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Purpose: This study aimed to clarify the incidence, therapeutic modality, and prognosis of acute acalculous cholecystitis and to reveal its optimal treatment strategy., Methods: As a project study of the Japanese Society for Abdominal Emergency Medicine, we performed a questionnaire survey of demographic data and perioperative outcomes of acute acalculous cholecystitis treated between January 2018 and December 2020 from 42 institutions., Results: In this study, 432 patients of acute acalculous cholecystitis, which accounts for 7.04% of acute cholecystitis, were collected. According to the Tokyo guidelines severity grade, 167 (38.6%), 202 (46.8%), and 63 (14.6%) cases were classified as Grade I, II, and III, respectively. A total of 11 (2.5%) patients died and myocardial infarction/congestive heart failure was the only independent risk factor for in-hospital death. Cholecystectomy, especially the laparoscopic approach, had more preferable outcomes compared to their counterparts. The Tokyo guidelines flow charts were useful for Grade I and II severity, but in the cases with Grade III, upfront cholecystectomy could be suitable in some patients., Conclusions: The proportions of severity grade and mortality of acute acalculous cholecystitis were found to be similar to those of acute cholecystitis, and laparoscopic cholecystectomy is recommended as an effective treatment option. (UMIN000047631)., (© 2023 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

The 2020 summer Olympic and Paralympic Games in Tokyo were postponed to July-September 2021 due to the coronavirus disease 2019 (COVID-19) pandemic. While COVID-19 has emerged as a monumental health threat for mass gathering events, heat illness must be acknowledged as a potentially large health threat for maintaining health services. We examined the number of COVID-19 admissions and the Tokyo rule for emergency medical care, in Tokyo, from March to September 2020, and investigated the weekly number of emergency transportations due to heat illness and weekly averages of the daily maximum Wet Bulb Globe Temperature (WBGT) in Tokyo in the summer (2016-2020). The peak of emergency transportations due to heat illness overlapped the resurgence of COVID-19 in 2020, and an increase of heat illness patients and WBGT has been observed. Respect for robust science is critical for the decision-making process of mass gathering events during the pandemic, and science-based countermeasures and implementations for COVID-19 will be warranted. Without urgent reconsiderations and sufficient countermeasures, the double burden of COVID-19 and heat-related illnesses in Tokyo will overwhelm the healthcare provision system, and maintaining essential health services will be challenging during the 2021 summer Olympic and Paralympic Games.

Background: Preoperative anxiety and postoperative delirium affect both short- and long-term prognoses in patients with cancer; therefore, these conditions require early prevention and treatment. However, no standard preventive or therapeutic methods have been established for them. Yokukansan, a Japanese herbal medicine for the treatment of insomnia and anxiety, causes relatively few adverse drug reactions and effectively improves the behavioral and psychological symptoms of dementia. Thus, it is expected to be useful for treating and/or preventing perioperative psychiatric symptoms in patients with cancer. The objective of this study is to clarify the therapeutic effect of Yokukansan for preoperative anxiety and its preventive effect on postoperative delirium in cancer patients, as well as to confirm its safety profile., Methods: This study is a randomized, double-blind, placebo-controlled study in cancer patients scheduled to undergo tumor resection. Patients who provide consent are randomly allocated to receive oral administration of Yokukansan or placebo, and study drug administration is continued for 4 days or longer prior to surgery. We defined two primary endpoints, change in preoperative anxiety and incidence of postoperative delirium. Secondary endpoints are severity score of postoperative delirium, duration of postoperative delirium, amount of benzodiazepines used prior to surgery, amount of antipsychotic agents used after surgery, and number of postoperative hospitalization days. We plan to complete the analysis on March 31, 2021. The target number of registered patients is 110 per group, or 220 in total., Discussion: This study is the first randomized, double-blind, placebo-controlled study intended to clarify the effects of a Japanese herbal medicine, Yokukansan, in the prevention and treatment of perioperative psychiatric symptoms in patients with cancer. The trial was initiated on August 14, 2017, with 195 subjects randomized by October 5, 2018., Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000027561 . Registered on 31 May 2017.

