Lenvatinib Compared with Sorafenib as a First-Line Treatment for Radioactive Iodine-Refractory, Progressive, Differentiated Thyroid Carcinoma: Real-World Outcomes in a Multicenter Retrospective Cohort Study.

Background: Sorafenib and lenvatinib have been widely adopted to treat radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC). However, limited data exist regarding a direct comparison of these tyrosine kinase inhibitors (TKIs). We aimed to evaluate the clinical efficacy and safety of two TKIs as first-line therapy in patients with distant metastatic or locally advanced, progressive, RAI-refractory DTC in real-world practice. Methods: In this multicenter, retrospective cohort study, we evaluated 136 patients with progressive distant metastatic or locally advanced, progressive, RAI-refractory DTC or poorly differentiated thyroid carcinoma (PDTC) who received first-line sorafenib or lenvatinib treatment. The primary outcome was progression-free survival (PFS). We also evaluated the objective response rate, disease-control rate, clinical benefit rate, and safety. Results: The median age of the patients was 68 years, and 35% (47/136) were male. Eighty and fifty-six patients were included in the sorafenib and lenvatinib groups, respectively. The median PFS was 13.3 months [95% confidence interval, CI, 9.9-18.1 months] in the sorafenib group and 35.3 months [CI, 18.2 months to upper limit not reported as the median was not reached] in the lenvatinib group (p = 0.001). A significantly prolonged PFS was observed in the lenvatinib group (compared with the sorafenib group) after adjusting for age, sex, pathology, disease-related symptom, lung-only metastasis, cumulative RAI dose, time from diagnosis, treatment duration, and longest diameter of the target lesion (hazard ratio = 0.34, CI, 0.19-0.60, p < 0.001). The partial response rate was 24% and 59% in the sorafenib and lenvatinib groups, respectively (p < 0.001). More common grade 3-4 adverse events were hypertension (16%, 9/56 vs. 1%, 1/80, p = 0.002) and proteinuria (32%, 18/56 vs. 0%, p < 0.001) in the lenvatinib group, and hand-foot skin reaction (24%, 19/80 vs. 4%, 2/56, p = 0.001) in the sorafenib group. Conclusion: In our study of Asian patients, first-line lenvatinib treatment of metastatic or locally advanced, progressive, RAI-refractory DTC or PDTC was associated with a longer PFS compared with sorafenib. However, severe hypertension and proteinuria were observed more frequently after lenvatinib treatment than after sorafenib treatment.

Comparison of In Vivo Pharmacokinetics and Pharmacodynamics of Vancomycin Products Available in Korea.

PURPOSE: Few studies have been investigated the in vivo efficacy of generic vancomycin products available outside of the United States. In this study, we aimed to compare the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of five generic vancomycin products available in Korea with those of the innovator. MATERIALS AND METHODS: The in vitro vancomycin purity of each product was examined using high-pressure liquid chromatography. Single-dose PK analyses were performed using neutropenic mice. The in vivo efficacy of vancomycin products was compared with that of the innovator in dose-effect experiments (25 to 400 mg/kg per day) using a thigh-infection model with neutropenic mice. RESULTS: Generic products had a lower proportion of vancomycin B (range: 90.3-93.8%) and a higher proportion of impurities (range: 6.2-9.7%) than the innovator (94.5% and 5.5%, respectively). In an in vivo single-dose PK study, the maximum concentration (Cmax) values of each generic were lower than that of the innovator, and the geographic mean area under the curve ratios of four generics were significantly lower than that of the innovator (all p<0.1). In the thigh-infection model, the maximum efficacies of generic products reflected in maximal effect (Emax) values were not significantly different from the innovator. However, the PD profile curves of some generic products differed significantly from that of the innovator in mice injected with a high level of Mu3 (all p≤0.05). CONCLUSION: Some generic vancomycin products available in Korea showed inferior PK and PD profiles, especially in mice infected with hetero-vancomycin-resistant Staphylococcus aureus.

