of TXA during TKA. METHODS: To confirm the effect of the local injection of TXA, drain clamping was set as the control. The subjects included a prospective series of 109 patients randomly divided into 2 groups: the local injection (group L) and the drain clamping (group D). The main outcome measure was postoperative bleeding. Secondary outcomes included pain, physical measurements, and laboratory findings. RESULTS: The calculated total blood loss (CTBL) in groups L and D was nearly equal and did not show the non-inferiority of group L to group D (883 ± 248 vs. 841 ± 257 ml, P = .564). Drained blood loss was significantly higher in group L than in group D (395 ± 130 vs 276 ± 78.8 ml, P < .0001). There was no significant difference in hidden blood loss between the groups (488 ± 269 vs 565 ± 261 ml, P = .131). The other laboratory findings and physical measurements were identical between the groups. CONCLUSIONS: Although CTBL in group L did not show non-inferiority to group D, the local injection of TXA was considered to be superior for suppressing bleeding considering the risk of the adverse effects of using a drain. TRIAL REGISTRATION: This was a randomized, prospective study registered with UMIN Clinical Trials Registry (Registration number: UMIN000036146, date of disclosure: 10/3/2019).

Association Between Vitamin A Intake and Disease Severity in Early-Onset Heterotopic Ossification of the Posterior Longitudinal Ligament of the Spine.

STUDY DESIGN: A sex- and age-matched case-control study and a cross-sectional study. OBJECTIVE: In our previous study, patients with early-onset (<50 years of age) ossification of the posterior longitudinal ligament (OPLL) had distinct features such as morbid obesity, a high prevalence of lifestyle-related diseases, and diffuse ossified lesions mainly affecting the thoracic spine. Our goals were to determine whether early-onset OPLL patients have unbalanced dietary habits and to identify nutritional factors associated with OPLL exacerbation. METHODS: In Study 1, the simple brief-type self-administered diet history questionnaire (BDHQ) was used to compare nutrient intake levels of early-onset OPLL patients (n = 13) with those of sex- and age-matched non-OPLL controls (n = 39) or with those of common OPLL (onset age ≥ 50 years, n = 62). In Study 2, serological validation was conducted for thoracic OPLL patients (n = 77) and non-OPLL controls (n = 101) in a nationwide multicenter study in Japan. RESULTS: The BDHQ showed that the early-onset OPLL patients had significantly lower intakes of vitamins A and B6 than non-OPLL controls. These results were validated by lower serum vitamins A and B6 levels in the early-onset thoracic OPLL patients. The severity of OPLL negatively correlated with serum vitamin A levels in male early-onset OPLL patients. The multiple regression analysis revealed that the severity of thoracic OPLL had an association with onset age and serum vitamin A level. CONCLUSIONS: Vitamin A deficiency resulting from unbalanced dietary habits is associated with exacerbation of male early-onset OPLL.

Elevated serum CYFRA 21-1 level as a diagnostic marker for thymic carcinoma.

BACKGROUND: No useful tumor markers have been identified for the diagnosis of thymic carcinomas. Serum cytokeratin 19 fragment, measured using the CYFRA 21-1 immunoassay, is used as a tumor marker for squamous cell carcinomas in various malignant tumors. Here, we evaluated the value of CYFRA 21-1 in diagnosing thymic carcinoma. METHODS: We retrospectively reviewed 94 patients with pathological diagnoses of thymic carcinoma or thymoma (32 and 62 patients, respectively) who were referred to our departments between January 2000 and March 2019. Primary outcomes included tumor marker levels and their diagnostic accuracy. RESULTS: Patients with thymic carcinoma were significantly more likely to be male (thymic carcinoma, 68.8%; thymoma, 40.3%; p = 0.02), have an advanced TNM stage (p < 0.01), and a significantly higher CYFRA 21-1 level than those with thymoma (thymic carcinoma: median = 4.2 ng/ml; interquartile range [IQR] = 2.1-6.1 ng/ml vs. thymoma: median = 1.2 ng/ml; IQR = 0.9-1.7 ng/ml; p < 0.01). Receiver operating characteristic curves demonstrated that the area under the curve for CYFRA 21-1 to distinguish thymic carcinoma from thymoma was 0.86 (95% confidence interval [CI]: 0.74-0.93; cutoff = 2.7 ng/ml; sensitivity = 68.8%; specificity = 95.2%). Multivariable analysis demonstrated that CYFRA 21-1 (odds ratio = 25.6; 95% CI: 4.6-141.6; p < 0.01) was an independent predictor for thymic carcinoma after adjusting for TNM stage. CONCLUSIONS: Serum CYFRA 21-1 level may help in diagnosing thymic carcinoma.

