Minimum-Dose,Short-Term Methotrexate With Tacrolimus for Graft-vs-Host Disease Prophylaxis Following Unrelated Cord Blood Transplantation in Adults: A Retrospective Analysis at a Single Institution

BackgroundMethotrexate (MTX) or mycophenolate mofetil with tacrolimus (TAC) is used for graft-vs-host disease (GVHD) prophylaxis in unrelated cord blood transplantation (CBT). However, there is no consensus regimen for GVHD prophylaxis in CBT. We aimed to assess the efficacy and feasibility of minimum-dose, short-term MTX (MS-MTX) for GVHD prophylaxis in CBT.MethodsWe retrospectively evaluated 35 consecutive adult patients who underwent CBT and received MS-MTX (6 mg/m² day 1; 3 mg/m² days 3 and 6, intravenously) with TAC for GVHD prophylaxis in our hospital between 2015 and 2019. Transplantation outcomes with respect to time to hematopoietic recovery, engraftment, incidence and severity of GVHD, adverse events, relapse, nonrelapse mortality (NRM), and overall survival were evaluated.ResultsThe median time to neutrophil, platelet, and reticulocyte recovery was 22, 38, and 32 days, respectively. Cumulative neutrophil engraftment was 91.4%. After a median 3.2-year follow-up, the 2-year overall survival was 64.3%. The 2-year cumulative incidence of relapse and NRM was 20.4% and 14.9%, respectively. The 100-day cumulative incidence of grade II-IV acute GVHD and 2-year cumulative incidence of chronic GVHD were 28.6% and 36.6%, respectively. No grade IV acute GVHD was observed. Sixteen patients experienced oral mucositis and/or pharyngeal pain (46%; grades 1-2, n = 15; grade 3 pharyngeal pain, n = 1). No patients suffered from human herpesvirus 6 encephalitis/myelitis.ConclusionsMS-MTX with TAC is feasible and safe and yields lower rates of severe oropharyngeal mucositis and human herpesvirus 6 encephalitis/myelitis without increasing GVHD, graft failure, relapse, or NRM.     

The effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy: A longitudinal analysis (FRARP-QL Study)

ObjectivesWe aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP).Materials and MethodsWe longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP.ResultsThe median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening.ConclusionsFrailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.     

A Simple and Rapid Fluorometric Determination Method of α1-Acid Glycoprotein in Serum Using Quinaldine Red

We examined different fluorescent probes suitable for fluorometric determination of ₁-acid glycoprotein (AGP) in serum. Quinaldine red (QR) was shown to bind strongly and selectively to AGP. Taking advantage of the enhanced fluorescence of QR in the presence of AGP, we developed a direct method for the determination of serum AGP without removal of other serum proteins such as albumin. AGP concentrations in serum of healthy volunteers and patients correlated well with results from the conventional single radial immunodiffusion (SRID) method (r = 0.93, slope = 1). The newly developed method is faster and has a larger analytical concentration range than the SRID method. This method can also be used to determine AGP in serum of experimental animals, and it can serve to monitor AGP serum concentrations for pharmacokinetic evaluation of basic drugs.     

Prolonged antinociceptive effect of poly (DL-lactic acid)-fentanyl composites after their intrathecal injection in rats

We synthesized poly (DL-lactic acid)-fentanyl composites and compared the duration of analgesia after the administration of a single intrathecal dose of these agents in rats. The drug was injected with an intrathecal catheter into the intrathecal space. Fentanyl composites or plain fentanyl in doses of 2.5 or 25 micrograms were administered, respectively. Animals were then tested for analgesia using the tail-flick test. The release rate of fentanyl from fentanyl composites in vitro was also evaluated. The antinociceptive effect of fentanyl composites (25 micrograms) was significantly longer than that of plain fentanyl. Administration of poly (DL-lactic acid) alone did not induce the antinociceptive effect. Four of 7 animals given plain fentanyl (25 micrograms) exhibited temporary respiratory depression, but none of the animals given fentanyl composites showed this response. In vitro experiments demonstrated a slow release of fentanyl from the fentanyl composites. We conclude that the antinociceptive effect of fentanyl can be prolonged when administered as a poly (DL-lactic acid)-fentanyl composite in the intrathecal space with decreased systemic side effects compared with the plain formulation.     

Finger bougie method compared with pyloroplasty in the gastric replacement of the esophagus

To elucidate the necessity of pyloroplasty for the gastric tube through the posterior mediastinum in esophageal surgery, gastric emptying and duodenogastric reflux (DGR) were evaluated in 16 cases undergoing an anterior pylorectomy (group P) and in 16 cases treated by the finger bougie method (group F). First, the obstruction and reflux symptoms were examined based on a patient questionnaire using a brief scoring system. The median value of the symptom score showed the patients in P to have more symptoms than those in F; however, the difference was not significant (8.0 vs 6.0). Secondly, the swallowed Tc O₄ ⁻ (85 MBq) was counted using a gamma camera at three sites on the sternal bone in the upright position based on a gastric transit scintigram. Both the descending time of the RI peak and the clearance rates were similar between the two groups. Thirdly, intragastric 24-h pH monitoring was carried out. Antimony pH sensors were anchored 5 and 15 cm below the esophagogastrostomy. We could not find any difference between the two groups in both the % time pH>4 and %time pH>7. These findings thus revealed no big difference between groups P and F. The finger bougie method to drain the vagotomized posterior mediastinal stomach was found to achieve results similar to conventional pyloroplasty, while it was also simpler and safer.     

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.