Evaluation of PLGA microspheres with triple regimen on long-term survival of vascularized composite allograft - an experimental study.

Systemic immunosuppression is indispensable for vascularized composite allotransplantation (VCA). Daily administration of standard triple therapy regimen of tacrolimus (FK506), mycophenolate mofetil (MMF), and steroid has severe side effects and reduces the compliance of VCA recipients. To overcome these hurdles, FK506/MMF/prednisolone (PDNN) was loaded into PLGA microspheres (PGLA MS). A single injection of FK506/MMF/PDNN-PLGA MS significantly prolonged the survival time of allograft in a rat hind limb transplantation model with a median survival time (MST) of more than 150 days compared to 34.5 days in the group treated orally with FK506/MMF/PDNN and 11 days in the nontreatment allograft and MS control groups. Analysis of showed that FK506/MMF/PDNN-PLGA MS could maintain relatively higher plasma and tissue drug concentrations for a long time. Moreover, histopathology and flow cytometry of circulating mononuclear cells revealed significantly prolonged immunosuppression by the FK506/MMF/PDNN-PLGA MS compared with the orally given FK506/MMF/PDNN. In conclusion, a single injection of FK506/MMF/PDNN-PLGA MS may provide a new approach for long-term prevention of immune rejection in VCA.

Study on the clinical efficacy of 14-day vonoprazan-based triple regimen in obese patients with Helicobacter pylori infection.

The effectiveness of vonoprazan (VPZ)-based regimens in enhancing Helicobacter pylori (HP) eradication rates is promising. This study evaluated the clinical efficacy of 14-day VPZ-based triple therapy in obese patients infected with HP. A total of 200 obese patients with gastric disorders, confirmed to be HP-positive via gastroscopy and the 13C urea breath test, were retrospectively analyzed. Among them, 118 patients received the 14-day VPZ-based triple regimen (Study group), while 82 patients were treated with the traditional 14-day bismuth-containing proton pump inhibitor-based quadruple regimen (Control group). Baseline characteristics, pretreatment inflammatory indicators, lipid profiles, and gastrointestinal function indicators recorded. The two groups were compared for treatment efficacy, HP eradication rate, gastrointestinal function improvement, and incidence of adverse reactions. The Study group demonstrated a higher overall effective rate compared to the Control group, particularly in HP-strong positive obese patients. No significant differences were observed between the two groups for HP-positive obese patients in terms of total effective rate, HP eradication rate, gastrointestinal function improvement, or adverse reactions incidence. In conclusion, the 14-day VPZ-based triple regimen exhibited superior therapeutic efficacy, higher HP eradication rates, enhanced gastrointestinal function, and reduced adverse reactions in HP-strong positive obese patients, indicating improved overall efficacy and safety.

The 14-d VPZ-based triple regimen is effective in HP-infected obese patients.The 14-d VPZ-based triple regimen has a high total effective rate in HP-strong positive-infected obese patients.The 14-d VPZ-based triple regimen has a high HP eradication rate in HP-strong positive-infected obese patients.The 14-d VPZ-based triple regimen has good improvement on the gastrointestinal function of HP-strong positive-infected patients.The 14-d VPZ-based triple regimen has low adverse reaction incidence in HP-strong positive-infected obese patients.

[Short-term intensive combined therapy with metformin, sagliptin and dapagliflozin for newly diagnosed type 2 diabetes: efficacy, weight control and safety].

