Kota Ono

Recombinant human soluble thrombomodulin and mortality in sepsis-induced disseminated intravascular coagulation : a multicentre retrospective study

Recombinant human soluble thrombomodulin (rhTM) is a novel class of anticoagulants for treating disseminated intravascular coagulation (DIC). Although rhTM is widely used in clinical settings throughout Japan, there is limited clinical evidence supporting the use of rhTM in patients with sepsis-induced DIC. Furthermore, rhTM is not approved for DIC treatment in other countries. This study aimed to clarify the survival benefits of rhTM administration in critically ill patients. Data from 3,195 consecutive adult patients who were admitted to 42 intensive care units for the treatment of severe sepsis or septic shock between January 2011 and December 2013 were retrospectively analysed, and 1,784 patients were diagnosed with DIC based on the scoring algorithm from the Japanese Association for Acute Medicine DIC (n = 645, rhTM group; n = 1,139, control group). Propensity score matching created 452 matched pairs, and logistic regression analysis revealed a significant association between rhTM administration and lower in-hospital all-cause mortality in the propensity score-matched groups (odds ratio, 0.757; 95 % confidence interval, 0.574-0.999, p = 0.049). Inverse probability of treatment weighted and quintile-stratified analyses also revealed significant associations between rhTM administration and lower in-hospital all-cause mortality. Survival time in the propensity score-matched rhTM group was significantly longer than that in the propensity score-matched control group (hazard ratio, 0.781; 95 % confidence interval, 0.624-0.977, p = 0.03). Bleeding complications were not more frequent in the rhTM groups. In conclusion, this study demonstrated that rhTM administration is associated with reduced in-hospital all-cause mortality among patients with sepsis-induced DIC.

Antithrombin Supplementation and Mortality in Sepsis-induced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study

ABSTRACT Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572–0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646–1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649–1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

Comparative effects of vildagliptin and sitagliptin determined by continuous glucose monitoring in patients with type 2 diabetes mellitus

The dipeptidyl peptidase-4 inhibitors vildagliptin and sitagliptin are effective in treating patients with type 2 diabetes mellitus. Patients receiving standard doses of sitagliptin plus insulin may require increased doses of sitagliptin or switching to vildagliptin to improve blood glucose control. This study compared the effects of increasing sitagliptin and switching to vildagliptin in type 2 diabetes patients receiving standard doses of sitagliptin plus insulin. This prospective, randomized, parallel-group comparison trial enrolled 33 type 2 diabetes patients receiving 50 mg sitagliptin once daily plus insulin. Seventeen patients were randomized to 50 mg vildagliptin twice daily, and 16 to 100 mg sitagliptin once daily, and evaluated by continuous glucose monitoring at baseline and after 8 weeks. The primary end-point was the change in mean amplitude of glycemic excursions (MAGE). MAGE decreased from baseline in both the vildagliptin (-13.4 ± 35.7 mg/dL) and sitagliptin (-8.4 ± 24.3 mg/dL) groups, but neither within- nor between-group changes were statistically significant. Similarly, the areas under the curve for blood glucose levels ≥180 mg/dL and <70 mg/dL tended to improve in both groups, but these differences were not statistically significant. In contrast, HbA1c was significantly reduced only in the vildagliptin group, from 7.1 ± 0.6% at baseline to 6.8 ± 0.6% at 8 weeks (p=0.006). Increasing sitagliptin dose and switching to vildagliptin had limited effects in improving MAGE in type 2 diabetic patients treated with standard doses of sitagliptin.

Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in Japan

We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed‐up for >6 months or had died within 6 months. Seventy‐two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow‐up was 52.6 (range, 6.3–131.9) months. The 5‐year overall survival, progression‐free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression‐free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [n = 3 patients; 3.1%]). No treatment‐related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow‐up are warranted.

The Survival Benefit of a Novel Trauma Workflow that Includes Immediate Whole-body Computed Tomography, Surgery, and Interventional Radiology, All in One Trauma Resuscitation Room: A Retrospective Historical Control Study.

