Prognostic Value of Serum Albumin in Aortic Aneurysm Patients Undergoing Graft Replacement of Ascending Aorta and Aortic Arch.

Background: Hypoalbuminemia is a marker of poor overall health with influences from protein energy malnutrition, systemic inflammation and hepatic and renal disease. Albumin has been reported to have a prognostic impact in various cohorts. This study investigated whether preoperative serum albumin levels could be used to predict mortality in patients with aortic aneurysms undergoing graft replacement of ascending aorta and aortic arch. Methods: We retrospectively reviewed 183 patients who underwent graft replacement of ascending aorta and aortic arch between January 2010 and December 2020. The exclusion criteria included patients with traumatic aortic injuries (n=2), previous aortic repair within 6 months (n=2), ruptured aortic aneurysms (n=14), or a lack of preoperative laboratory data or medical records (n=10). The remaining 87% eligible patients were divided into two groups based on their preoperative serum albumin levels. The lower albumin group was defined as having serum albumin levels ≤3.5 g/dL, while the higher albumin group was defined as having albumin levels >3.5 g/dL. The incidence of mortality was compared between the two groups, and a logistic regression analysis was performed to evaluate the predictors of mortality. Results: The incidence of 1-year mortality was higher in the lower albumin group than in the higher albumin group (3.4% vs. 23.5%, p=0.006). The optimal cut-off value of albumin to predict 1-year mortality was 4.0 g/dL (area under the curve 0.885, 95% CI 0.821-0.949, p<0.001), with a sensitivity and specificity of 90.0% and 80.3%, respectively. Preoperative serum albumin levels (OR = 0.116, 95% CI 0.021-0.641, p=0.014) and diabetes mellitus (OR = 5.757, 95% CI 1.018-32.565, p=0.048) remained independent predictors of mortality. Conclusion: Preoperative serum albumin levels were an independent predictor of 1-year mortality after the graft replacement of ascending aorta and aortic arch. These findings underscore that the optimization of patients' nutritional status before surgery may be warranted and should be further explored in this high-risk population.

Pericapsular Nerve Group (PENG) Block versus Supra-Inguinal Fascia Iliaca Compartment Block for Total Hip Arthroplasty: A Randomized Clinical Trial.

This study compared the effects of the pericapsular nerve group (PENG) block and supra-inguinal fascia iliaca compartment block (FICB) on postoperative analgesia and quadriceps strength following total hip arthroplasty under general anesthesia. A total of 58 patients were randomized to receive either PENG block (PENG group) or supra-inguinal FICB (FICB group) following anesthetic induction. The primary outcomes were the postoperative pain scores. Patients were randomized to receive either PENG block or supra-inguinal FICB following anesthetic induction. Pain scores at rest and with movement were assessed preoperatively, at the postanesthesia care unit (only at rest), and at 6, 24, 36, and 48 h postoperatively. Opioid consumption was also assessed for 48 h postoperatively. Quadriceps strength measurements were performed preoperatively, at 6, 24, and 36 h postoperatively. In total, 54 patients completed the study: 27 in the PENG group and 27 in the FICB group. Despite lower pain scores at rest in the PENG group at postoperative 6 and 24 h, there were no significant differences in the pain scores at rest and during movement between the two groups during postoperative 48 h in the linear mixed model analysis (p = 0.079 and p = 0.323, respectively). Cumulative opioid consumption up to postoperative 48 h was also similar in the two groups (p = 0.265). The changes in quadriceps strength measurements in the operative leg and the nonoperative leg were not significantly different between the groups (p = 0.513 and p = 0.523, respectively). The PENG block may have similar analgesic efficacy to the supra-inguinal FICB. No difference was detected in the quadriceps strength between the patients receiving these two blocks.

Ability of Carotid Corrected Flow Time to Predict Fluid Responsiveness in Patients Mechanically Ventilated Using Low Tidal Volume after Surgery.

Predicting fluid responsiveness in patients under mechanical ventilation with low tidal volume (VT) is challenging. This study evaluated the ability of carotid corrected flow time (FTc) assessed by ultrasound for predicting the fluid responsiveness during low VT ventilation. Patients under postoperative mechanical ventilation and clinically diagnosed with hypovolemia were enrolled. Carotid FTc and pulse pressure variation (PPV) were measured at VT of 6 and 10 mL/kg predicted body weight (PBW). FTc was calculated using both Bazett's (FTcB) and Wodey's (FTcW) formulas. Fluid responsiveness was defined as a ≥15% increase in the stroke volume index assessed by FloTrac/Vigileo monitor after administration of 8 mL/kg of balanced crystalloid. Among 36 patients, 16 (44.4%) were fluid responders. The areas under the receiver operating characteristic curves (AUROCs) for the FTcB at VT of 6 and 10 mL/kg PBW were 0.897 (95% confidence interval [95% CI]: 0.750-0.973) and 0.895 (95% CI: 0.748-0.972), respectively. The AUROCs for the FTcW at VT of 6 and 10 mL/kg PBW were 0.875 (95% CI: 0.722-0.961) and 0.891 (95% CI: 0.744-0.970), respectively. However, PPV at VT of 6 mL/kg PBW (AUROC: 0.714, 95% CI: 0.539-0.852) showed significantly lower accuracy than that of PPV at VT of 10 mL/kg PBW (AUROC: 0.867, 95% CI: 0.712-0.957; p = 0.034). Carotid FTc can predict fluid responsiveness better than PPV during low VT ventilation. However, further studies using automated continuous monitoring system are needed before its clinical use.

