The effects of antifungal stewardship programs at a tertiary-care teaching hospital in Japan

Patients with invasive fungal diseases (IFDs) generally have a high mortality rate, and resistance to antifungal drugs and the high costs associated with it have led to recent problems, necessitating the appropriate use of antifungals. To this end, we launched Antifungal Stewardship Programs (AFSPs) in our hospital. Patients who were systemically administered antifungals from January 2011 to December 2016 were enrolled this study and divided into pre-intervention and intervention groups. No significant difference was observed in defined daily doses per 1000 patient-days (23.3 ± 8.0 vs 20.4 ± 10.8, p = 0.251) between the groups. The monthly average for the days of therapy per 1000 patient-days was significantly lower in the intervention group (15.1 ± 3.1 vs 12.7 ± 4.3, p = 0.009). The cost of the antifungals reduced over the 3-year period by $260,520 (13.5%). Furthermore, a decreasing trend was observed in both the 30-day mortality (40.9% vs 30.0%, p = 0.414) and in-hospital mortality (63.6% vs 36.7%, p = 0.054) in patients with candidemia. Our results indicate that AFSPs are efficacious and cost-effective approaches.     

Optimal entry position on the lateral femoral surface for outside-in drilling technique to restore the anatomical footprint of anterior cruciate ligament

Purpose

To investigate the optimal starting points for drilling on the lateral femoral condyle for better coverage of the anatomical footprint of the anterior cruciate ligament (ACL) using the outside-in (OI) technique in a single-bundle ACL reconstruction.

Methods

Femoral tunnel drilling was simulated on three-dimensional bone models from 40 subjects by connecting the centre of the ACL footprint with various points on the lateral femoral surface. The percentage of the femoral footprint covered by apertures of the virtual tunnel sockets with 9 mm diameter was calculated for each tunnel.

Results

The mean percentages of the femoral footprint covered by the apertures of the virtual tunnel sockets were significantly higher when drilled at 2 and 3 cm from the lateral epicondyle on a 45° line and a 60° line anterior from the proximal–distal axis than the other points. However, articular cartilage damage was occurred in nine subjects at 3 cm on a 60° line and eight subjects at 3 cm on a 45° line. Posterior wall blowout occurred in five subjects at 3 cm on a 45° line. Thus, OI drilling at 3 cm from the epicondyle has a risk of these complications.

Conclusion

During the OI drilling of the femoral tunnel, connecting the centre of the anatomical footprint of the ACL and the entry drilling point at 2 cm from the lateral epicondyle on between the 45° line and the 60° line anterior from the proximal–distal axis provides an oval-shaped socket aperture that covers and restores the native ACL footprint as nearly as possible.

Level of evidence

III.

     

State-dependent blocking actions of azimilide dihydrochlo-ride (NE-10064) on human cardiac Na(+) channels.

BACKGROUND: Azimilide reportedly blocks Na(+) channels, although its mechanism remains unclear. METHODS AND RESULTS: The kinetic properties of the azimilide block of the wild-type human Na(+) channels (WT: hH1) and mutant DeltaKPQ Na(+) channels (DeltaKPQ) expressed in COS7 cells were investigated using the whole-cell patch clamp technique and a Markovian state model. Azimilide induced tonic block of WT currents by shifting the h infinity curve in the hyperpolarizing direction and caused phasic block of WT currents with intermediate recovery time constant. The peak and steady-state DeltaKPQ currents were blocked by azimilide, although with only a slight shift in the h infinity curve. The phasic block of peak and steady-state DeltaKPQ currents by azimilide was significantly larger than the blocking of the peak WT current. The affinity of azimilide predicted by a Markovian state model was higher for both the activated state (Kd(A) =1.4 micromol/L), and the inactivated state (Kd(I) =1.4 micromol/L), of WT Na(+) channels than that for the resting state (Kd(R) =102.6 micromol/L). CONCLUSIONS: These experimental and simulation studies suggest that azimilide blocks the human cardiac Na(+) channel in both the activated and inactivated states.     