Objective: The aim of this study was to evaluate the impact of a novel trauma workflow, using an interventional radiology (IVR)–computed tomography (CT) system in severe trauma. Background: In August 2011, we installed an IVR-CT system in our trauma resuscitation room. We named it the Hybrid emergency room (ER), as it enabled us to perform all examinations and treatments required for trauma in a single place. Methods: This retrospective historical control study conducted in Japan included consecutive severe (injury severity score ≥16) blunt trauma patients. Patients were divided into 2 groups: Conventional (from August 2007 to July 2011) or Hybrid ER (from August 2011 to July 2015). We set the primary endpoint as 28-day mortality. The secondary endpoints included cause of death and time course from arrival to start of CT and surgery. Multivariable logistic regression analysis adjusted for clinically important variables was performed to evaluate the clinical outcomes. Results: We included 696 patients: 360 in the Conventional group and 336 in the Hybrid ER group. The Hybrid ER group was significantly associated with decreased mortality [adjusted odds ratio (OR), 0.50 (95% confidence interval, 95% CI, 0.29–0.85); P = 0.011] and reduced deaths from exsanguination [0.17 (0.06–0.47); P = 0.001]. The time to CT initiation [Conventional 26 (21 to 32) minutes vs Hybrid ER 11 (8 to 16) minutes; P < 0.0001] and emergency procedure [68 (51 to 85) minutes vs 47 (37 to 57) minutes; P < 0.0001] were both shorter in the Hybrid ER group. Conclusion: This novel trauma workflow, comprising immediate CT diagnosis and rapid bleeding control without patient transfer, as realized in the Hybrid ER, may improve mortality in severe trauma.

Adaptive Servo-Ventilation Has More Favorable Acute Effects on Hemodynamics Than Continuous Positive Airway Pressure in Patients With Heart Failure

Adaptive servo-ventilation (ASV) has been attracting attention as a novel respiratory support therapy for heart failure (HF). However, the acute hemodynamic effects have not been compared between ASV and continuous positive airway pressure (CPAP) in HF patients.We studied 12 consecutive patients with stable chronic HF. Hemodynamic measurement was performed by right heart catheterization before and after CPAP 5 cmH2O, CPAP 10 cmH2O, and ASV for 15 minutes each.Heart rate, blood pressure, pulmonary capillary wedge pressure (PCWP), and stroke volume index (SVI) were not changed by any intervention. Right atrial pressure significantly increased after CPAP 10 cmH2O (3.6 ± 3.3 to 6.7 ± 1.6 mmHg, P = 0.005) and ASV (4.1 ± 2.6 to 6.8 ± 1.5 mmHg, P = 0.026). Cardiac index was significantly decreased by CPAP 10 cmH2O (2.3 ± 0.4 to 1.9 ± 0.3 L/minute/m(2), P = 0.048), but was not changed by ASV (2.3 ± 0.4 to 2.0 ± 0.3 L/ minute/m(2), P = 0.299). There was a significant positive correlation between baseline PCWP and % of baseline SVI by CPAP 10 cmH2O (r = 0.705, P < 0.001) and ASV (r = 0.750, P < 0.001). ASV and CPAP 10 cmH2O had significantly greater slopes of this correlation than CPAP 5 cmH2O, suggesting that patients with higher PCWP had a greater increase in SVI by ASV and CPAP 10 cmH2O. The relationship between baseline PCWP and % of baseline SVI by ASV was shifted upwards compared to CPAP 10 cmH2O. Furthermore, based on the results of a questionnaire, patients accepted CPAP 5 cmH2O and ASV more favorably compared to CPAP 10 cmH2O.ASV had more beneficial effects on acute hemodynamics and acceptance than CPAP in HF patients.

