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.     

AP-1 (c-Fos/c-Jun) is required for corneal epithelial spreading

PURPOSE: We previously demonstrated that the AP-1 components c-fos/c-jun are up-regulated in healing rat corneal epithelium in a relatively early phase following epithelial débridement, implicating the AP-1 function in the initiation of cell movement. To explore this hypothesis, we examined the effect of lack of c-Fos and c-Jun protein expressions on the spreading of corneal epithelium and in situ in organ culture. Antisense-oligonucleotide (AS) c-fos-null mice were used for this purpose. METHODS: A rectangular piece of corneal tissue (2 x2 mm) was obtained from each eye of recently killed adult C57BL/6 mice and was incubated for 11 h in culture medium with 8 microM c-fos AS or c-jun AS probe. Sense probes were used for negative control. A rectangular section of corneal tissue was also obtained from each eye of c-fos(-/-), c-fos(+/-) and c-fos(+/+) mice and was organ-cultured for 11 h. The length of the path of epithelial spreading on stromal cut surface (both sides) was measured in hematoxylin-eosin-stained specimens. Data were analyzed by unpaired Student's t-test. RESULTS: Addition of c-fos AS to the medium decreased the length of epithelial spread to 40.36% of that in the control with the S probe. Addition of c-jun AS decreased the length of epithelial spreading rate to 42.71% of control with S probe. Lacking c-Fos decreased the epithelial spreading to 17.73% of control data from c-fos(+/-) and c-fos(+/+) mice. CONCLUSION: AP-1 (c-Fos/c-Jun) is required for the corneal epithelial spreading.     

Serum amyloid A protein in acute viral infections

Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections.     

Surgical simulator for temporal bone dissection training

Temporal bone dissection plays an important role in the training of surgeons; however, they are difficult to obtain.AimTo develop a synthetic replica of the temporal bone for dissection training.Study DesignExperimental.Materials and MethodsAn acrylic synthetic resin replica was obtained from a human temporal bone. For the evaluation of the method, we selected five ear surgeons to dissect the model in a laboratory of experimental surgery. A questionnaire was filled, assessing external appearance, the simulation of procedures (placement of ventilation tube, mastoidectomy, decompression of the facial nerve and translabyrinthine access to the internal auditory canal) and their final conclusion.ResultsThe evaluation indicated satisfaction in using the model (80%), being more evident concerning the dissection of the mastoid segment of the facial nerve and translabyrinthine access to the internal auditory canal. The placement of a ventilation tube was reasonable for 60% and satisfactory for 40% of them. Mastoidectomy was satisfactory for 60% and fully satisfactory for 40%.ConclusionDissection in this simulator does not replace otologic training in cadaveric temporal bones. However, given the increasing difficulty in obtaining the latter, the development of new teaching tools should be encouraged to continuously improve surgeons.     

Intrathoracic infusion with a combination of low-dose minocycline, OK-432 and cisplatin for malignant pleural effusion

We investigated the effectiveness and complications of intrathoracic infusion with a combination of cisplatin, OK-432, and minocycline for malignant pleural effusion. All patients were hospitalized with chest tube drainage of pleural effusion until the daily drainage volume was less than 100 ml. Twenty-five mg of minocycline, 1 to 3 KE of OK-432, and 5 to 10 mg of cisplatin were instilled into the pleural space. The administration was repeated until drainage effusion disappeared. Therapeutic effect was evaluated according to the following criteria: (1) excellent, no fluid reaccumulation for at least 4 weeks as determined by chest radiogram and clinical evaluation; (2) effective, fluid reaccumulation less than 50% of original effusion with no need of thoracentesis for symptomatic relief within 4 weeks after treatment; and (3) failure, reaccumulation of more than 50% of the original effusion requiring thoracentesis to relieve symptoms within 4 weeks of treatment. Twelve patients with malignant effusion received the combination treatment; 11 patients had primary lung cancer and one had metastatic lung tumor from cancer of the rectum. In all cases, the histology or cytology revealed adenocarcinoma. Eleven of the 12 patients had an excellent response with relief of clinical symptoms. The remaining case failed to show any improvement. Complications such as local pain, fever, nausea, and vomiting were mild and transient. We conclude that combination administration of low-dose minocycline, OK-432, and cisplatin into the thoracic cavity for malignant effusion is an effective alternative treatment with the potential for improvement of the general condition and reduced morbidity.     

Extended right hepatectomy for hilar cholangiocarcinoma with resection of the left hepatic duct prior to hepatic resection

Extended hepatectomy for hilar cholangiocarcinoma results in high operative or in-hospital mortality rates despite of the recent progress in perioperative management. As a new procedure to prevent postoperative hepatic failure in hilar cholangiocarcinoma infiltrating predominantly the right hepatic duct, we devised a combination of extended right lobectomy plus caudal lobectomy with resection of the left hepatic duct prior to hepatic resection by utilizing intraoperative cholangiography, and applied the procedure to a 70-year-old patient. He had a favorable postoperative course and remains recurrence-free at 4 years after operation. This is a procedure for confining the extent of hepatectomy to the minimum necessary, aiming at curative resection of hilar cholangiocarcinoma.     

Development of magnifying video endoscopes with high resolution

Background: The diagnostic capability of a video‐endoscope has been remarkably enhanced by using a high pixel count charge‐coupled device (CCD) and is getting closer to that of the stereomicroscope as its image quality is improved. From this standpoint, the authors have been developing high‐resolution magnifying video‐endoscopes. Methods: There are two methods available to increase the resolution of a video‐endoscope: (i) use a CCD with large pixel number and (ii) optically magnify the image impinging on the CCD. Since the video‐endoscope using a 410 Kilo (K) pixel count CCD was introduced in 1993, the authors have been developing a video‐endoscope using a large pixel count number CCD in pursuit of obtaining better image quality and resolution. Also, the technological innovations in CCD manufacturing have allowed CCDs to become much smaller in size with higher pixel numbers. As the CCD size decreases, the distal part of a video‐endoscope can be made thinner. With respect to optical magnification, two methods are available, the fixed close‐focusing system and variable focus. Results: With combined use of the variable focus magnification and the electronic magnification, a magnification more than × 100 can be achieved on a 14″ television monitor with higher resolution power and wider depth of field. Conclusions: The images captured by the latest magnifying video‐endoscope prove that the image quality of video‐endoscopy is improving and is approaching the diagnostic capability of the stereomicroscope.