Impact of Controlling a Nutritional Status Score on Wound Healing in Patients with Chronic Limb-Threatening Ischemia after Endovascular Treatment.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral artery disease. Therefore, a multidisciplinary approach is necessary to avoid major amputation in CLTI patients. Malnutrition worsens the condition of CLTI patients, and therefore, it may be important to evaluate the nutritional status in patients with CLTI. This study was designed to evaluate the baseline patient characteristics and the influence of the controlling nutritional status (CONUT) score on the clinical results. METHOD AND RESULTS: A retrospective, single-center, non-randomized study was conducted to evaluate the associations of death, major amputation, and wound healing rate at 12 months with the CONUT score on admission. Consecutive CLTI patients (mean age 73.2 ± 10.4 years; 84 males) who underwent endovascular therapy (EVT) for infra-popliteal lesions at Fukuoka University Hospital from January 2014 to May 2019 were enrolled and divided into two groups (higher and lower CONUT score groups). The higher CONUT group showed a higher percentage of dialysis (66.7% vs. 33.9%, p < 0.001) and a higher clinical frailty scale (5.9 ± 1.4 vs. 4.9 ± 1.9, p = 0.005) than the lower CONUT group. Rates of amputation-free survival were 89.5% and 69.8% in the lower and higher CONUT groups, respectively. In addition, rates of wound healing at 12 months were 98.0% and 78.3% in the lower and higher CONUT groups, respectively. Multivariate regression analysis demonstrated that a higher CONUT score was an independent predictor for delayed wound healing (OR: 11.2; 95% CI: 1.29-97.5; p = 0.028). CONCLUSION: An assessment of the nutritional status using the CONUT score could be useful for predicting wound healing, and earlier nutritional intervention may improve the outcome of CLTI patients. Early examination and treatment, along with raising awareness of the issue, may be important for improving the prognosis.

Efficacy and Safety of Combination Therapy Consisting of Angiotensin II Type 1 Receptor Blocker, Calcium Channel Blocker and Hydrochlorothiazide in Patients With Hypertension.

BACKGROUND: Many patients continue to have high blood pressure (BP) even after treatment with high-dose (H)-angiotensin II type 1 receptor blocker (ARB)/calcium channel blocker (CCB) or middle-dose (M)-ARB/CCB/hydrochlorothiazide (HCTZ). METHODS: Thirty-two hypertensive patients who had the use of H-ARB/CCB or M-ARB/CCB/HCTZ were enrolled in this study. We applied a changeover with a switch to H-ARB (telmisartan 80 mg/day)/CCB (amlodipine 5 mg/day or nifedipine CR 40 mg/day)/HCTZ (12.5 mg/day). RESULTS: Systolic BP (SBP) and diastolic BP (DBP) were significantly decreased in all patients and in the H-ARB/CCB and M-ARB/CCB/HCTZ groups after 3 months. Percentage (%) of patients who reached the target BP after 3 months (72%) in all patients was significantly higher than that at 0 months (19%). There were no serious adverse effects in any of the patients. CONCLUSIONS: Combination therapy with H-ARB/CCB/HCTZ was associated with a significant reduction of BP.

Evaluation of the antithrombotic abilities of non-vitamin K antagonist oral anticoagulants using the Total Thrombus-formation Analysis System®.

The Total Thrombus-formation Analysis System (T-TAS®) is a novel automated microchip flow-chamber system for the quantitative evaluation of thrombus formation under blood flow conditions. T-TAS® uses two types of microchip to evaluate thrombus formation: the AR-chip quantifies white thrombus formation and the PL-chip quantifies platelet thrombus formation. We assessed the antithrombotic abilities of various non-vitamin K antagonist oral anticoagulants (NOACs) using T-TAS®. One hundred and three consecutive patients who were hospitalized with cardiovascular diseases were enrolled. We divided the patients into 2 groups; a control group that did not receive an anticoagulant (non-AC group) and an anticoagulant group (AC group). The AC group was further divided into warfarin, dabigatran, rivaroxaban and apixaban groups. We performed common coagulation tests and evaluated the area under the flow pressure curve (AR-AUC and PL-AUC) to quantify antithrombotic ability using T-TAS® at the trough. There were no significant differences in patient characteristics between the non-AC and AC groups. Only 55.1 % of patients in the AC group achieved the target blood pressure (BP) of less than 130/80 mmHg. Compared with the non-AC group, AR-AUC was significantly decreased in the AC, warfarin, dabigatran and apixaban groups. Only the rivaroxaban group did not show a significant decrease in AR-AUC. NOACs showed a significant decrease in PL-AUC compared with the non-AC group. In conclusion, T-TAS® was a useful tool for evaluating anticoagulation activity. NOACs was significantly effective as an antiplatelet agent. BP control should be a higher priority than the selection of an anticoagulant drug, especially NOACs.

Efficacy and safety of combination therapy of high-dose losartan and hydrochlorothiazide in patients with hypertension.

