A Case of Thrombocytopenia, Anasarca (Edema, Pleural Effusion, and Ascites), Fever, Reticulin Fibrosis/Renal Dysfunction, and Organomegaly (TAFRO) Syndrome Initially Not Presenting With Thrombocytopenia: A Role of Immature Platelet Fraction.

Thrombocytopenia, anasarca (edema, pleural effusion, and ascites), fever, reticulin fibrosis/renal dysfunction, and organomegaly (TAFRO) syndrome is a rare and severe systemic disease. The emergence of thrombocytopenia, however, may be preceded by other signs or symptoms, which could delay the diagnosis of the disease. We reported a case in which an increased immature platelet fraction (IPF), a surrogate marker for megakaryocytic activity, preceded the development of thrombocytopenia, and finally, we diagnosed the patient with TAFRO syndrome. A 79-year-old male with a previous history of uninephrectomy due to bladder and ureteral cancer was admitted to our hospital because of massive edema and progressive impairment in renal function. On admission, inguinal lymphadenopathy, elevated C-reactive protein (CRP), bilateral pleural effusion, and ascites were observed, and the lymph node biopsy showed that atrophic lymphoid follicles and germinal centers were observed along with prominent glomeruloid vascular proliferation and the expansion of the interfollicular spaces consistent with the feature of Castleman's disease. The peripheral platelet count did not reach the level of the criteria for TAFRO syndrome (13.9×104/µL), but the immature platelet fraction was increased (11.6%), and bone marrow biopsy revealed hyperplasia of megakaryocytes. During the course of the preemptive treatment with prednisolone and tocilizumab, thrombocytopenia was uncovered, and the patient was finally diagnosed as having TAFRO syndrome. Thus, the present case may offer valuable information on the role of the immature platelet fraction in the establishment of the early diagnosis of TAFRO syndrome.

Superstructure of Fe5-xGeTe2 Determined by Te K-Edge Extended X-ray Absorption Fine Structure and Te Kα X-ray Fluorescence Holography.

The local structure of the two-dimensional van der Waals material, Fe5-xGeTe2, which exhibits unique structural/magnetic phase transitions, was investigated by Te K-edge extended X-ray absorption fine structure (EXAFS) and Te Kα X-ray fluorescence holography (XFH) over a wide temperature range. The formation of a trimer of Te atoms at low temperatures has been fully explored using these methods. An increase in the Te-Fe distance at approximately 150 K was suggested by EXAFS and presumably indicates the formation of a Te trimer. Moreover, XFH displayed clear atomic images of Te atoms. Additionally, the distance between the Te atoms shortened, as confirmed from the atomic images reconstructed from XFH, indicating the formation of a trimer of Te atoms, i.e., a charge-ordered superstructure. Furthermore, Te Kα XFH provided unambiguous atomic images of Fe atoms occupying the Fe1 site; the images were not clearly observed in the Ge Kα XFH that was previously reported because of the low occupancy of Fe and Ge atoms. In this study, EXAFS and XFH clearly showed the local structure around the Te atom; in particular, the formation of Te trimers caused by charge-ordered phase transitions was clearly confirmed. The charge-ordered phase transition is fully discussed based on the structural variation at low temperatures, as established from EXAFS and XFH.

Impact of dynamic parameter of trends in vital signs on the prediction of serious events in hospitalized patients -a retrospective observational study.