The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial.

BACKGROUND: Blood levels of voriconazole, a first line therapy for invasive aspergillosis, may correlate with adverse events and treatment response. However, no randomized controlled studies have been conducted to evaluate the clinical utility of routine therapeutic drug monitoring (TDM) of voriconazole. This study aimed to determine whether routine TDM of voriconazole reduces drug adverse events or improves treatment response in invasive fungal infections. METHODS: This was a randomized, assessor-blinded, controlled, single center trial. One hundred ten adult patients were randomly assigned to TDM or non-TDM groups. In the TDM group, voriconazole dosage was adjusted (target range, 1.0-5.5 mg/L) according to the serum trough level measured on the fourth day after initiation of voriconazole. The non-TDM group received a fixed, standard dosage. Voriconazole-related adverse events were monitored, and treatment response was assessed three months after the initiation of therapy. RESULTS: Baseline characteristics including the CYP2C19 genotype were comparable between the two groups. While the incidence of adverse events was not different between the TDM group and the non-TDM group (both 42%; P = .97), the proportion of voriconazole discontinuation due to adverse events was significantly lower in the TDM group than in the non-TDM group (4% vs 17%; P = .02). A complete or partial response was observed in 81% (30 of 37) of patients in the TDM group compared to 57% (20 of 34) in the non-TDM group (P = .04). CONCLUSIONS: Routine TDM of voriconazole may reduce drug discontinuation due to adverse events and improve the treatment response in invasive fungal infections. CLINICAL TRIAL REGISTRATION: NCT00890708.

The effect of fimasartan, an angiotensin receptor type 1 blocker, on the pharmacokinetics and pharmacodynamics of warfarin in healthy Korean male volunteers: a one-sequence, two-period crossover clinical trial.

BACKGROUND: Fimasartan is an angiotensin II receptor antagonist used to treat hypertension. OBJECTIVE: The aim of this study was to evaluate the effects of fimasartan on the pharmacodynamics and pharmacokinetics of warfarin in healthy volunteers to meet regulatory requirements for drug marketing and labeling in Korea. METHODS: An open-label, 1-sequence, 2-treatment, 2-period crossover study was conducted in healthy male volunteers. The subjects were administered a single-dose of warfarin 25 mg on day 1. After a 7-day washout period, once-daily fimasartan 240 mg was administered every morning from day 8 to day 16. On day 11, warfarin 25 mg was administered concomitantly with fimasartan. Serial blood samples were collected for 144 hours after each warfarin dose. The plasma concentrations of R- and S-warfarin were analyzed by using HPLC-MS/MS, and the pharmacokinetic parameters were estimated by using noncompartmental analysis. The maximal international normalized ratio (INR) and the AUC-INR curve were evaluated to assess warfarin pharmacodynamics. Tolerability was assessed via vital sign measurements, physical examinations, ECGs, clinical laboratory tests, and adverse events. RESULTS: A total of 15 healthy Korean men aged 20 to 39 years (mean [SD], 26.7 [5.1] years) and weighing 60.2 to 85.7 kg (mean, 71.4 [8.3] kg) participated in the study; 12 completed the study. The geometric mean ratios (GMRs [90% CIs]) of C(max) and AUC(0-last) for R-warfarin were 1.06 (0.97-1.16) and 1.07 (1.03-1.12), respectively. For S-warfarin, the GMRs (90% CIs) of C(max) and AUC(0-last) were 1.02 (0.94-1.11) and 0.99 (0.94-1.04). The INR values reached 1.93 (0.31) and 1.96 (0.37) at 36 hours and decreased to <1.2 at 144 hours after warfarin treatment alone and coadministered with fimasartan, respectively. The GMRs (90% CIs) of the maximal INR and AUC-INR curve were 1.01 (0.97-1.05) and 0.98 (0.96-1.01). One (7.7%) of the 13 subjects reported epistaxis during treatment with warfarin alone, and 2 (16.7%) of 12 subjects receiving the combination treatment experienced headache, skin erosion, and an increase in blood creatine phosphokinase. No subjects had an elevated INR >4 or reported any symptoms related to hypotension, including fainting or dizziness. CONCLUSION: Multiple doses of fimasartan did not seem to alter the pharmacodynamics or pharmacokinetics of warfarin in this small, select population of healthy male volunteers.

Effect of CYP2C19 polymorphism on the pharmacokinetics of voriconazole after single and multiple doses in healthy volunteers.

The current study assessed the influence of the CYP2C19 genotype on the pharmacokinetics and tolerability of voriconazole after single and multiple oral doses in healthy volunteers. Six subjects for the CYP2C19 homozygous extensive metabolizer (EMs), 6 for heterozygous extensive metabolizer (HEMs), and 6 for poor metabolizer (PMs) were enrolled, and their CYP2C9, CYP3A5, and MDR1 genotypes were analyzed. After a single intravenous infusion or single and multiple oral doses of 200 mg of voriconazole, plasma concentrations of voriconazole were measured. Bioavailability was not significantly different among the CYP2C19 genotypes. Voriconazole exposure in PMs was approximately 3 times higher compared with EMs after a single intravenous or oral dose. At steady state, the plasma concentration just before the next dosing and area under the concentration-time curve from dosing to the time point of the next dosing for PMs were about 5 times and 3 times higher than EMs, respectively. These results suggest that the CYP2C19 genotype is the major determinant of the wide PK variability of voriconazole.