Aim: This study was conducted to evaluate the performance of the ratio of urine and blood urea nitrogen concentration (UUN/BUN) as a new predictive factor for the response of an arginine vasopressin receptor 2 antagonist tolvaptan (TLV) in decompensated heart failure patients., Methods: This study enrolled 70 decompensated heart failure patients who were administered TLV at University of Tokyo Hospital. We collected the data of clinical parameters including UUN/BUN before administering TLV. Two different outcomes were defined as follows: having over 300 mL increase in urine volume on the first day (immediate urine output response) and having any decrease in body weight within one week after starting TLV treatment (subsequent clinical response)., Results: Among the 70 enrolled patients, 37 patients (52.9%) showed immediate urine output response; 51 patients (72.9%) showed a subsequent clinical response of body weight decrease. Receiver operating characteristics (ROC) analysis showed good prediction by UUN/BUN for the immediate response (AUC-ROC 0.86 [0.75-0.93]) and a significantly better prediction by UUN/BUN for the subsequent clinical response compared with urinary osmolality (AUC-ROC 0.78 [0.63-0.88] vs. 0.68 [0.52-0.80], P < 0.05)., Conclusions: We demonstrated that a clinical parameter of UUN/BUN can predict the response of TLV even when measured before TLV administration. UUN/BUN might enable identification of good responders for this new drug., (© 2015 Asian Pacific Society of Nephrology.)

Background: Observational studies have demonstrated similarities between the underpinning of frailty and biological features of centenarians, suggesting that adaptability to age-related multiple physiological decline may be a core component of successful aging. The aim of this study is to determine whether hormonal pathways potentially involved in energy homeostasis contribute to survival beyond 100 years of age., Methods: We assessed a total of 252 centenarians (mean [standard deviation (SD)] age, 101.5 (1.8) years, range 100-108 years) using a complete set of biomarkers of adipose endocrine function and the insulin-like growth factor-1 (IGF-1) axis. Conventional risk factors at baseline were also assessed. The participants were followed up for all-cause mortality every 12 months by telephone contact., Results: During 2253 days of follow-up, 208 centenarians (82.5%) died. The lowest tertile of leptin and the highest tertile of tumor necrosis factor-alpha were associated with higher mortality risk among centenarians after adjusting for age (per 6-month increase), sex, education, smoking, activities of daily living (ADL), cognitive function, and comorbidities (hazard ratio [HR] 1.6; 95% confidence interval [CI], 1.14-2.35; and HR 1.45; 95% CI, 1.00-2.08, respectively). The lowest tertiles of both IGF-1 and IGF binding protein 3 (IGFBP3) were also associated with increased mortality. The adipose risk score, indicating cumulative effects of adipokine dysregulation, was strongly associated with increased mortality risk; ADL; cognitive function; and levels of albumin, cholinesterase, high-density lipoprotein-cholesterol, C-reactive protein, interleukin 6, and IGF-1 at baseline., Conclusions: The results suggested that preservation of adipose endocrine function and the IGF-1 axis may be potentially important for maintaining health and function and promoting survival at an extremely old age.

Background: Research in Western countries has shown most centenarians to be survivors with multiple comorbidities. However, Japanese centenarians' morbidity and its relationship to functional status has yet to be elucidated. The aim of this study is to clarify the association of morbidity with the physical and cognitive function of centenarians. We examined Tokyo-area centenarians to determine their kinds of morbidity profiles and how such morbidity related to their functional status., Methods: We studied 302 centenarians living in Tokyo (101.2+/-1.8 years; 65 men, 237 women), and assessed their physical status, morbidity, and use of medication. Activities of daily living and cognitive function were also assessed using the Barthel Index and the Clinical Dementia Rating., Results: More than 95% of the centenarians had chronic diseases. Both the physical and cognitive functions were significantly higher in men. The present and previous illnesses most frequently included hypertension, heart disease, stroke, fractures, and cataracts. Fractures were observed significantly more frequently in women. Diabetes mellitus was uncommon. The physical and cognitive function of centenarians with a history of stroke or fracture were particularly poor, whereas those centenarians with hypertension tended to show a high level of physical and cognitive function., Conclusions: Almost all centenarians had chronic diseases. Stroke and fracture were correlated with poorer function; therefore, we hypothesize that prevention of stroke and fracture might improve functional status in the oldest-old.