Development and validation of a prediction model based on the organ-based metabolic tumor volume on FDG-PET in patients with differentiated thyroid carcinoma.

BACKGROUND: Although patients with differentiated thyroid cancer (DTC) generally have a good prognosis, patients with a large metabolic tumor volume (MTV) on FDG-PET may experience poor clinical courses. We measured organ-based MTVs and tested its prognostic performance in comparison to conventional MTV (cMTV). METHODS: We retrospectively analyzed the cases of 280 patients who received their first I-131 therapy in 2003-2014 at our hospital and showed an FDG-avid metastatic lesion. We randomly divided the patients into training (n = 190) and validation (n = 90) datasets. We classified the MTVs as MTVneck-node, MTVdistant-node, MTVlung, MTVbone, and MTVother-organs and tested with/without dichotomization vis-à-vis overall survival (OS). Based on the estimated weighting coefficients of the organ-based MTVs, we propose a new index: the adjusted whole-body MTV (aMTV). Using the validation dataset, we compared the aMTV with cMTV for predicting OS. RESULTS: In a univariate analysis, MTVdistant-node and MTVother-organs were more strongly correlated with the OS than the dichotomized forms, whereas the dichotomized forms of MTVneck-node, MTVlung, and MTVbone were more strongly correlated with OS than the continuous variables. The aMTV was thus expressed as 0.69 × dic(MTVneck-node) + 0.02 × MTVdistant-node + 1.05 × dic(MTVlung) + 1.58 × dic(MTVbone) + 0.01 × MTVother-organs, where dic(x) represents 0 or 1 based on the optimized cut-off. In the model evaluation using the validation group, aMTV was a significant predictor of OS with a higher c-index (0.7676) than cMTV (0.7218). CONCLUSION: In DTC patients with FDG-avid metastasis before I-131 therapy, all organ-based MTVs were significant predictors of prognosis. As the aMTV outperformed the cMTV for predicting prognoses, we recommend measuring the MTV on an organ basis.

A novel strategy for SARS-CoV-2 mass screening with quantitative antigen testing of saliva: a diagnostic accuracy study.

