Financial incentives for infection prevention and antimicrobial stewardship to reduce antibiotic use: Japan's nationwide observational study.

BACKGROUND: The Japanese government introduced financial incentives to reduce nationwide antibiotic use in hospital settings. AIM: This study aimed to determine whether the nationwide financial incentives for creating infection prevention and control (IPC) teams introduced in 2012 and antimicrobial stewardship (ASP) teams introduced in 2018 were associated with changes in antibiotic use and health resource utilization at a national level. METHODS: We conducted time-series analyses and a difference-in-differences study consisting of 3,057,517 inpatients with infectious diseases from 472 medical facilities during fiscal years 2011-2018 using a nationally representative inpatient database in Japan. The primary outcome was the days of therapy (DOT) of antibiotic use per 100 patient-days (PDs). The secondary outcomes consisted of types of antibiotic used, health resource utilization, and mortality. RESULTS: A total of 5,201,304 financial incentives were observed during 2012-2018, which resulted in a total of 12.1 billion JPY (≈110 million USD). Time-series analyses found decreasing trends in total antibiotic use (79.3-72.5 DOTs/100 PDs (8.6% reduction)) and carbapenem use (9.0-7.0 DOTs/100 PDs (7.8% reduction)) from 2011 to 2018 without adversely affecting other healthcare outcomes (e.g., mortality). In the difference-in-differences analyses, we did not observe meaningful changes in total antibiotic use between the incentivized and unincentivized hospitals for ASP teams, except for the northern part of Japan. No dose-response relationships were observed between the amount of financial incentives and reductions in antibiotic use during 2011-2019. CONCLUSIONS: Further research and efforts are needed to accelerate antimicrobial stewardship in hospital settings in Japan.

Molecular and catalytic properties of an arginine kinase from the nematode Ascaris suum.

We amplified the cDNA coding for arginine kinase (AK) from the parasitic nematode Ascaris suum, cloned it in pMAL plasmid and expressed the enzyme as a fusion protein with the maltose-binding protein. The whole cDNA was 1260 bp, encoding 400 amino acids, and the recombinant protein had a molecular mass of 45,341 Da. Ascaris suum recombinant AK showed significant activity and strong affinity ( K(m)(Arg) = 0.126 mM) for the substrate L-arginine. It also exhibited high catalytic efficiency ( k(ca)/K(m)(Arg) = 352) comparable with AKs from other organisms. Sequence analysis revealed high amino acid sequence identity between A. suum AK and other nematode AKs, all of which cluster in a phylogenetic tree. However, comparison of gene structures showed that A. suum AK gene intron/exon organization is quite distinct from that of other nematode AKs. Phosphagen kinases (PKs) from certain parasites have been shown to be potential novel drug targets or tools for detection of infection. The characterization of A. suum AK will be useful in the development of strategies for control not only of A. suum but also of related species infecting humans.

Postoperative evaluation of changes in extracranial-intracranial bypass graft using superficial temporal artery duplex ultrasonography.

BACKGROUND AND PURPOSE: Extracranial-intracranial (ECIC) bypass grafts have been assessed postoperatively by various neuroradiologic techniques. The aim of this prospective study was to evaluate postoperative changes in ECIC bypass graft by using superficial temporal artery duplex ultrasonography (STDU). Furthermore, this study assessed the ability of STDU to predict cerebrovascular reserve capacity (CVR). MATERIALS AND METHODS: Forty-five consecutive patients who underwent ECIC bypass procedure for atherosclerotic internal carotid artery occlusion were enrolled in this prospective study. All patients underwent single-photon emission CT and STDU preoperatively, 14 days after, 3 months after, 1 year after, and 2 years after ECIC bypass. RESULTS: The diameter and flow velocities of the ipsilateral superficial temporal artery (STA), and regional cerebral blood flow (rCBF) showed increase during the first 2 weeks and then remained stable, whereas CVR showed a constant improvement up to 2 years after surgery. The STA diameter and mean STA flow velocity correlated significantly with CVR at 1 year after surgery (r2 = 0.1232 and r2 = 0.08716, respectively; P < .05). A cutoff value of 1.8 mm STA diameter was determined as the most reliable value to predict CVR greater than 10% at 1 year after surgery. The positive predictive value was calculated as 96.6%, the negative predictive value as 43.8%, the sensitivity as 75.7%, the specificity as 87.5%, and the likelihood ratio as 6.056. CONCLUSIONS: ECIC bypass grafts can be assessed postoperatively in a noninvasive fashion with STDU. This technique provides information regarding patency as well as quantitative assessment of bypass function. Moreover, STDU is useful to predict CVR improvement.