Aim: Although early detection of patients' deterioration may improve outcomes, most of the detection criteria use on-the-spot values of vital signs. We investigated whether adding trend values over time enhanced the ability to predict adverse events among hospitalized patients. Methods: Patients who experienced adverse events, such as unexpected cardiac arrest or unplanned ICU admission were enrolled in this retrospective study. The association between the events and the combination of vital signs was evaluated at the time of the worst vital signs 0-8 hours before events (near the event) and at 24-48 hours before events (baseline). Multivariable logistic analysis was performed, and the area under the receiver operating characteristic curve (AUC) was used to assess the prediction power for adverse events among various combinations of vital sign parameters. Results: Among 24,509 in-patients, 54 patients experienced adverse events(cases) and 3,116 control patients eligible for data analysis were included. At the timepoint near the event, systolic blood pressure (SBP) was lower, heart rate (HR) and respiratory rate (RR) were higher in the case group, and this tendency was also observed at baseline. The AUC for event occurrence with reference to SBP, HR, and RR was lower when evaluated at baseline than at the timepoint near the event (0.85 [95%CI: 0.79-0.92] vs. 0.93 [0.88-0.97]). When the trend in RR was added to the formula constructed of baseline values of SBP, HR, and RR, the AUC increased to 0.92 [0.87-0.97]. Conclusion: Trends in RR may enhance the accuracy of predicting adverse events in hospitalized patients.

Longitudinal relationship between screen-based sedentary behavior and nutrient intake in Japanese children: an observational epidemiological cohort study.

BACKGROUND: Concerns regarding the impact of screen-based sedentary behavior on health have been increasing. Therefore, the present study investigated the longitudinal relationship between multiple screen time and nutrient intake in children and adolescents. METHODS: The present study was conducted utilizing 3 years longitudinal data. Study subjects were 740 Japanese children aged between 6 and 12 years at baseline and between 9 and 15 years in the follow-up. Screen-based sedentary behavior was assessed using screen time, including television (TV) viewing, personal computer (PC) use, and mobile phone (MP) use. The main outcomes were the intakes of nutrients. Mixed effect multivariate linear regression analyses were used to examine the longitudinal relationship between screen-based sedentary time and nutrient intake. Covariates included in the multivariable analysis consisted of sex, age, solitary eating, skipping breakfast, staying up late, and body weight status, as confounders, and physical inactivity, as mediator. RESULTS: In boys, a longer total screen time longitudinally correlated with higher intake of energy and lower intakes of protein, dietary fiber, minerals, and vitamins. In girls, longer total screen time longitudinally associated with higher intake of sucrose and lower intakes of protein, minerals, and vitamins. In boys, a longer TV viewing time was associated with higher intake of sucrose and lower intakes of protein, minerals, and vitamins. In girls, a longer TV viewing time was associated with higher intake of carbohydrates and lower intakes of protein, fat, minerals, and vitamins. In boys, relationships were observed between a longer PC use time and higher intakes of energy as well as lower intakes of protein, minerals, and vitamins. Relationship was observed between longer PC use time and lower intakes of minerals in girls. An increased MP use time was associated with higher intakes of energy, and lower intakes of protein, sucrose, dietary fiber, minerals, and vitamins in boys. A longer MP use time was associated with higher intakes of fat, and salt as well as lower intakes of carbohydrates, protein, minerals, and vitamins in girls. CONCLUSIONS: The present results revealed that longer screen-based sedentary behaviors were longitudinally associated with nutrient intake in children and adolescents. Future study is needed to elucidate these relationships.

Pressure Dependence of the Structural and Superconducting Properties of the Bi-Based Superconductor Bi2Pd3Se2.

The structural and superconducting properties of the Bi-based compound Bi2Pd3Se2 were investigated over a wide pressure range. The prepared Bi2Pd3Se2 sample was a superconductor with a superconducting transition temperature, Tc, of approximately 3.0 K, which differed from a previous report (Tc of less than 1.0 K). At ambient pressure, the powder X-ray diffraction (XRD) pattern of the Bi2Pd3Se2 sample was consistent with that previously reported for Bi2Pd3Se2. The Rietveld method was used to refine the crystal structure, which had a space group of C2/m (No. 12), as reported previously. This compound showed no clear anomaly due to the charge-density-wave (CDW) transition, as seen from the temperature dependence of magnetic susceptibility. However, the temperature dependence of electrical resistivity indicated a clear anomaly, presumably because of the CDW transition in the low-pressure range; the CDW transition temperature was approximately 230 K. The XRD patterns of the Bi2Pd3Se2 sample were measured at 0.160-22.7 GPa, and the patterns were well analyzed by both the Le Bail and Rietveld refinement methods, showing no structural phase transitions in the above pressure range. The pressure dependence of Tc of Bi2Pd3Se2 was recorded based on the temperature dependence of the electrical resistance, which showed an almost constant Tc at 0-13.7 GPa, and the Tc-pressure (p) behavior was fully discussed.