Objective: To investigate age-associated changes in the circadian rhythm of the heart rate., Design: The circadian rhythm was extracted from diurnal heart rate (HR) variations, and patterns of HR rhythm were compared in centenarians and controls., Setting: Centenarians living in the metropolitan area of Tokyo and in Aichi prefecture in 1992., Participants: Fifty centenarians underwent 24-hour ambulatory electrocardiogram (Holter) monitoring. The control group, comprised of 100 clinically healthy subjects who underwent similar Holter monitoring, was subdivided, by age, into two groups: the younger controls (age range 23 to 54 years, mean age 41) and the older controls (age range 55 to 82 years, mean age 69)., Measurements: Harmonic analysis was used to approximate the 24-hour RR interval (the interval between two neighboring R waves on the electrocardiogram) data obtained by Holter monitoring to a summation of three cosine waves with 24-hour, 12-hour, and 8-hour periods. The power of the period was adjusted for the goodness of curve-fit. The power of each period and the circadian acrophase (the timing of the peak in a 24-hour rhythm) were compared among the centenarians, older controls, and younger controls. HR rhythms were classified by k-means cluster analysis based on the power of the period. The prevalence of each pattern was compared among the three age groups. In the centenarians, the relationship between clinical parameters (activities of daily living, cognitive function, nutritional status, and present illness) and patterns of HR rhythm was investigated., Results: The power of the 24-hour period in the centenarians was significantly smaller than that in the older (P < .05) and younger (P < .001) controls. The power of the 8-hour period in the centenarians was significantly larger than that in the younger controls (P < .05). Advances or delays in the circadian acrophase were frequently observed in the centenarians compared with the younger controls. The power of each period did not differ between centenarians with (n = 11) and without (n = 39) overt diseases capable of altering HR rhythms. Five patterns of HR rhythm were identified: 24-hour period dominant (n = 84), 24-hour+12-hour period (n = 18), 12-hour period dominant (n = 11), 8-hour period dominant (n = 7), and low goodness of curve-fit (n = 30). The 8-hour period dominant pattern and the low goodness of curve-fit pattern were observed commonly in the centenarians, whereas the 24-hour period dominant pattern and the 24-hour+12-hour period pattern were observed frequently in the younger controls. Patterns of HR rhythm were not related to clinical parameters in the centenarians., Conclusions: The circadian rhythm of HR changed with aging: there was reduction in the power of the 24-hour period, augmentation in the power of the 8-hour period, and a shift in the circadian acrophase.

To examine the relationship between apolipoprotein E (apoE) phenotype and life span, we measured the frequently of the apoE phenotype and allele in 54 Japanese centenarians who lived in the Tokyo metropolitan area in 1994, 1995, and 1996. The control group consisted of 973 subjects, 883 healthy volunteers who were described previously and 90 healthy people who came to the Keio health consulting center. The apoE phenotypes in the centenarians was 2 E2/E2 (3.7%), 5 E2/E3 (9.3%), 38 E3/E3 (70.4%), and 9 3E/E4 (16.7%). No other phenotype was observed. In the control group, the phenotypes were 2 E2/E2 (0.2%), 57 E2/E3 (5.9%) 712 E3/E3 (73.2%), and 179 E3/E4 (18.4%). The frequency of E2 was higher in the centenarians. The frequencies of the apoE allele in the centenarians and the control subjects were epsilon 2 8.3% vs. 3.5%, epsilon 3 83.3% vs. 85.4%, and epsilon 4 8.3% vs. 10.9%. The frequency of the apoE allele differed significantly between centenarians and control subjects (chi 2 = 6.84, p = 0.033). Levels of serum cholesterol and apolipoprotein B were significantly lower in the E2/E2 + E2/E3 centenarians. Studies of the frequency of the apoE allele in Japanese, French, and Finnish subjects showed that epsilon 2 is more frequent and epsilon 4 is less frequent in centenarians. These data show the apoE phenotype may affect life span: epsilon 2 is positively and epsilon 4 is negatively associated with longevity.

To establish the guideline for nutrition in the very old, we analyzed biochemical and hematological data from 45 Japanese centenarians living in Tokyo metropolitan area during 1994 and 1995. Levels of cholesterol, HDL-cholesterol, apolipoprotein A1 and B, albumin, prealbumin in serum were lower than in a control group or lower than the reference range, which indicates that these centenarians were undernourished. RBC counts, hemoglobin, and hematocrit were also low in the centenarians. The concentration of albumin correlated positively with those of HDL-cholesterol and apolipoprotein A1, and negatively with concentration of Lp(a). The value for transferrin correlated positively with energy intake and with the concentration of apolipoprotein A1. The concentration of prealbumin correlated positively with the concentration of hemoglobin, hematocrit and the total cholesterol concentration. According to their nutritional status, the centenarians were divided into 2 groups: well-nourished and undernourished. Those who were well-nourished had higher levels of cholesterol, HDL, Hb, and apolipoprotein A1, their levels of ADL and cognitive function were also high. The findings of blood-chemical data in the centenarians may be partly due to undernutrition. Centenarians who were well-nourished were considered to be aging successfully. These results and others previously published indicate that the concentrations of albumin, prealbumin, transferrin and either CRI or IL-6 are useful for nutritional assessment in the very old.