Unique evolution of Bivalvia arginine kinases.

The clams Pseudocardium, Solen, Corbicula and Ensis possess a unique form of arginine kinase (AK) with a molecular mass of 80 kDa and an unusual two-domain structure, a result of gene duplication and subsequent fusion. These AKs also lack two functionally important amino acid residues, Asp(62) and Arg(193), which are strictly conserved in other 40-kDa AKs and are assumed to be key residues for stabilizing the substrate-bound structure. However, these AKs show higher enzyme activity. The cDNA-derived amino acid sequences of 40-kDa AKs from the blood clam Scapharca broughtonii and the oyster Crassostrea gigas were determined. While Asp(62) and Arg(193) are conserved in Scapharca AK, these two key residues are replaced by Asn and Lys, respectively, in Crassostrea AK. The native enzyme from Crassostrea and both of the recombinant enzymes show an enzyme activity similar to that of two-domain clam AKs and at least twofold higher than that of other molluskan AKs. Although the replacement of Asp(62) or Arg(193) by Gly in normal AK causes a considerable decrease in V(max) (6-15% of wild-type enzyme) and a two- to threefold increase in K(m) for arginine, the same replacement in Scapharca AK had no pronounced effect on enzyme activity. Together with the observation that bivalve AKs are phylogenetically distinct from other molluskan AKs, these results suggest that bivalve AKs have undergone a unique molecular evolution; the characteristic stabilizing function of residues 62 and 193 has been lost and, consequently, the enzyme shows higher activity than normal.

Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis.

BACKGROUND: Although enteral nutrition (EN) therapy for Crohn's disease has been confirmed to be as effective as steroid therapy, the precise mechanism responsible for the effects of EN remains unclear, although some of the therapeutic effects of EN are believed to be due to a low dietary fat content. In order to elucidate the influence of fat in EN, it is important to investigate not only the quantity of fat, but also the source of the fat. METHODS: We compared two enteral nutritional formulae: Elental (Ajinomoto) (elemental diet; ED), which contains only 1.5% fat, provided as long-chain triglycerides (LCT), versus Twinline (Snow Brand Milk Products) (TL), which contains a high percentage of fat (20.4%), provided mainly as medium-chain triglycerides (MCT). These formulae were tested on rat enteritis and rat colitis induced by trinitrobenzene sulfonic acid (TNBS). RESULTS: Both ED and TL reduced the manifestations of enteritis. TL had a stronger anti-inflammatory effect than ED for colitis. TL also had nutritional advantages as compared with ED, as shown by the total serum protein in the TL group being significantly higher than that in the ED group. CONCLUSION: The results indicate that intraluminal MCT is suitable as a fat energy source during intestinal inflammation in rats. We suggest that Twinline may be more useful to improve nutritional status and to reduce the mucosal inflammation in rat colitis, but that Twinline is equal in effect to Elental for rat enteritis.

Endovascular treatment of basilar artery trunk aneurysms with Guglielmi detachable coils: clinical experience with 41 aneurysms in 39 patients.