Observation of the Superstructure in Fe5-xGeTe2 by X-ray Fluorescence Holography.

Fe5-xGeTe2 is a two-dimensional van der Waals material that exhibits ferromagnetic order with a high Curie temperature (TC) of around room temperature. In addition to TC, two magnetic transitions occur with decreasing temperature, and a charge-ordered state is observed at low temperatures. We employed Ge Kα X-ray fluorescence holography (XFH) for Fe5-xGeTe2 to directly investigate the local structure in the charge-ordered state, i.e., the 3×3 superstructure. The Ge Kα XFH results revealed local atomic structures around the Ge atom, thus clarifying the simultaneous locations and arrangements of the Te, Fe, and Ge atoms. The atomic positions relative to the Ge atom are useful for understanding the coexistence of the ideal 1 × 1 structure and 3×3 superstructure found in the charge-ordered state.

Functional Recovery and Nutrition Management among Severe COVID-19 Cases during Post-extubation Hospitalization: A Case Series.

Background: Many patients with coronavirus disease 2019 (COVID-19) develop malnutrition after a prolonged stay in the intensive care unit (ICU) with mechanical ventilation. Early enteral nutrition is recommended, but optimal nutrition management during post-extubation recovery remains challenging. Cases: The subjects were 12 acute respiratory distress syndrome patients with COVID-19 (9 men, 3 women; median age, 55.6 years). We reviewed patient characteristics, physical function, and nutrient intake during hospitalization from just after extubation to discharge. During this period, the median Functional Oral Intake Scale score improved from 4.5 (interquartile range [IQR] 3.3-5.3) to 7.0 (IQR 5.8-7.0), the median Medical Research Council (MRC) scale score improved from 45.0 (IQR 39.3-48.5) to 53.5 (IQR 47.5-59.3), and the median Barthel index improved from 7.5 (IQR 0-16.3) to 72.5 (IQR 42.5-95.0). In 3 patients, the MRC scale score remained below 48 before discharge, indicating that ICU-acquired weakness had been prolonged. The median daily caloric intake during this phase increased from 6.9 kcal/kg per day (3.5-10.2 kcal/kg per day) to 24.8 kcal/kg per day (21.0-27.9 kcal/kg per day). About half of these patients showed caloric intake below 25 kcal/kg per day before discharge. Based on the Global Leadership Initiative on Malnutrition (GLIM) diagnostic scheme, 10 patients were diagnosed with malnutrition during hospitalization. Discussion: Physical function improved in more than half of the patients, but nutritional status was not recovered. More studies for nutritional management are required to prevent malnutrition and to enhance functional recovery during the post-extubation rehabilitation phase.

Direct Observation of Group-V Dopant Substitutional Defects in CdTe Single Crystals.

Point defect chemistry strongly affects the fundamental properties of materials and has a decisive impact on device performance. The Group-V dopant is prominent acceptor species with high hole concentration in CdTe; however, its local atomic structure is still not clear owing to difficulties in definitive measurements and discrepancies between experimental observations and theoretical models. Herein, we report on direct observation of the local structure for the As dopant in CdTe single crystals by the X-ray fluorescence holography (XFH) technique, which is a powerful tool to visualize three-dimensional atomic configurations around a specific element. The XFH result shows the As substituting on both Cd (AsCd) and Te (AsTe) sites. Although AsTe has been well known as a shallow acceptor, AsCd has not attracted much attention and been discussed so far. Our results provide new insights into point defects by expanding the experimental XFH study in combination with theoretical first-principles studies in II-VI semiconductors.