Surveillance for the use of mycophenolate mofetil for adult patients with lupus nephritis in Japan

Objectives. Mycophenolate mofetil (MMF) is used as one of the standard induction/maintenance protocols for lupus nephritis (LN). However, MMF has not been approved for treating LN in any country, resulting in worldwide off-label use of this immunosuppressant. In order to clarify the real-world use of MMF as a treatment for LN in Japan, Japan College of Rheumatology surveyed the use of MMF in daily clinical practice. Methods. Adult patients with LN who visited enrolled hospitals from October 2008 to September 2013 were surveyed for the initial, maximum, and maintenance doses of MMF. The safety and efficacy of MMF were retrospectively evaluated. Results. One hundred and thirty-seven LN patients including 116 females were enrolled. The median of initial, maximum, and maintenance doses of MMF were 1.0 g/day, 1.5 g/day, and 1.0 g/day, respectively. Sixty-one adverse events were reported in 39 patients during the follow-up period. Median urine protein level decreased from 1.89 g/gCr to 0.21 g/gCr, meanC3 level increased from 66.4 mg/dl to 80.3 mg/dl, and median anti-DNA antibody titer decreased from 40.6 IU/ml to 10.6 IU/ml. Conclusion. MMF was commonly used for the treatment of adult LN patients with acceptable efficacy and safety in Japan.

Morphofunctional cardiac changes in pregnant women: associations with biomarkers

Objective This longitudinal study was performed to determine changes in echocardiography parameters in association with various biomarker levels in pregnancy/postpartum. Methods Fifty-one healthy pregnant women underwent echocardiography with simultaneous determination of blood levels of five biomarkers at each of the first, second and third trimesters of pregnancy, immediately postpartum within 1 week after childbirth and approximately 1 month postpartum. Data on 255 echocardiography scans (five times per woman) and biomarkers were analysed. Results Left ventricular end-diastolic dimension, left atrial (LA) volume index and left ventricular (LV) mass index increased with advancing gestation and reached the maximum immediately postpartum concomitant with the highest brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI) and creatine kinase MB levels. The inferior vena cava diameter was significantly reduced in the third trimester compared with that in the first trimester and the peak occurred immediately after childbirth. In 255 paired measurements, hs-TnI level was significantly positively correlated with LA volume index and LV mass index; BNP and NT-proBNP were significantly positively correlated with LA volume index and estimated glomerular filtration rate (eGFR) was significantly positively correlated with the average of early diastolic septal and lateral mitral annular velocity (e′). Conclusions Maximal cardiac changes in morphology occurred postpartum within 1 week after childbirth, not during pregnancy. BNP/NT-proBNP, hs-TnI and eGFR reflected cardiac changes in pregnancy.

Optimal Antithrombin Activity Threshold for Initiating Antithrombin Supplementation in Patients With Sepsis-Induced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study:

Low-dose antithrombin supplementation therapy (1500 IU/d for 3 days) improves outcomes in patients with sepsis-induced disseminated intravascular coagulation (DIC). This retrospective study evaluated the optimal antithrombin activity threshold to initiate supplementation, and the effects of supplementation therapy in 1033 patients with sepsis-induced DIC whose antithrombin activity levels were measured upon admission to 42 intensive care units across Japan. Of the 509 patients who had received antithrombin supplementation therapy, in-hospital mortality was significantly reduced only in patients with very low antithrombin activity (≤43%; bottom quartile; adjusted hazard ratio: 0.603; 95% confidence interval: 0.368-0.988; P = .045). Similar associations were not observed in patients with low, moderate, or normal antithrombin activity levels. Supplementation therapy did not correlate with the incidence of bleeding requiring transfusion. The adjusted hazard ratios for in-hospital mortality increased gradually with antithrombin activity only when initial activity levels were very low to normal but plateaued thereafter. We conclude that antithrombin supplementation therapy in patients with sepsis-induced DIC and very low antithrombin activity may improve survival without increasing the risk of bleeding.

A Prospective Observational Study on Effect of Short‐Term Periodic Steroid Premedication on Bone Metabolism in Gastrointestinal Cancer (ESPRESSO‐01)

This study is an evaluation of the effect of gastrointestinal cancer chemotherapy with short‐term periodic steroid premedication on bone metabolism. Primary endpoints were changes in bone mineral densities and metabolic bone turnover 16 weeks after initiation of chemotherapy.