OBJECT: The authors present a retrospective analysis of their clinical experience in the endovascular treatment of basilar artery (BA) trunk aneurysms with Guglielmi detachable coils (GDCs). METHODS: Between April 1990 and June 1999,41 BA trunk aneurysms were treated in 39 patients by inserting GDCs. Twenty-seven patients presented with subarachnoid hemorrhage, six had intracranial mass effect, and in six patients the aneurysms were found incidentally. Eighteen lesions were BA trunk aneurysms, 13 were BA-superior cerebellar artery aneurysms, four were BA-anterior inferior cerebellar artery aneurysms, and six were vertebrobasilar junction aneurysms. Thirty-five patients (89.7%) had excellent or good clinical outcomes; procedural morbidity and mortality rates were 2.6% each. Thirty-six aneurysms were selectively occluded while preserving the parent artery, and in five cases the parent artery was occluded along with the aneurysm. Immediate angiographic studies revealed complete or nearly complete occlusion in 35 aneurysms (85.4%). Follow-up angiograms were obtained in 29 patients with 31 aneurysms: the mean follow-up period was 17 months. No recanalization was observed in the eight completely occluded aneurysms. In 19 lesions with small neck remnants, seven (36.8%) had further thrombosis, three (15.8%) remained anatomically unchanged, and nine (47.3%) had recanalization caused by coil compaction. In one patient (2.6%) the aneurysm rebled 8 years after the initial embolization. CONCLUSIONS: In this clinical series the authors show that the GDC placement procedure is valuable in the therapeutic management of BA trunk aneurysms. The endovascular catheterization of these lesions tends to be relatively simple, in contrast with more complex neurosurgical approaches. Endosaccular obliteration of these aneurysms also decreases the possibility of unwanted occlusion of perforating arteries to the brainstem.

Cutaneous necrosis after superficial temporal artery-to-middle cerebral artery anastomosis: is it predictable or avoidable?

OBJECTIVE: This study was carried out to determine whether a relationship exists between cutaneous necrosis after superficial temporal artery-to-middle cerebral artery anastomosis and background risk factors or surgical methods, and to determine whether such necrosis is predictable or avoidable. METHODS: Forty-seven patients (a total of 51 sides) with atherosclerotic lesions of the internal carotid artery or middle cerebral artery who underwent superficial temporal artery-to-middle cerebral artery anastomosis at the National Kyushu Medical Center Hospital between September 1, 1994, and August 31, 1999, were reviewed. Each procedure was analyzed to determine whether cutaneous necrosis was present postoperatively around the donor site, whether preexisting risk factors (hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, and arteriosclerosis obliterans) were present, and whether a flap or cutdown method or a single or double anastomosis was performed. RESULTS: Postoperative necrosis was clearly related to arteriosclerosis obliterans (P < 0.003). The tendency for a relationship between necrosis and smoking was noted. Although statistical analysis failed to demonstrate a significant difference, necrosis was found with the flap method but not with the cutdown method. CONCLUSION: Further study is needed using greater numbers to clarify the relationship between the surgical method and the presence of necrosis. To prevent cutaneous necrosis, however, it may be preferable to use the cutdown method in patients with the preexisting risk factors of arteriosclerosis obliterans or in smokers.

Hearing restoration from deafness after resection of a large cerebellopontine angle meningioma--case report.

A 61-year-old man presented with a large cerebellopontine angle meningioma manifesting as a 1-year history of deafness on the right side, in whom hearing was restored from the deaf state immediately after tumor resection. Neuroimaging demonstrated a large mass in the right cerebellopontine angle, originating at the region adjacent to the jugular foramen. Audiometry showed his hearing was off-scale (> 105 dB) on the right. The tumor was successfully removed through the retrosigmoid approach, and the integrity of the 7th and 8th cranial nerves was maintained. The patient regained hearing on the day after the operation, which continued to improve until near-normal. The 8th cranial nerve function may recover dramatically after removal of non-acoustic tumors, even if preoperative hearing loss is profound. To maximize the opportunity to regain hearing, approaches which devastate cochlear function should be avoided and more meticulous manipulation during tumor removal is needed.