Sustained effect of leukocytapheresis/granulocytapheresis versus anti-human TNF-α monoclonal antibody on ulcerative colitis: A 2-year retrospective study.

Although anti-tumor necrosis factor-α monoclonal antibody biological preparations (BP) agents are widely used as an established treatment tool for refractory ulcerative colitis (UC), whether leukocytapheresis/granulocytapheresis (L/G-CAP) has similar beneficial impact on the disease activity remains undetermined. Furthermore, the costs defrayed for the treatment with these 2 modalities have not been compared. We retrospectively evaluated whether L/G-CAP offered sustained beneficial effects over 2-year period. The patients who had moderately to severely active UC (Rachmilewitz clinical activity index (CAI) ≧ 5) and were treated with a series (10 sessions) of L/G-CAP (n = 19) or BP (n = 7) as an add-on therapy to conventional medications were followed. Furthermore, the cost-effectiveness pertaining to the treatment with L/G-CAP and BP was assessed over 12 months. At baseline, L/G-CAP and BP groups manifested similar disease activity (CAI, L/G-CAP; 7.0 [6.0-10.0], BP; 10.0 [6.0-10.0], P = .207). The L/G-CAP and BP treatment suppressed the activity, with CAI 1 or less attained on day 180. When the L/G-CAP group was dichotomized into L/G-CAP-high and L/G-CAP-low group based on CAI values (≥3 or < 3) on day 365, CAI was gradually elevated in L/G-CAP-high group but remained suppressed in L/G-CAP-low group without additional apheresis for 2 years. Anemia was corrected more rapidly and hemoglobin levels were higher in BP group. The cost of the treatment with L/G-CAP over 12 months was curtailed to 76% of that with BP (1.79 [1.73-1.92] vs 2.35 [2.29-3.19] million yen, P = .028). L/G-CAP is as effective as BP in a substantial number of patients over 2 years. The cost for the treatment of UC favors L/G-CAP although the correction of anemia may prefer BP. Thus, L/G-CAP can effectively manage the disease activity with no additional implementation for 2 years although further therapeutic modalities might be required in a certain population with high CAI observed on day 365.

Effects of Oxygen on Lattice Defects in Single-Crystalline Mg2Si Thermoelectrics.

Lattice defect engineering has attracted attention due to its ability to develop thermoelectric materials with low thermal conductivity. For Mg2Si single crystals (SCs), Si vacancy (VSi) defects can be introduced and consequently result in the formation of dislocation cores. These lattice defects confer Mg2Si SCs with a lower thermal conductivity compared to Mg2Si polycrystals. To reveal a mechanism for the stabilisation of VSi in the Mg2Si SCs, we investigated the effects of oxygen (O) on lattice defects by performing electronic structure calculations, secondary ion mass spectrometry, X-ray photoelectron spectroscopy, and photoelectron holography. On the basis of these calculations, we predicted that O stabilised the formation of VSi when it was located at the Si site or at an interstitial site. All experiments confirmed the presence of O inside the Mg2Si SCs. However, O was suggested to be located not at the specific site in the crystal lattice of Mg2Si but at dislocation cores. The interaction between O and the dislocation cores in the Mg2Si SC is expected to immobilise dislocation cores, leading to the stabilisation of VSi formation.

Impact of early initiation of renin-angiotensin blockade on renal function and clinical outcomes in patients with hypertensive emergency: a retrospective cohort study.