In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis.

The mortality rate associated with Vibrio vulnificus sepsis remains high. An in vitro time-kill assay revealed synergism between tigecycline and ciprofloxacin. The survival rate was significantly higher in mice treated with tigecycline plus ciprofloxacin than in mice treated with cefotaxime plus minocycline. Thus, combination treatment with tigecycline-ciprofloxacin may be an effective novel antibiotic regimen for V. vulnificus sepsis.

Utility and safety of commercially available injection laryngoplasty materials in a rabbit model.

OBJECTIVE: To demonstrate foreign body and chronic inflammatory reaction of commercially available injection materials using the rabbit vocal fold paralysis model. STUDY DESIGN: Animal study. METHODS: The left recurrent laryngeal nerve was identified and divided at the tracheoesophageal groove. Amounts (100 µL) of phosphate-buffered saline (PBS), polyacrylamide hydrogel (Aquamid; Ferrosan A/S, Søborg, Denmark), calcium hydroxyapatite (Radiesse; BioForm Medical Inc., San Mateo, CA), or hyaluronic acid derivative (Rofilan; Rofil Medical International, Breda, Netherlands) were injected into the left vocalis muscle. Six months later, the larynx was harvested. Hematoxylin/eosin and Masson trichrome staining were performed to compare inflammatory and foreign body reactions, granuloma development, and relative vocal fold areas among groups. RESULTS: Compared with the PBS (control) group, the Aquamid, Radiesse, and Rofilan groups exhibited only mild chronic inflammatory reactions that did not significantly differ among groups, or from controls (P > 0.05). However, the Aquamid and Radiesse groups exhibited moderate foreign body reactions that were significantly greater than those of controls (P < 0.05). No foreign body granuloma formed in any group. All test groups exhibited significant increases in vocal fold areas at 6 months (P < 0.05). CONCLUSIONS: Although commercially available injection materials induced more foreign body reactions than a control injection of PBS, no foreign body granuloma developed and the augmented vocal fold area was maintained until 6 months after injection.

Effect of a mind-body therapeutic program for infertile women repeating in vitro fertilization treatment on uncertainty, anxiety, and implantation rate.

PURPOSE: The study aimed to develop a mind-body therapeutic program and evaluate its effects on mitigating uncertainty, anxiety, and implantation rate of second-trial in vitro fertilization (IVF) women. METHODS: This study employed a nonequivalent control group nonsynchronized design. The conceptual framework and program content were developed from a preliminary survey of eight infertile women and the extensive review of the literature. Program focuses on three uncertainty-induced anxieties in infertile women: cognitive, emotional, and biological responses. To evaluate the effect of the intervention, the infertile women with unknown cause preparing for a second IVF treatment were sampled at convenience (26 experimental and 24 control). RESULTS: The experimental group in the study showed greater decrease in uncertainty and anxiety in premeasurements and postmeasurements than the control group did. However, no statistically significant differences in the implantation rate between groups were observed. CONCLUSION: This study is meaningful as the first intervention program for alleviating uncertainty and anxiety provided during the IVF treatment process. The positive effects of the mind-body therapeutic program in alleviating both uncertainty and anxiety have direct meaning for clinical applications.

In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.