Hepatic resection for liver metastasis of sigmoid colon cancer after incomplete percutaneous microwave coagulation therapy.

We report a case of colon cancer with liver metastasis that had been treated previously by sigmoidectomy and partial hepatic segmentectomy. A 55-year-old woman presented with two asynchronous liver metastases, which were treated with percutaneous microwave coagulation therapy. However, evaluation by dynamic computed tomography one week later showed incomplete necrosis in at least one tumor. Surgical resection was subsequently performed and histopathological examination showed the presence of viable cancer cells in both tumors. We conclude that surgical resection is perhaps the best curative method of treatment of metastatic liver tumors of colorectal carcinomas and that dynamic computed tomography is not always accurate for evaluating the effect of microwave coagulation therapy.

Acute intrathoracic incarceration of the stomach after laparoscopic Nissen fundoplication.

A rare case of paraesophageal hernia with complete intrathoracic incarceration of the stomach after laparoscopic Nissen fundoplication is described. An 85-year-old woman who had undergone laparoscopic Nissen fundoplication for gastroesophageal reflux disease presented 14 months later with nausea and vomiting. Esophagogastroendoscopy showed obstruction of the esophagogastric junction and gastric mucosal necrosis. Emergency laparotomy showed the stomach to be entirely strangulated into the thorax, with areas of necrosis. Gastrotomy was followed by resection of the necrotic anterior wall of the stomach, closure of the hiatus, and suturing of the stomach to the diaphragm. Appropriate closure of crura and anchoring suture between the stomach and diaphragm are helpful to prevent recurrent hernia after laparoscopic Nissen fundoplication.

Efficacy of oral adsorbent for treatment of peristomal fistula associated with Crohn's disease.

Perianal fistulae are frequently seen complications in Crohn's disease. Although surgical procedures such as Seton's method have been devised, many patients still suffer from fistulae that are resistant to conventional therapy. We administered oral adsorbent to a patient with disease Crohn's who had a complicated peristomal fistula that did not improve with conventional therapy. Six grams of oral adsorbent (AST-120) were added daily to a regimen of elemental diet therapy and prednisolone. The fistula gradually decreased in size after the administration of the oral adsorbent, and had healed completely after 40 days' treatment. There were no side effects from the oral adsorbent. This case report suggests that oral adsorbent is an effective treatment for peristomal fistula associated with Crohn's disease.

[Infratemporal fossa approach for mid-skull base lesion: its usefulness, surgical anatomy, and intraoperative device].

The usefulness of the infratemporal fossa type C approach is reported through a presentation of a case of clival chordoma, which was successfully treated by this approach. Although it is complicated and includes some demerits, this approach gives a shorter and wider access to mid-skull base pathology than other approaches. Among the demerits, deformity of the temporal region caused by extensive drilling of the bone could be minimized by cosmetic mastoidectomy, which was first applied during this approach by the authors. The surgical anatomy for this approach is demonstrated using a cadaver specimen.

Surgical correction of cryptotia with superiorly based superficial mastoid fascia and skin paddle.

An approach for the correction of cryptotia using a superiorly based superficial mastoid fascial flap and a skin paddle is introduced. The buried portion of the auricle was exposed through an incision made along the upper part of the helix, followed by an appropriate correction of the deformed cartilage. Protrusion of the upper portion of the auricle was accomplished using anchoring sutures. A small skin paddle was elevated from the caudal portion of the auricular sulcus with the superiorly based superficial mastoid fascia as the nutrient pedicle and transferred to the temporal skin defect. The procedure was performed in eight auricles in a total of seven patients with cryptotia. A satisfactory contour and protrusion of the auricle were maintained postoperatively, leaving the scar within the auricular sulcus.

Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease.