BACKGROUND: Hypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the renin-angiotensin-aldosterone (RAA) system is enormously activated in this disease, there are few reports that attempt to characterize the effect of early use of RAA inhibitors (RASi) on the temporal course of kidney function. METHODS: This retrospective cohort study was conducted to clarify whether the early use of RASi during hospitalization offered more favorable benefits on short-term renal function and long-term renal outcomes in patients with hypertensive emergencies. We enrolled a total of 49 patients who visited our medical center with acute severe hypertension and multiple organ dysfunction between April 2012 and August 2020. Upon admission, the patients were treated with intravenous followed by oral antihypertensive drugs, including RASi and Ca channel blockers (CCB). Kidney function as well as other laboratory and clinical parameters were compared between RASi-treated and CCB- treated group over 2 years. RESULTS: Antihypertensive treatment effectively reduced blood pressure from 222 ± 28/142 ± 21 to 141 ± 18/87 ± 14 mmHg at 2 weeks and eGFR was gradually restored from 33.2 ± 23.3 to 40.4 ± 22.5 mL/min/1.73m2 at 1 year. The renal effect of antihypertensive drugs was particularly conspicuous when RASi was started in combination with other conventional antihypertensive drugs at the early period of hospitalization (2nd day [IQR: 1-5.5]) and even in patients with moderately to severely diminished eGFR (< 30 mL/min/1.73 m2) on admission. In contrast, CCB modestly restored eGFR during the observation period. Furthermore, renal survival probabilities were progressively deteriorated in patients who had manifested reduced eGFR (< 15 mL/min/1.73 m2) or massive proteinuria (urine protein/creatinine ≥ 3.5 g/gCr) on admission. Early use of RASi was associated with a favorable 2-year renal survival probability (0.90 [95%CI: 0.77-1.0] vs. 0.63 [95%CI: 0.34-0.92] for RASi ( +) and RASi (-), respectively, p = 0.036) whereas no apparent difference in renal survival was noted for CCB. CONCLUSIONS: Early use of RASi contributes to the renal functional recovery from acute reduction in eGFR among patients with hypertensive emergencies. Furthermore, RASi offers more favorable effect on 2-year renal survival, compared with CCB.

Higher Intake of Vegetable Protein and Lower Intake of Animal Fats Reduce the Incidence of Diabetes in Non-Drinking Males: A Prospective Epidemiological Analysis of the Shika Study.

Although nutrient intake and alcohol consumption are both closely associated with the incidence of diabetes, their interrelationships remain unclear. Therefore, we herein have investigated the interrelationships among nutrient intake, alcohol consumption, and the incidence of diabetes using longitudinal data. This study included 969 residents ≥40 years living in Japan. In 2011 and 2012, a baseline study was conducted using questionnaires on basic demographics, diabetes, nutrient intake, and lifestyle habits. In 2018 and 2019, a follow-up study was performed using questionnaires and medical records on diabetes. Two-way analysis of covariance (two-way ANCOVA) was used to test the interactions of drinking habits and diabetes incidence on nutrients intake. The prospective relationship between nutrient intake at baseline and the incidence of diabetes in the follow-up stratified by drinkers and non-drinkers was evaluated using multiple logistic regression analysis. Interactions were observed for vegetable protein intake (p = 0.023) and animal fat intake (p = 0.016) in males. Vegetable protein intake negatively correlated with the incidence of diabetes in non-drinkers (odds ratio (OR): 0.208; 95% confidence interval (95% CI): 0.046-0.935; p = 0.041). Furthermore, animal fat intake positively correlated with the incidence of diabetes in non-drinkers (OR: 1.625; 95% CI: 1.020-2.589; p = 0.041). Therefore, vegetable protein and animal fat intakes in combination with drinking habits need to be considered for the prevention of diabetes.

Association between regional cerebral oxygen saturation and outcome of patients with out-of-hospital cardiac arrest: An observational study.