Clinical evaluation of double stenting for duodenal and biliary obstructions caused by pancreatic head carcinoma using covered self‐expandable metallic stents

Five patients with non‐resectable pancreatic head carcinoma complicated by duodenal and biliary obstructions were successfully treated by double stenting with covered self‐expandable metallic stents (EMS). Diamond (Boston Scientific, Natick City, MA, USA) stents covered with a polyurethane membrane were used to treat biliary obstructions, whereas covered Ultraflex (Boston Scientific) stents for esophageal stenting were used to treat duodenal obstructions. That is, Diamond stents were initially placed in the biliary tract percutaneously in one patient and endoscopically in the remaining four patients. Subsequently, covered Ultraflex stents were placed in the duodenum. Double stenting with EMS was successfully performed in all five patients without inducing early technical complications. All patients were able to take a liquid diet orally at a mean 1.6 days after the double stenting procedure and were able to eat solid foods thereafter. Sludge‐induced biliary obstructions were detected in two patients 3 and 6 months after the placement of EMS. However, recurrent biliary obstruction was not noted in the remaining three patients. The EMS left in the duodenum were not obstructed during the observation period. The survival period of the patients ranged from 86 to 363 days (mean 172 days). There have not been any reports evaluating the usefulness of double stenting using covered EMS for duodenal and biliary obstructions. Because favorable results were obtained by double stenting in our patients, stenting for duodenal and biliary obstructions caused by non‐resectable pancreatic head carcinoma may become a useful treatment modality substituting for bypass surgery.     

Comparison of ulinastatin, gabexate mesilate, and nafamostat mesilate in preservation solution for islet isolation

For islet transplantation, maintaining organ viability after pancreas procurement is critically important for optimal graft function and survival. We recently reported that islet yield was significantly higher in the modified ET-Kyoto (MK) solution, which includes a trypsin inhibitor (ulinastatin), compared with the UW solution, and that the advantages of MK solution are trypsin inhibition and less collagenase inhibition. In this study, we compared ulinastatin with other trypsin inhibitors, gabexate mesilate, and nafamostat mesilate, in preservation solution for islet isolation. Ulinastatin was easily dissolved in ET-Kyoto solution, while ET-Kyoto with gabexate mesilate and nafamostat mesilate became cloudy immediately after addition. Although there were no significant differences in islet yield among the three groups, viability was significantly higher for the MK group than for the GK group or the NK group. The stimulation index was significantly higher for the MK group than for the GK group. In summary, there are no other trypsin inhibitors that are more effective than ulinastatin. Based on these data, we now use ET-Kyoto solution with ulinastatin for clinical islet transplantation.     

Improvement of porcine islet isolation by inhibition of trypsin activity during pancreas preservation and digestion using α1-antitrypsin

Porcine islets are considered to be a promising resource for xenotransplantation. However, it is difficult to isolate porcine islets because of the marked fragility and rapid dissociation. Endogenous trypsin is one of the main factors to damage islets during the isolation procedure. Recent studies have suggested that trypsin inhibitors during the preservation of pancreas or the collagenase digestion can improve the result of islet isolation. In this study, we examined whether α1-antitrypsin (Aralast?), which inhibits several endogenous proteases and has immunomodulatory properties, can protect islets from the proteases and improve the results of porcine islet isolation. Twelve porcine pancreata were divided into three groups: without Aralast group (standard, n = 5), preserved with Aralast using the ductal injection (DI) method (DI, n = 3), and with Aralast using the DI method and in the collagenase solution (DI+C, n = 4). Efficacy of islet isolation was assessed by islet yields, purity, and viability. The trypsin activity of the preservation and the digestion solution during the isolation procedure was measured. During islet isolation, the trypsin activity in DI+C group was significantly inhibited compared to the standard group, whereas DI group showed less effect than DI+C group. The average of postpurification islet equivalents (IEQ) per pancreas weight in the DI+C group was significantly higher than the standard group (standard: 3516 ± 497 IEQ/g, DI: 4607 ± 1090 IEQ/g, DI+C: 7097 ± 995 IEQ/g; p = 0.017 between standard and DI+C). In the DI+C group, stimulation index was higher than in other groups, although there was no significant difference. The presence of Aralast in both DI solution and collagenase solution markedly inhibited trypsin activity during pancreas digestion procedure and improved the porcine islet isolation. Inhibition of trypsin activity by Aralast could improve porcine islet isolation.     

A Case of Purulent Pancreatic Ductitis Successfully Treated by Endoscopic Stenting

A 50‐year‐old male received conservative medical treatment for acute exacerbation of chronic pancreatitis. High fever, abdominal pain, as well as enhancement of inflammatory response and pancreatic enzymes in serum, persisted after treatment for 1 month. Purulent pancreatic fluid was drained by endoscopically placing an 8F plastic stent in the main pancreatic duct, resulting in marked improvement of clinical symptoms. This case appears to provide useful information in considering indications for pancreatic stents.