BACKGROUND: Quantitative RT-PCR (RT-qPCR) of nasopharyngeal swab (NPS) samples for SARS-CoV-2 detection requires medical personnel and is time consuming, and thus is poorly suited to mass screening. In June, 2020, a chemiluminescent enzyme immunoassay (CLEIA; Lumipulse G SARS-CoV-2 Ag kit, Fujirebio, Tokyo, Japan) was developed that can detect SARS-CoV-2 nucleoproteins in NPS or saliva samples within 35 min. In this study, we assessed the utility of CLEIA in mass SARS-CoV-2 screening. METHODS: We did a diagnostic accuracy study to develop a mass-screening strategy for salivary detection of SARS-CoV-2 by CLEIA, enrolling hospitalised patients with clinically confirmed COVID-19, close contacts identified at community health centres, and asymptomatic international arrivals at two airports, all based in Japan. All test participants were enrolled consecutively. We assessed the diagnostic accuracy of CLEIA compared with RT-qPCR, estimated according to concordance (Kendall's coefficient of concordance, W), and sensitivity (probability of CLEIA positivity given RT-qPCR positivity) and specificity (probability of CLEIA negativity given RT-qPCR negativity) for different antigen concentration cutoffs (0·19 pg/mL, 0·67 pg/mL, and 4·00 pg/mL; with samples considered positive if the antigen concentration was equal to or more than the cutoff and negative if it was less than the cutoff). We also assessed a two-step testing strategy post hoc with CLEIA as an initial test, using separate antigen cutoff values for test negativity and positivity from the predefined cutoff values. The proportion of intermediate results requiring secondary RT-qPCR was then quantified assuming prevalence values of RT-qPCR positivity in the overall tested population of 10%, 30%, and 50%. FINDINGS: Self-collected saliva was obtained from 2056 participants between June 12 and Aug 6, 2020. Results of CLEIA and RT-qPCR were concordant in 2020 (98·2%) samples (Kendall's W=0·99). Test sensitivity was 85·4% (76 of 89 positive samples; 90% credible interval [CrI] 78·0-90·3) at the cutoff of 0·19 pg/mL; 76·4% (68 of 89; 68·2-82·8) at the cutoff of 0·67 pg/mL; and 52·8% (47 of 89; 44·1-61·3) at the cutoff of 4·0 pg/mL. Test specificity was 91·3% (1796 of 1967 negative samples; 90% CrI 90·2-92·3) at the cutoff of 0·19 pg/mL, 99·2% (1952 of 1967; 98·8-99·5) at the cutoff of 0·67 pg/mL, and 100·0% (1967 of 1967; 99·8-100·0) at the cutoff of 4·00 pg/mL. Using a two-step testing strategy with a CLEIA negativity cutoff of 0·19 pg/mL (to maximise sensitivity) and a CLEIA positivity cutoff of 4·00 pg/mL (to maximise specificity), the proportions of indeterminate results (ie, samples requiring secondary RT-qPCR) would be approximately 11% assuming a prevalence of RT-qPCR positivity of 10%, 16% assuming a prevalence of RT-qPCR positivity of 30%, and 21% assuming a prevalence of RT-qPCR positivity of 50%. INTERPRETATION: CLEIA testing of self-collected saliva is simple and provides results quickly, and is thus suitable for mass testing. To improve accuracy, we propose a two-step screening strategy with an initial CLEIA test followed by confirmatory RT-qPCR for intermediate concentrations, varying positive and negative thresholds depending on local prevalence. Implementation of this strategy has expedited sample processing at Japanese airports since July, 2020, and might apply to other large-scale mass screening initiatives. FUNDING: Ministry of Health, Labour and Welfare, Japan.

Acute Oral Calcium Suppresses Food Intake Through Enhanced Peptide-YY Secretion Mediated by the Calcium-Sensing Receptor in Rats.

BACKGROUND: Dietary calcium has been proposed to reduce appetite in human studies. Postprandial satiety is mainly controlled by gut hormones. However, the effect of calcium on appetite and the role of gut hormones remain unclear. OBJECTIVES: We examined whether oral administration of calcium reduces food intake in rats and investigated the underlying mechanism. METHODS: Male Sprague Dawley rats (8-12 wk old) were used after an overnight fastifffng. In a series of 2 trials with 1-wk interval between challenges, food intake was measured 0.5-24 h after oral gavage of a vehicle (saline containing 1.5% carboxymethyl cellulose) as the control treatment, or the vehicle containing various calcium compounds [calcium chloride (CaCl2), calcium carbonate, calcium lactate, in a random order] at 150 mg calcium/kg dose. A conditional taste aversion test was conducted. In separate experiments, plasma calcium and gut hormone concentrations were measured 15 or 30 min after oral administration of the calcium compounds. In anesthetized rats, portal peptide-YY (PYY) concentrations were measured after intraluminal administration of a liquid meal with or without additional calcium. RESULTS: Oral CaCl2 reduced food intake acutely (30 min, ∼20%, P < 0.05) compared with control rats, without taste aversion. Plasma PYY concentration was higher (100%, P < 0.05) in CaCl2-preloaded rats than in control rats, 15 min after administration. In anesthetized rats, luminal meal + CaCl2 induced a 4-fold higher increase in plasma PYY than the control treatment did. Oral administration of a calcium-sensing receptor (CaSR) agonist suppressed food intake (∼30%, P < 0.05), but CaCl2 and CaSR agonist did not suppress food intake under treatment with a PYY receptor antagonist. Furthermore, the CaSR antagonist attenuated the effect of CaCl2 on food intake. CONCLUSIONS: CaCl2 suppresses food intake partly by increasing CaSR-mediated PYY secretion in rats. Our findings could at least partially explain the satiating effect of calcium.