Aim: This study aimed to evaluate the association between cerebral oxygen saturation (StO2) and return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA). Methods: We retrospectively evaluated the data of patients with OHCA to determine the association between ROSC and various StO2 parameters (initial_StO2, final_StO2, mean_StO2, and Δ_StO2 [=final_StO2-initial_StO2]). Time-domain near-infrared spectroscopy was used to determine absolute StO2 values. Results: Of the 108 patients with OHCA, 23 achieved ROSC. Although initial_StO2 values did not differ between the groups, final_StO2, mean_StO2, and Δ_StO2 were higher in the ROSC group than in the non-ROSC group. The cut-off values for initial_StO2, mean_StO2, and Δ_StO2 as predictors of ROSC were 35%, 30%, and 5%, respectively. The odds ratio for ROSC had markedly increased in the Δ_StO2 ≥ 5% subgroup (19.70 [6.06-64.11], p < 0.001). When the change in StO2 (=d_StO2) at 8 min from the initiation of StO2 measurement was assessed, the d_StO2 ≥ 5% subgroup had a higher odds ratio for ROSC than the d_StO2 < 5% subgroup (5.8 [1.78-18.85], p = 0.002), and this tendency was maintained until 20 min. In the evaluation using a two-by-two contingency table with initial_StO2 and Δ_StO2 as two parameters, 61.9% of the patients fell under the categories of initial_StO2 < 35% and Δ_StO2 < 5% and had the lowest rate of ROSC achievement (4.6%). In the Δ_StO2 ≥ 5% subgroup, approximately-two-thirds of the patients achieved ROSC irrespective of the initial_StO2 (initial_StO2 ≥ 35%, 66.7%; initial_StO2 < 35%, 60.0%). Conclusions: Initial_StO2 and Δ_StO2 were associated with the achievement of ROSC.

Prospective relationship between autistic traits and nutrient intakes among Japanese children: Results of the Shika study.

LAY ABSTRACT: It is known about food selectivity among children with autism spectrum disorder. However, the nutritional inadequacy among children with ASD is not clear. Especially, long-term evaluation has not been studied. We examined the prospective relationship between autistic traits in children and subsequent nutrient intake in later childhood. We utilized data obtained at two time points from a study conducted in Japan. Participants were 759 Japanese children aged between 7 and 12 years at baseline and between 10 and 15 years in the follow-up. The results showed relatively lower intakes of sodium, calcium, magnesium, iron, vitamin D, vitamin B2, and vitamin B12 among children with than without autistic traits. Relatively lower intake of minerals and vitamins in children with autistic traits is more evident in later childhood. The results suggest the importance of screening the nutrient intake of children with autistic traits across childhood.

Relationship between Vitamin Intake and Resilience Based on Sex in Middle-Aged and Older Japanese Adults: Results of the Shika Study.

Epidemiological studies reported that resilience, generally regarded as the ability to manage stress in the face of adversity, correlates with mental health in middle-aged and older adults. Currently, there is limited information on eating habits that affect resilience. Therefore, this cross-sectional study investigated the relationship between vitamin intake and resilience based on sex in community-dwelling middle-aged and older individuals in Shika town, Ishikawa Prefecture, Japan. A total of 221 participants (106 men and 115 women) aged 40 years or older were included in the analysis. We assessed vitamin intake and resilience using a brief-type self-administered diet history questionnaire (BDHQ) and the resilience scale (RS), respectively. A two-way analysis of covariance (ANCOVA) revealed that higher intakes of ß-carotene and vitamin K were associated with higher RS in women, but not in men. Furthermore, a multiple logistic regression analysis stratified by sex showed that ß-carotene and vitamin K were significant independent variables for RS only in women. The present study suggests that higher intakes of ß-carotene and vitamin K were associated with higher resilience among middle-aged and older women. The results obtained demonstrate that ß-carotene and vitamin K intakes may enhance resilience by strengthening stress tolerance.

Efficacy and safety of self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (MND-2119) versus highly purified eicosapentaenoic acid ethyl ester in patients with hypertriglyceridemia: Results from a 12-week randomized, double-blind, active-controlled, phase 3 study.