OBJECTIVES: The in vivo efficacy of a cefotaxime-ciprofloxacin combination against Vibrio vulnificus and the effects on rtxA1 expression of commonly used antibiotics are unknown. METHODS: In vitro time-kill studies were performed to evaluate synergism. Female BALB/c mice were injected subcutaneously with 1×10(7) or 1×10(8) cfu of V. vulnificus. Antibiotic therapy was initiated at 2 h after inoculation in the following four therapy groups: cefotaxime; ciprofloxacin; cefotaxime-plus-ciprofloxacin; and cefotaxime-plus-minocycline. The cytotoxicity of V. vulnificus for HeLa cells was measured using the lactate dehydrogenase assay; rtxA1 transcription was measured in a transcriptional reporter strain using a ß-galactosidase assay. RESULTS: In vitro time-kill assays exhibited synergism between cefotaxime and ciprofloxacin. In the animal experiments, the 96-h survival rate for the cefotaxime-plus-ciprofloxacin group (85%; 17/20) was significantly higher than that of the cefotaxime-plus-minocycline (35%; 7/20) and cefotaxime alone (0%; 0/20) groups (P<0.05 for both). Bacterial counts in the liver and spleen were significantly lower in the cefotaxime-plus-ciprofloxacin group 24 and 48 h after treatment, relative to the other groups. At sub-inhibitory concentrations, ciprofloxacin inhibited more effectively rtxA1 transcription and mammalian cell cytotoxicity than either minocycline or cefotaxime (P<0.05 for both). CONCLUSIONS: Ciprofloxacin is more effective at reducing rtxA1 transcription and subsequent cytotoxicity than either minocycline or cefotaxime, and the combination of ciprofloxacin and cefotaxime was more effective in clearing V. vulnificus in vivo than previously used regimens. These data suggest that the combination of ciprofloxacin and cefotaxime is an effective option for the treatment of V. vulnificus sepsis in humans.

[Effectiveness of forgiveness therapy on resilience, self-esteem, and spirituality of wives of alcoholics].

PURPOSE: In this study the effects of forgiveness therapy on the resilience, self-esteem, and spirituality of wives of men suffering from alcohol abuse was examined. METHODS: The study design was a quasi-experimental design. Forgiveness therapy was conducted once a week for 12 weeks. Data were obtained from March 2012 to December 2013. Participants were chosen from women in two Alcohol Counseling Centers. Of the 29 participants, 16 were assigned to the experimental group and 13 to the control group. Data were analyzed using descriptive statistics, t-test, χ(2)-test, and repeated measure ANOVA. RESULTS: There were statistically significantly differences for resilience, self-esteem, and spirituality between the experimental and control groups. Forgiveness therapy improved the resilience, self-esteem, and spirituality in the experimental group compared to the control group (p<.05). In follow-up tests, the experimental group had a statistically significantly increase only in self-esteem. CONCLUSION: This study results show that forgiveness therapy is effective in improving resilience, self-esteem, and spirituality in wives of men suffering from alcohol abuse. Therefore, forgiveness therapy can be considered a useful nursing intervention to promote improvements in emotional stability and provide pain relief for these wives.

Quantitative assessment of the T2 relaxation time of the gluteus muscles in children with Duchenne muscular dystrophy: a comparative study before and after steroid treatment.

OBJECTIVE: To determine the feasibility of using T2 mapping as a quantitative method to longitudinally follow the disease activity in children with Duchenne muscular dystrophy (DMD) who are treated with steroids. MATERIALS AND METHODS: ELEVEN BOYS WITH DMD (AGE RANGE: 5-14 years) underwent evaluation with the clinical functional score (CFS), and conventional pelvic MRI and T2 mapping before and during steroid therapy. The gluteus muscle inflammation and fatty infiltration were evaluated on conventional MRI. The histograms and mean T2 relaxation times were obtained from the T2 maps. The CFS, the conventional MRI findings and the T2 values were compared before and during steroid therapy. RESULTS: None of the patients showed interval change of their CFSs. On conventional MRI, none of the images showed muscle inflammation. During steroid treatment, two boys showed increased fatty infiltration on conventional MRI, and both had an increase of the mean T2 relaxation time (p < 0.05). The remaining nine boys had no increase in fatty infiltration. Of these, three showed an increased mean T2 relaxation time (p < 0.05), two showed no change and four showed a decreased mean T2 relaxation time (p < 0.05). CONCLUSION: T2 mapping is a feasible technique to evaluate the longitudinal muscle changes in those children who receive steroid therapy for DMD. The differences of the mean T2 relaxation time may reflect alterations in disease activity, and even when the conventional MRI and CFS remain stable.