Elemental diet (ED) therapy has been established as primary therapy for Crohn's disease, and home enteral nutrition (HEN) has been reported to control relapse at a dose of more than 30kcal/kg of ideal body weight. However, a decrease in ED compliance with long-term use is becoming problem. We developed an n-3 fatty acid-rich diet and carried out nutritional education specifically for Crohn's disease patients using HEN to facilitate compliance and to improve their nutritional status. After the introduction of this n-3 rich diet, disease activity was not altered, and nutritional status, especially serum n-3 fatty acid levels, improved. The remission periods in patients with poor compliance seemed to be prolonged by the nutritional education. Thus, a n-3 rich diet in combination with nutritional education specific for Crohn's disease patients is very important for the in maintenance of high compliance and for maintaining nutritional balance.

Diagnosis and endovascular treatment of vertebral arteriovenous fistulas in neurofibromatosis type 1.

SUMMARY: We present diagnostic problems, strategies, techniques and material selection for endovascular treatment of high flow arteriovenous fistula (AVF) of tortuous and fragile vertebral artery (VA) with neurofibromatosis type 1 (NF1). Diagnosis of NF1 was easy in four of our cases because of neurofibromatosis, skin pigmentation and various skeletal abnormalities. These stigmas of NF1 were lacking in one case, and the only clue to the diagnosis was ovoid bone defects of the skull vault. Diagnosis was made by performing biopsy of scalp neurofibromas incidentally found on CT. In two initial cases, venous varix were packed with coils by transvenous approach after the transarterial embolisation failed to completely cure the fistula. In three recent cases, blood flow through the fistula was markedly reduced as an initial step by placing detachable coils into the distal and proximal stumps of the afferent VA. Then a liquid adhesive was injected under systemic hypotension to completely occlude the fistula. Control angiography revealed that the AVFs were completely occluded in all cases. Longterm angiographical and clinical status have been stable in all cases. Trying to attain complete occlusion of fistulas using detachable balloons is not an appropriate treatment option for high flow fistulas situated on markedly dilated, tortuous and fragile VAs of patients with NF1. Also, trapping of fistulas is not justified because of the numerous potential feeding pedicles, and makes the following procedure difficult.

[A case of cervical myelopathy due to dural arteriovenous fistula at the craniocervical junction].

A 70-year-old woman noted paresthesia ascending from both legs to her thighs 27 months previously. She also suffered from urinary urgency and incontinence. Thereafter, weakness in both legs developed and gradually became worse. At the time of admission, a neurological examination revealed diffuse atrophy and mild spasticity in all four extremities, bilateral mild weakness in both upper extremities, and severe weakness in both lower extremities. Her superficial sensation was moderately impaired below the Th 3 level on her right side, and below the Th 4 level on her left side along with a mildly decreased sense of vibration in her left leg. Marked hyperreflexia in all four extremities and bilateral pathological reflexes were also observed. Pollakisurea, urinary incontinence and constipation were also present. Cervical MRI showed a swelling of the spinal cord at the C3 to C7 levels. Inside the spinal cord, low signal intensity lesions were seen on the T1-weighted MRI, and high signal intensity lesions were observed on the T2-weighted MRI, and the rim of the cervical cord was also enhanced by gadolinium-DTPA. MR angiography revealed enlarged and tortuous vessels at the craniocervical junction, thus suggesting the presence of a dural arteriovenous fistula (AVF). Vertebral arteriography demonstrated abnormal vessels at the spinomedullary junction supplied by the right vertebral artery, which drained into the anterior and posterior spinal veins. After surgically treating the dural AVF, the swelling of the spinal cord, the abnormal signals on MRI, and the clinical symptoms all markedly improved. Although most of the spinal dural AVF were located at the thoracic and lumbar levels, the present case was considered to be a very rare case of dural AVF, since it was located at the craniocervical junction and thus led to the development of cervical myelopathy.