BACKGROUND: In Japan, eicosapentaenoic acid ethyl ester (EPA-E) is administered twice-daily or three-times-daily for dyslipidemia. We have developed MND-2119, a novel self-emulsifying formulation of highly purified EPA-E, which can be administered once-daily. OBJECTIVE: The objective of this study was to assess non-inferiority in the efficacy of MND-2119 in patients with hypertriglyceridemia compared with highly purified EPA-E. METHODS: In this multicenter, 12-week, double-blind study, patients with high triglyceride (TG levels between ≥ 150 and < 500 mg/dL) undergoing lifestyle modification were randomized to MND-2119 2 g/day (n=145), MND-2119 4 g/day (n=145), EPA-E 1.8 g/day (n=145) or EPA-E 2.7 g/day (n=145). The primary endpoint was percentage change in TG levels from baseline to end of treatment. RESULTS: MND-2119 2, 4 g/day and EPA-E 1.8, 2.7 g/day reduced TG levels from baseline by -10.09%, -15.51%, -9.30%, and -8.80%, respectively. The TG reduction rate of MND-2119 2 g/day was non-inferior to that of EPA-E 1.8 g/day (LS mean difference: -0.42, 95%CI: -5.76 to 4.91). Moreover, the TG reduction rate of MND-2119 4 g/day was superior to that of MND-2119 2 g/day (LS mean difference: -5.74, 95%CI: -10.59 to -0.89). There were no remarkable safety differences between MND-2119 2 g/day and EPA-E 1.8 g/day and between MND-2119 4 g/day and EPA-E 2.7 g/day. CONCLUSION: Non-inferiority of MND-2119 2 g/day to EPA-E 1.8 g/day for efficacy, and superiority of MND-2119 4 g/day over MND-2119 2 g/day for efficacy were verified. MND-2119 was safe and well tolerated.

Eleven-year retrospective study characterizing patients with severe brain damage and poor neurological prognosis -role of physicians' attitude toward life-sustaining treatment.

BACKGROUND: Severe brain hemorrhage/infarction and cardiac arrest constitute the most critical situations leading to poor neurological prognosis. Characterization of these patients is required to offer successful end-of-life care, but actual practice is affected by multiple confounding factors, including ethicolegal issues, particular in Japan and Asia. The aim of this study is to evaluate the clinical courses of patients with severe brain damage and to assess the preference of end-of-life care for these patients in Japanese hospitals. METHODS: A retrospective observational study was conducted between 2008 and 2018. All intracranial hemorrhage/infarction and cardiac arrest out-patients (n = 510) who were admitted to our two affiliated hospitals and survived but with poor neurologic outcomes were included. Demographic characteristics as well as prognosis and treatment policies were also assessed. RESULTS: Patients were divided into two categories; cases with absent brainstem reflex (BSR) (BSR[-]) and those with preserved BSR (BSR[ +]). The survival rate was higher and the length of hospitalization was longer in patients with BSR[ +] than in those with BSR[-]. Among three life-sustaining policies (i.e., aggressive treatment, withdrawal of treatment, and withholding of treatment), withholding of treatment was adopted to most patients. In BSR[-], the proportion of three treatment policies performed at the final decision did not differ from that at the initial diagnosis on neurological status (p = 0.432). In contrast, this proportion tended to be altered in BSR[ +] (p = 0.072), with a decreasing tendency of aggressive treatment and a modest increasing tendency of withdrawal of treatment. Furthermore, the requests from patients' families to withdraw life-sustaining treatment, including discontinuation of mechanical ventilation, increased, but actual implementation of withdrawal by physicians was less than half of the requests. CONCLUSIONS: BSR constitutes a crucial determinant of mortality and length of hospitalization in comatose patients with severe brain damage. Although the number of withdrawal of life-sustaining treatment tends to increase over time in BSR[ +] patients, there are many more requests from patients' families for withdrawal. Since physicians has a tendency to desist from withdrawing life-sustaining treatment, more in-depth communication between medical staff and patients' families will facilitate mutual understanding over ethicolegal and religious issues and may thus improve end-of-life care.

Ultrafiltration in Japanese critically ill patients with acute kidney injury on renal replacement therapy.