OBJECTIVE: To assess the efficacy and safety of short- term intensive hypoglycemic therapy with a triple regimen consisting of metformin, sagliptin and dapagliflozin in patients with newly diagnosed type 2 diabetes mellitus with hemoglobin Alc (HbA1c) of 9%-12%. METHODS: We prospectively enrolled 58 patients with newly diagnosed type 2 diabetes, who were treated with metformin combined with sagliptin and dapagliflozin for 12 weeks on the basis of diabetic diet and regular exercise. Blood glucose was monitored during the treatment and the changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 hPBG), fasting insulin (FINS), 2-hour postprandial insulin (2 hPINS), fasting C-peptide (F-CP), 2-hour postprandial C-peptide (2 hP-CP), and body weight after treatment as well as the incidence of hypoglycemia and adverse events associated with the treatment were recorded. RESULTS: Two patients withdrew from the study for intolerance of gastrointestinal reactions, and another 2 withdrew for inconvenience of access to the medicines. Fifty-four of the patients finally completed the study, including 34 male and 20 female patients. After 12 weeks of therapy, all the patients showed significant improvements in FBG, 2 hPBG, HbA1c, HOMA-beta and HOMA-IR (P < 0.001) with a mean reduction of HbA1c level by (4.19 ± 1.07)%, and the goal of HbA1c control to below 7.0% was achieved in 83.33% of the patients. The reduction of HbA1c was correlated with FBG (r=0.487, P=0.000), 2 hPBG (r=0.310, P=0.023), and HOMA-ß (r=-0.398, P=0.003). The patients had a mean body weight loss by 2.47±3.38 kg (P < 0.001) and a mean decrease of body mass index (BMI) by 0.90± 1.18 kg/m2 (P < 0.001) after the therapy. The body weight-reducing effect was associated with the patients' baseline body weight (r=0.678, P=0.000), BMI (r=0.818, P=0.000), F-CP (r=0.282, P=0.039) and HOMA-IR (r=0.297, P=0.029). During the therapy 8 patients experienced hypoglycemic symptoms (10 times, 14.81%); 3 patients were diagnosed with hypoglycemia (blood glucose ≤3.9 mmol/L, 3 times), and the overall incidence of hypoglycemia was 5.56%. No serious hypoglycemia or infections of the urinary and reproductive systems occurred in these patients. CONCLUSIONS: Short-term intensive oral hypoglycemic therapy with metformin combined with sagliptin and dapagliflozin is effective for treatment of patients with newly diagnosed type 2 diabetes with HbA1c of 9%-12% and shows a good weight-reducing effect with a low risk of hypoglycemia. The combined therapy can effectively improve ß-cell insulin secretion function, and is suitable for treatment of newly diagnosed type 2 diabetic patients with high blood glucose.

Efficacy of 7-Day and 14-Day Bismuth-Containing Quadruple Therapy and 7-Day and 14-Day Moxifloxacin-Based Triple Therapy as Second-Line Eradication for Helicobacter pylori Infection.

BACKGROUND/AIMS: Bismuth-containing quadruple and moxifloxacin-based triple regimens are recommended as second-line therapy for Helicobacter pylori infection. The aim of this study was to compare the efficacy of each regimen. METHODS: From August 2004 to October 2012, a total of 949 patients (mean age, 54.32±12.08 years; male, 49.4%) who failed H. pylori eradication with a standard triple regimen were included. Patients treated with a bismuth-containing quadruple regimen for 7 and 14 days were designated as 7-BMT and 14-BMT, respectively, and those treated with a moxifloxacin-based triple regimen for 7 and 14 days were designated as 7-MA and 14-MA, respectively. H. pylori eradication was confirmed using the (13)C-urea breath test, rapid urease test or histology. RESULTS: The eradication rates by 7-BMT, 14-BMT, 7-MA, and 14-MA were 66.4% (290/437), 71.1% (113/159), 53.1% (51/96), and 73.5% (189/257), respectively, by intention-to-treat analysis (ITT) and 76.5% (284/371), 83.8% (109/130), 55.6% (50/90), and 80.6% (187/232), respectively, by per-protocol analysis (PP). The eradication rates were higher in 14-BMT than 7-BMT by the ITT and PP analyses (p=0.277 and p=0.082, respectively). The 14-BMT and 14-MA treatments showed similar efficacies by ITT and PP (p=0.583 and p=0.443, respectively). CONCLUSIONS: The 7-BMT, 14-BMT, and 14-MA treatments showed similar and suboptimal efficacies. In both regimens, extending the duration of treatment may be reasonable considering the high level of antibiotic resistance in Korea.