OBJECTIVE: We analyzed the efficacy and safety of combination therapy of high-dose losartan (100 mg/day) and hydrochlorothiazide (HCTZ, 12.5 mg/day) compared with those of the combination of high-dose telmisartan (80 mg/day) and HCTZ (12.5 mg/day). METHODS: Forty hypertensive patients who received a combination of high-dose telmisartan and HCTZ were enrolled. We applied a changeover strategy with switching from a combination of high-dose telmisartan and HCTZ to high-dose losartan and HCTZ. We divided the patients into two groups; those who achieved the target blood pressure (controlled group) and those who did not reach the target blood pressure (uncontrolled group) before the changeover and performed further analysis. RESULTS: The uncontrolled group showed a significant decrease in systolic blood pressure (SBP) (143±12 mmHg to 126±11 mmHg at three months). In addition, serum uric acid significantly decreased in all subjects, and in each of the controlled and uncontrolled groups. There were no significant changes in other biochemical parameters, such as potassium and hemoglobin A1c, at three months after the changeover in all subjects. CONCLUSION: Combination therapy with high-dose losartan and HCTZ was superior to the combination of telmisartan and HCTZ with respect to significant decreases in systolic blood pressure and serum uric acid in hypertensive patients.

Lipidomic analyses of female mice lacking hepatic lipase and endothelial lipase indicate selective modulation of plasma lipid species.

Hepatic lipase (HL) and endothelial lipase (EL) share overlapping and complementary roles in lipoprotein metabolism. The deletion of HL and EL alleles in mice raises plasma total cholesterol and phospholipid concentrations. However, the influence of HL and EL in vivo on individual molecular species from each class of lipid is not known. We hypothesized that the loss of HL, EL, or both in vivo may affect select molecular species from each class of lipids. To test this hypothesis, we performed lipidomic analyses on plasma and livers from fasted female wild-type, HL-knockout, EL-knockout, and HL/EL-double knockout mice. Overall, the loss of HL, EL, or both resulted in minimal changes to hepatic lipids; however, select species of CE were surprisingly reduced in the livers of mice only lacking EL. The loss of HL, EL, or both reduced the plasma concentrations for select molecular species of triacylglycerol, diacylglycerol, and free fatty acid. On the other hand, the loss of HL, EL, or both raised the plasma concentrations for select molecular species of phosphatidylcholine, cholesteryl ester, diacylglycerol, sphingomyelin, ceramide, plasmanylcholine, and plasmenylcholine. The increased plasma concentration of select ether phospholipids was evident in the absence of EL, thus suggesting that EL might exhibit a phospholipase A2 activity. Using recombinant EL, we showed that it could hydrolyse the artificial phospholipase A2 substrate 4-nitro-3-(octanoyloxy)benzoic acid. In summary, our study shows for the first time the influence of HL and EL on individual molecular species of several classes of lipids in vivo using lipidomic methods.

Efficacy and safety of a single-pill fixed-dose combination of high-dose telmisartan/hydrochlorothiazide in patients with uncontrolled hypertension.

OBJECTIVE: Many patients still have high blood pressure (BP) after treatment with high-dose angiotensin II type 1 receptor blockers (ARBs) or Preminent® (medium-dose of losartan (50 mg/day)/hydrochlorothiazide (HCTZ) (12.5 mg/day)). Therefore, we analyzed whether Micombi®BP (high-dose telmisartan (80 mg/day)/HCTZ (12.5 mg/day)) could provide better results with regard to efficacy and safety for patients with uncontrolled hypertension. METHODS: In total, 44 hypertensive patients (22 males, age 71±14 years) who showed uncontrolled BP despite the use of high-dose ARBs or Preminent® were enrolled in this study. We used a changeover design in which the patients were switched from high-dose ARBs or Preminent® to Micombi®BP. We analyzed BP, heart rate (HR), and biochemical parameters before and after treatment for 3 months. RESULTS: Systolic BP and diastolic BP significantly decreased (125±15/69±11 mmHg) and 85% of the patients achieved their target BP at 3 months after changeover. Patients who switched from ARBs and those who switched from Preminent® showed similar BP-lowering effects. In addition, the reductions in BP after 3 months in patients with or without chronic kidney disease and in those with or without metabolic syndrome (MetS) were also similar. There were no significant changes in HR during the study period. Although blood levels of potassium, hemoglobin A1c and uric acid (UA) significantly increased after 3 months for all of the patients, none of the patients showed serious adverse effects. CONCLUSION: High-dose telmisartan/HCTZ therapy was associated with a significant reduction in BP and helped patients achieve their target BP.

Radiosynthesis and in vivo evaluation of 11C-labeled 1,5-diarylpyrazole derivatives for mapping cyclooxygenases.

We prepared 11C-labeled 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole ([11C]1) and 4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-pyrazol-1-yl]benzenesulfonamide ([11C]2) for imaging COX-1 and COX-2 isoforms, respectively, by positron emission tomography. [11C]1 and [11C]2 were synthesized in high radiochemical yields by O-[11C]methylation with [11C]methyl triflate in acetone containing an equivalent of NaOH as a base with respect to the phenolic precursors. In vivo evaluation in rats bearing AH109A hepatoma demonstrated minimal specific binding of [11C] to COX-1 in peripheral organs, such as the spleen and small intestine. Carrier-saturable uptake of [11C]2 was found in the spleen, but COX-2-specific binding of [11C]2 was not identifiable in the brain, AH109A hepatoma or other peripheral organs, although ex vivo autoradiography showed regionally different distribution in the brain and AH109A. The results suggest that neither [11C]1 nor [11C]2 is a suitable radioligand for in vivo biomarkers of COX enzymes, mainly because of marked non-specific binding.