A recent worldwide survey indicates an international diversity in net ultrafiltration (UFNET) practices for the treatment of fluid overload in critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT). The sub-analysis of the survey has demonstrated that maximum doses of furosemide used before determination of diuretic resistance are lower in Japan than those prescribed worldwide and UFNET is lower but is initiated earlier. In contrast, the interval during which practitioners evaluate fluid balance is longer. The characterization of RRT in critically ill patients in Japan should unveil more appropriate approaches to the successful treatment of AKI.

Role of a rapid response system and code status discussion as determinants of prognosis for critical inpatients: An observational study in a Japanese urban hospital.

ABSTRACT: Rapid response systems (RRS) have been introduced worldwide to reduce unpredicted in-hospital cardiac arrest (IHCA) and in-hospital mortality. The role of advance care planning (ACP) in the management of critical patients has not yet been fully determined in Japan.We retrospectively assessed the characteristics of all inpatients with unpredicted IHCA in our hospital between 2016 and 2018. Yearly changes in the number of RRS activations and the incidence of unpredicted IHCA with or without code status discussion were evaluated from 2014 to 2018. Hospital standardized mortality ratios were assessed from the data reported in the annual reports by the National Hospital Organization.A total of 81 patients (age: 70.9 ±â€Š13.3 years) suffered an unpredicted IHCA and had multiple background diseases, including heart disease (75.3%), chronic kidney disease (25.9%), and postoperative status (cardiovascular surgery, 18.5%). Most of the patients manifested non-shockable rhythms (69.1%); survival to hospital discharge rate was markedly lower than that with shockable rhythms (26.8% vs 72.0%, P < .001). The hospital standardized mortality ratios was maintained nearly constant at approximately 50.0% for 3 consecutive years. The number of cases of RRS activation markedly increased from 75 in 2014 to 274 patients in 2018; conversely, the number of unpredicted IHCA cases was reduced from 40 in 2014 to 18 in 2018 (P < .001). Considering the data obtained in 2014 and 2015 as references, the RRS led to a reduction in the relative risk of unpredicted IHCA from 2016 to 2018 (ie, 0.618, 95% confidence interval 0.453-0.843). The reduction in unpredicted IHCA was attributed partly to the increased number of patients who had discussed the code status, and a significant correlation was observed between these parameters (R2 = 0.992, P < .001). The reduction in the number of patients with end-stage disease, including congestive heart failure and chronic renal failure, paralleled the incidence of unpredicted IHCA.Both RRS and ACP reduced the incidence of unpredicted IHCA; RRS prevents progression to unpredicted IHCA, whereas ACP decreases the number of patients with no code status discussion and thus potentially reducing the patient subgroup progressing to an unpredicted IHCA.

Effects of SGLT2 inhibitors on eGFR in type 2 diabetic patients-the role of antidiabetic and antihypertensive medications.

Recent randomized trials demonstrating the beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in type 2 diabetes suggest that early reductions in eGFR upon initiation of SGLT2i therapy are associated with improved renal outcomes. Multiple concomitant medications, including antidiabetic and antihypertensive agents, are commonly used, however, which may modify the renal hemodynamic action of SGLT2is. Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (-2.29 ± 0.90 vs -5.85 ± 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively). Other antidiabetic agents (DPP4 inhibitors, sulfonylureas and insulin) had no effect on the eGFR response to SGLT2is. Antihypertensive drugs, including calcium channel blockers (CCBs) and ß blockers, did not affect the SGLT2i-induced changes in eGFR, whereas renin-angiotensin system inhibitors (RASis) tended to enhance this response (p = 0.059). Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is. Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 ± 1.28 vs. 4.60 ± 1.15 mL/min/1.73 m2 in eGFR, p = 0.028). No interaction between metformin and insulin or between metformin and DPP4 inhibitors was observed. In conclusion, metformin blunts the SGLT2i-induced decrease in eGFR, but coadministration of RASis ameliorates this response. Furthermore, the inability of CCBs to modify the SGLT2i-induced reduction in eGFR suggests that the SGLT2i-induced renal microvascular action is mediated predominantly by postglomerular vasodilation rather than preglomerular vasoconstriction.