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Plasma daptomycin has not been fully characterized in diabetic and obese patients. This study aimed to evaluate the associations of plasma daptomycin with glycation of serum albumin and obesity.Infectious patients (n = 70) receiving intravenous daptomycin were enrolled. The plasma concentration of total and free daptomycin were determined using liquid chromatograph-tandem mass spectrometer. The associations of the plasma concentrations of daptomycin with clinical factors including serum albumin fractionations and physical status (obese including overweight, body mass index ≥ 25.0) were investigated. Daptomycin doses were adjusted using total body-weight.The serum albumin level was positively and negatively correlated with the plasma concentration of total daptomycin and its free fraction proportion, respectively. The serum non-glycated albumin was negatively correlated with the free fraction proportion. The dose-normalized plasma concentration of total daptomycin was higher in the obese patients than in non-obese patients when the body-weight was corrected with total and adjusted values. For the dose adjustment with lean body-weight, no difference was observed in the dose-normalized plasma concentration of total daptomycin between the physical statuses. For each body-weight correction method, physical status did not affect the dose-normalized plasma concentration of free daptomycin.The glycation of serum albumin and obesity did not associate with dose-normalized plasma free daptomycin. In obese patients, daptomycin dosage adjustment with total body-weight and adjusted body-weight may lead to an apparent excessive exposure resulting in overdosage compared to lean body-weight.

Rotator cuff retear is a major concern after arthroscopic rotator cuff repair (ARCR); however, the effects of retear remain unclear. Therefore, the purpose of this study was to assess the clinical outcomes of postoperative retear and intact tendons after ARCR.We searched PubMed, Cochrane Library, Scopus, and PEDro databases for studies performed from January 2000 to June 2020. Clinical outcomes included the Constant score, American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles shoulder (UCLA) score, pain score, range of motion, and muscle strength. Meta-analysis using random-effects models was performed on the pooled results to determine significance.The initial database search yielded 3141 records. After removal of duplicates, 26 of which met the inclusion criteria. Patients in the retear group had significantly lower Constant score [- 8.51 points (95% CI, - 10.29 to - 6.73); P 0.001], ASES score [- 12.53 points (95% CI, - 16.27 to - 8.79); P 0.001], UCLA score [- 3.77 points (95% CI, - 4.72 to - 2.82); P 0.001], and significantly higher pain score [0.56 cm (95% CI, 0.10 to 1.01); P = 0.02] than the intact group. In addition, the retear group had significantly lower flexion [- 10.46° (95% CI, - 19.86 to - 1.07); P = 0.03], abduction [- 14.84° (95% CI, - 28.55 to - 1.14); P = 0.03], and external rotation [- 7.22° (95% CI, - 13.71 to - 0.74); P = 0.03] range of motion, and flexion [- 1.65 kg·f (95% CI, - 2.29 to - 1.01); P 0.001], abduction [- 1.87 kg·f (95% CI, - 3.02 to - 0.72); P = 0.001], and external rotation [- 1.66 kg·f (95% CI, - 3.25 to - 0.07); P = 0.04] muscle strength.Our results suggest that retear after ARCR leads to poor clinical outcomes after surgery.

