Prospective, randomized, cross-over pilot study of the effects of Rikkunshito, a Japanese traditional herbal medicine, on anorexia and plasma-acylated ghrelin levels in lung cancer patients undergoing cisplatin-based chemotherapy.

Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748.

Muraminomicins, novel ester derivatives: in vitro and in vivo antistaphylococcal activity.

Novel muraminomicin derivatives with antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) were synthesized by esterification of the hydroxy group on the diazepanone ring of muraminomicin Z1. Compound 1b (DS14450354) possessed a diheptoxybenzyl-ß-Alanyl-ß-Alanyl group and exhibited minimum inhibitory concentrations (MICs) against MRSA comparable to those against methicillin-susceptible S. aureus (MSSA). The MICs that inhibited 50 and 90% of the strains were 1 and 2 µg/mL, respectively. Compound 1a (DS60182922) possessed an aminoethylbenzoyldodecylglycyl moiety and showed bactericidal activity against MSSA Smith. The bactericidal activity of 1a against MRSA 10925 was comparatively lower, whilst 1b exhibited dose-dependent bactericidal activity against MRSA 10925. The mutation frequency of 1b was lower than that of 1a. An amino acid substitution (F226I) was observed in MraY mutants isolated from culture plates containing 1a or 1b. Subcutaneous 1a and 1b administration showed good therapeutic efficacy in murine systemic infection models with MSSA Smith and MRSA 10925, comparable to that of vancomycin, suggesting that the novel muraminomicin derivatives may be effective therapeutic agents against MRSA that warrant further investigation. A scheme for the formulation of the key ester intermediate, requiring no HPLC preparation, was also established.

Therapeutic Strategy for Incarcerated Obturator Hernia Using Preoperative Manual Reduction and Laparoscopic Repair.

BACKGROUND: Obturator hernia (OH) is a rare but serious disease associated with high morbidity and mortality due to advanced patient age and comorbidities. This study evaluated the feasibility of a laparoscopic approach to OH. STUDY DESIGN: We retrospectively reviewed the records of 32 patients (median age 84 years; 31 women) with OH treated between 2003 and 2016. RESULTS: Five patients with incidental OH underwent total extraperitoneal (TEP) repair. Of 27 patients with incarcerated OH, 18 patients underwent laparotomy, 13 of which required bowel resection, and the remaining 9 patients underwent preoperative ultrasound-guided manual OH reduction. Of 6 patients with successful OH release, 3 and 2 patients underwent TEP and transabdominal preperitoneal repair, respectively, and 1 patient declined the operation. Three patients with failure underwent laparoscopic exploration and conversion to open operation for bowel resection. Comparing the open and laparoscopic groups, the median operation times were 67.5 minutes vs 124 minutes, respectively (p = 0.004); median postoperative stay was 19 vs 11 days, respectively (p = 0.028); and Clavien-Dindo grade II or higher complications tended to be lower (28% vs 8%, respectively; p = 0.359). Even in patients without bowel resection, the median postoperative stay was significantly shorter in the laparoscopic group compared with the open group (7.5 vs 15 days, respectively; p = 0.032). During a mean follow-up of 24.5 months, the 3-year recurrence rate for OH was 25% for non-mesh repair and 0% for mesh repair (p = 0.335). Three- and 5-year cumulative survival rates were 83% and 71%, respectively. CONCLUSIONS: Laparoscopic operations after ultrasound-guided manual reduction can be an alternative to emergent laparotomy in select OH patients.

Comparison of transurethral enucleation with bipolar and transurethral resection in saline for managing benign prostatic hyperplasia.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Transurethral enucleation with bipolar (TUEB) has been widely adopted as an alternative to standard TURP, although the surgical technique, efficacy and safety of TUEB have not been described so far. The present study provides illustrations of the TUEB technique, as well as peri-operative, 6-month and 12-month follow-up results of TUEB from a retrospective review of a single-institution experience comparing the efficacy and safety of TUEB and transurethral resection in saline for managing BPH. OBJECTIVE: • To illustrate the transurethral enucleation with bipolar (TUEB) technique and compare the efficacy and safety of TUEB and transurethral resection in saline (TURis) for managing benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: • A retrospective review of a single-institution experience of 110 consecutive TUEB or TURis between 2008 and 2011 at our hospital was performed aiming to compare the efficacy and safety of TUEB and TURis for managing BPH (55 patients in each group). • Peri-operative data included operating time, resected tissue weight, changes in haemoglobin, duration of catheterization, hospital stay and early complications. • Postoperative outcomes included 6- and 12-month postoperative International Prostate Symptom Score (IPSS), and Quality of Life (QoL) score, uroflowmetry findings, change in serum prostate-specific antigen level and all late complications in the two groups. RESULTS: • Both groups were well matched for age, preoperative prostate volume, IPSS, QoL and uroflowmetry findings. • The change in haemoglobin at postoperative day 1 in the TUEB group was significantly less than in the TURis group (1.08 vs 1.60 g/dL; P < 0.001). • Catheterization time and hospital stay were significantly shorter in the TUEB group than in the TURis group and the mean retrieved tissue weight in the TUEB group was larger than that in the TURis group (41.3 vs 31.7 g; P = 0.007). • Patients in the two arms had comparable improvements in postoperative IPSS, QoL, maximum flow rate and postvoid residual urine volume. • The rates of complications were equally low with each procedure. CONCLUSION: • TUEB is superior to TURis, with less bleeding, as well as decreased catheter time and hospital stay, although showing equivalent efficacy at 12 months of follow-up.

Synthesis and anti-influenza evaluation of polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives.

Polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives on a poly-L-glutamine backbone are described. Aiming for a longer retention time of 4-guanidino-Neu5Ac2en (zanamivir) in bronchi and lungs, we focused on supermolecules bearing 4-guanidino-Neu5Ac2en derivatives bound at their C-7 position through noncleavable alkyl ether linkages. We first found that alkylation of the 7-hydroxyl group of sialic acid derivative 8 proceeded smoothly, and produced 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives 13, which exhibited equipotent inhibitory activity against not only influenza A virus sialidase but also influenza A virus in the cell culture. Next, we synthesized poly-L-glutamine bearing 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives linked by amide bonds, 26, which showed enhanced antiviral activity against influenza A virus and more potent efficacy in vivo relative to a monomeric sialidase inhibitor.

Synthesis and anti-influenza evaluation of orally active bicyclic ether derivatives related to zanamivir.

We synthesized bicyclic ether sialidase inhibitors such as tetrahydro-furan-2-yl, tetrahydro-pyran-2-yl, and oxepan-2-yl derivatives related to zanamivir. These compounds substituted by diol at the C-3' and C-4' positions resulted in the retention of low nanomolar inhibitory activities against not only influenza A virus sialidase but also influenza A virus in cell culture. Compound 11a in particular showed comparable efficacy in vivo relative to that of oseltamivir phosphate.