The diuretic effect of tolvaptan is largely blood level-dependent although it does exhibit interindividual differences according to cytochrome P450 (CYP) 3A5 genotype. This study aimed to investigate the pharmacokinetic relationship between plasma tolvaptan and its monohydroxylate enantiomers and the factors affecting their metabolism in heart failure patients.Japanese heart failure patients (n = 88) receiving oral tolvaptan (median dosage 7.5 mg/day) were enrolled. Blood samples were collected prior to the dosing on day 6 or later after first administration to determine the plasma concentrations of tolvaptan and its monohydroxylate enantiomers. Gene polymorphisms of CYP3A5, carbonyl reductase (CBR) 1/3, and ATP-binding cassette subfamily B member (ABCB) 1 were analyzed for their impact on tolvaptan pharmacokinetics. Serum laboratory test values and concomitant use of amiodarone were evaluated as factors related to tolvaptan metabolism.The median of the sum of the 5S- and 5R-tolvaptan plasma concentrations was 48.9 (range, 15.3-100) ng/mL. CYP3A5 genotypes significantly affected the concentration ratio of all enantiomeric metabolites to tolvaptan, while the other metabolic-related gene polymorphisms had no influence. A negative correlation was found between serum albumin and the enantiomeric ratio of tolvaptan and monohydroxylate DM-4111. Concomitant use of amiodarone increased the plasma levels of whole tolvaptan but significantly decreased the metabolic ratios of 5R-tolvaptan. 5S-tolvaptan was selectively synthesized from ketone MOP-21826 by CBR1 with a substantially smaller reaction velocity compared to tolvaptan monohydroxylation by CYP3A4/5.This study clarified the racemic impact of CYP3A5 genotypes on tolvaptan metabolism. Amiodarone may stereoselectively interact with R-forms rather than S-forms of tolvaptan.

Wheelchair basketball athletes have increased upper limb stress, which frequently leads to shoulder pain.The purpose of this scoping review was to summarize the existing literature on shoulder pain in wheelchair basketball athletes.We searched PubMed, Cochrane Library, Scopus, and PEDro databases for studies performed between January 1990 and February 2021. Two independent reviewers screened the studies according to the inclusion and exclusion criteria. Participants' characteristics and results were extracted from the study.The initial database search yielded 2455 articles, 11 of which met the inclusion criteria. This review included seven studies in its final analysis; among them, seven determined the prevalence and incidence of shoulder pain, five investigated the factors and mechanisms contributing to shoulder pain, and two reported the treatment and preventive measures. The prevalence of shoulder pain in wheelchair basketball players ranged from 38%-75%, and the incidence of shoulder pain was 14%. Factors/mechanisms included overuse, decreased trunk control, and driving posture. Treatment/preventive measures consisted of shoulder and scapular muscle strengthening and stretching exercises. However, the literature on treatment/prevention was scarce, and its effectiveness was unclear.This scoping review confirmed the high prevalence of shoulder pain in wheelchair basketball players; despite this, studies regarding treatment or preventive measures remain lacking. Further studies investigating the mechanism of onset of shoulder pain and the effectiveness of therapeutic and preventive measures are needed in the future.

Long-term use of itraconazole (ITZ) is associated with a risk of inducing hepatotoxicity. This study aimed to evaluate the associations of plasma concentrations of ITZ and its hydroxylated metabolite (OH-ITZ) with endogenous markers of hepatic function.Thirty six patients treated with oral ITZ solution for prophylaxis of deep mycosis were enrolled. Plasma concentrations of ITZ and OH-ITZ were determined on the 14th day or later after administration of ITZ. Their associations with endogenous marker levels of hepatic function including plasma coproporphyrin (CP)-I and OATP1B1 genotypes were assessed.The serum level of total bilirubin (T-Bil) was moderately correlated with the plasma concentration of total ITZ (tITZ) and OH-ITZ (tOH-ITZ). T-Bil elevation above 0.3 mg/dL was observed in 19% of patients, although statistically significant difference was not identified. The plasma concentration of tITZ had no correlation with other endogenous markers levels including AST, ALT, albumin, and plasma CP-I. The serum AST and plasma CP-I levels were correlated with the plasma concentration of free OH-ITZ (fOH-ITZ). T-Bil and plasma CP-I, a marker of OATP1B1 activity, were not correlated with each other, and neither was associated with the OATP1B1 genotypes.Plasma ITZ and OH-ITZ had a positive association with T-Bil. The patients with a higher fOH-ITZ level had lower OATP1B1 activity on the basis of plasma CP-I level. ITZ and OH-ITZ have the potential to slightly increase endogenous marker levels of hepatic function, although most likely by different mechanisms.

Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia progression and clinical responses in head and neck cancer patients. Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Serum albumin level was negatively correlated with the plasma concentrations of aprepitant at 24 hours after a 3-day aprepitant treatment. The patients with Glasgow Prognostic Score (GPS) 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9 ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant. In conclusion, cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant.