Comparison of the efficacy of three topical antiseptic solutions for the prevention of catheter colonization: a multicenter randomized controlled study.

BACKGROUND: To compare the efficacy of three antiseptic solutions [0.5%, and 1.0% alcohol/chlorhexidine gluconate (CHG), and 10% aqueous povidone-iodine (PVI)] for the prevention of intravascular catheter colonization, we conducted a randomized controlled trial in patients from 16 intensive care units in Japan. METHODS: Adult patients undergoing central venous or arterial catheter insertions were randomized to have one of three antiseptic solutions applied during catheter insertion and dressing changes. The primary endpoint was the incidence of catheter colonization, and the secondary endpoint was the incidence of catheter-related bloodstream infections (CRBSI). RESULTS: Of 1132 catheters randomized, 796 (70%) were included in the full analysis set. Catheter-tip colonization incidence was 3.7, 3.9, and 10.5 events per 1000 catheter-days in 0.5% CHG, 1% CHG, and PVI groups, respectively (p = 0.03). Pairwise comparisons of catheter colonization between groups showed a significantly higher catheter colonization risk in the PVI group (0.5% CHG vs. PVI: hazard ratio, HR 0.33 [95% confidence interval, CI 0.12-0.95], p = 0.04; 1.0% CHG vs. PVI: HR 0.35 [95% CI 0.13-0.93], p = 0.04). Sensitivity analyses including all patients by multiple imputations showed consistent quantitative conclusions (0.5% CHG vs. PVI: HR 0.34, p = 0.03; 1.0% CHG vs. PVI: HR 0.35, p = 0.04). No significant differences were observed in the incidence of CRBSI between groups. CONCLUSIONS: Both 0.5% and 1.0% alcohol CHG are superior to 10% aqueous PVI for the prevention of intravascular catheter colonization. TRIAL REGISTRATION: Japanese Primary Registries Network; No.: UMIN000008725 Registered on 1 September 2012.

Mast cell hyperactivity underpins the development of oxygen-induced retinopathy.

Mast cells are classically thought to play an important role in protection against helminth infections and in the induction of allergic diseases; however, recent studies indicate that these cells also contribute to neovascularization, which is critical for tissue remodeling, chronic inflammation, and carcinogenesis. Here, we demonstrate that mast cells are essential for sprouting angiogenesis in a murine model of oxygen-induced retinopathy (OIR). Although mouse strains lacking mast cells did not exhibit retinal neovascularization following hypoxia, these mice developed OIR following infusion of mast cells or after injection of mast cell tryptase (MCT). Relative hypoxia stimulated mast cell degranulation via transient receptor potential ankyrin 1. Subsequent surges in MCT stimulated retinal endothelial cells to produce monocyte chemotactic protein-1 (MCP1) and angiogenic factors, leading to sprouting angiogenesis. Mast cell stabilizers as well as specific tryptase and MCP1 inhibitors prevented the development of OIR in WT mice. Preterm infants with early retinopathy of prematurity had markedly higher plasma MCT levels than age-matched infants without disease, suggesting mast cells contribute to human disease. Together, these results suggest therapies that suppress mast cell activity should be further explored as a potential option for preventing eye diseases and subsequent blindness induced by neovascularization.

Low-dose immunoglobulin G is not associated with mortality in patients with sepsis and septic shock.

BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655-1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively). CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality. TRIAL REGISTRATION: University Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.

Clinical Serum Therapy: Benefits, Cautions, and Potential Applications.

Blood serum from immunized humans or animals (e.g., horses) contains relevant antibodies and has been used as serum therapy to treat many diseases or envenomation events. The effectiveness of blood serum was initially discovered in 1890 when Kitasato and von Behring observed the effectiveness of this type of therapy against diphtheria and tetanus. Serum therapies played an important role in the advancement of modern medicine prior to the development of penicillin and steroids. At present, several types of serum therapy remain in clinical use. However, some physicians have a limited understanding of the nature and the benefits of serum therapy and the factors that require particular attention. In this review, we set out to clarify the benefits, cautions, and potential applications of serum therapy in the context of conditions such as gas gangrene, diphtheria, botulism, and tetanus and bites from three snake species (mamushi, habu, and yamakagashi) and the redback spider. It is hoped that this review will help clinicians to learn about clinical serum therapies and become familiar with their applications.

Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study.

Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646-1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013.

Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively.

Early and frequent development of ocular hypertension in children with nephrotic syndrome.

BACKGROUND: Prednisolone, the first-line treatment for children with nephrotic syndrome, causes severe side effects. One of these side effects is ocular hypertension, which can result in severe and permanent visual disturbance. However, the exact prevalence, severity and timing of development of ocular hypertension have yet to be fully explored in this pediatric patient group. METHODS: In this retrospective cohort study, children with nephrotic syndrome treated with prednisolone for their first episode were analyzed. Intraocular pressure was screened with an iCare® tonometer and confirmed with Goldmann applanation tonometry before the initiation of prednisolone treatment and at 1 and 4 weeks thereafter. RESULTS: A total of 26 children with nephrotic syndrome were included in this study, of whom eight (30.8 %) required treatment with eye drops for ocular hypertension. The median time interval between the diagnosis of ocular hypertension and start of treatment was 9 (range 5-31) days. At relapse of nephrotic syndrome, all children who had undergone treatment for ocular hypertension in their first episode again required treatment for ocular hypertension. CONCLUSIONS: Routine ophthalmologic examination should be conducted from the early phase after the start of prednisolone treatment. In addition, children with episodes of ocular hypertension may be at greater risk of its reappearance with relapse of the nephrotic syndrome.

Factors associated with the clinical outcomes of paediatric out-of-hospital cardiac arrest in Japan.

OBJECTIVES: To better understand and predict clinical outcomes of paediatric out-of-hospital cardiac arrest (OHCA). DESIGN: A population-based, observational study. SETTING: The National Japan Utstein Registry. PARTICIPANTS: 2900 children aged 5-17 years who experienced OHCA and received resuscitation by emergency responders. Signal detection analysis using 17 variables was applied to identify factors associated with OHCA outcomes; the primary endpoint was cerebral performance category (CPC) 1 or 2. A validation study was conducted to verify the model. RESULTS: OHCA was identified as cardiac origin in 706 participants and non-cardiac origin in 2194 participants. Rates of CPC 1 or 2 for cardiac and non-cardiac causes were 20% and 6.4%, respectively. Cardiac origin arrest was categorised following signal detection into six subgroups defined by public automated external defibrillator use, defibrillation by emergency medical service, age, initial ECG rhythm and eye-witness to arrest; the ranges of CPC 1 or 2 in the six subgroups were between 87.5% and 0.7%. Non-cardiac origin arrest was categorised into four subgroups. Bystander rescue breathing was the most significant factor contributing to outcome; additionally, two other factors-eye-witness to arrest and age-were also significant. CPC 1 or 2 rates ranged between 38.5% and 4% across the four subgroups. Rates of CPC 1 or 2 in the validation study did not differ among any subgroup. CONCLUSIONS: For children who have OHCA from non-cardiac origin, bystander rescue breathing is mandatory to achieve CPC 1 or 2.

Clinical features of congenital retinal folds.

PURPOSE: To investigate the clinical features and prognosis of congenital retinal folds without systemic associations. DESIGN: Retrospective observational case series. METHODS: The characteristics, clinical course, ocular complications, and best-corrected visual acuity (BCVA) of eyes with congenital retinal folds were studied during the follow-up periods. The affected and fellow eyes were examined by slit-lamp biomicroscopy, binocular indirect ophthalmoscopy, and fundus fluorescein angiography. The parents and siblings of each patient also underwent ophthalmoscopic examinations. The BCVA was measured using a Landolt ring VA chart. RESULTS: One hundred forty-seven eyes of 121 patients with congenital retinal folds were examined. Fifty-five patients (45.5%) were female. The fold was unilateral in 95 patients (78.5%), and 69 of those patients (72.6%) had retinal abnormalities in the fellow eye. The meridional distribution of folds was temporal in 136 eyes (92.5%). The family history was positive in 32 patients (26.4%). Secondary fundus complications, including fibrovascular proliferation and tractional, rhegmatogenous, and exudative retinal detachments, developed in 44 eyes (29.9%). The BCVAs could be measured in 119 eyes and ranged from 20/100 to 20/20 in 5 eyes (4.2%), 2/100 to 20/200 in 45 eyes (37.8%), and 2/200 or worse in 69 eyes (58.0%). The follow-up periods ranged from 4 to 243 months (mean, 79.7 ± 58.9 months). CONCLUSIONS: These clinical features suggested that most congenital retinal folds may result from insufficient retinal vascular development, as in familial exudative vitreoretinopathy, rather than persistent fetal vasculature. Adequate management of active retinopathy and late-onset complications, especially retinal detachment, is required.

Perforating eyelid injury extending to the brain stem in a 17-year-old woman: a case report.

INTRODUCTION: This case report describes a patient who had a perforating eyelid injury that extended to the brain stem. CASE PRESENTATION: A 17-year-old Japanese woman complained of decreased vision in her right eye, with severe ocular pain and headaches, after the metal tip of an umbrella struck her upper right eyelid accidentally. Her vision in the right eye decreased to light perception with commotio retinae, intraretinal hemorrhage, and severe lid swelling. Magnetic resonance imaging (MRI) demonstrated edema of the head of the caudate nucleus and putamen, and the edema extended to the hypothalamus. The MRI findings indicated that the umbrella tip had penetrated through the eyelid and the posterior orbital wall. Vision improved to 20/50 in the right eye, with subretinal fibrosis caused by the choroidal rupture. CONCLUSIONS: We recommend that MRI be performed on the orbit and brain in patients who appear to have symptoms that are inconsistent with the observed injury and when a severe orbitocranial injury is suspected.

CrxOS maintains the self-renewal capacity of murine embryonic stem cells.

Embryonic stem (ES) cells maintain pluripotency by self-renewal. Several homeoproteins, including Oct3/4 and Nanog, are known to be key factors in maintaining the self-renewal capacity of ES cells. However, other genes required for the mechanisms underlying this process are still unclear. Here we report the identification by in silico analysis of a homeobox-containing gene, CrxOS, that is specifically expressed in murine ES cells and is essential for their self-renewal. ES cells mainly express the short isoform of endogenous CrxOS. Using a polyoma-based episomal expression system, we demonstrate that overexpression of the CrxOS short isoform is sufficient for maintaining the undifferentiated morphology of ES cells and stimulating their proliferation. Finally, using RNA interference, we show that CrxOS is essential for the self-renewal of ES cells, and provisionally identify foxD3 as a downstream target gene of CrxOS. To our knowledge, ours is the first delineation of the physiological role of CrxOS in ES cells.

Outcome of early surgery for bilateral congenital cataracts in eyes with microcornea.

PURPOSE: To report the outcome of early surgery for bilateral congenital cataracts in eyes with microcornea. DESIGN: Interventional case series. METHODS: We retrospectively reviewed 22 eyes of 11 patients with microcorneas who underwent early surgery for bilateral congenital cataracts. All patients underwent lensectomy and anterior vitrectomy via the limbal approach by 12 weeks of age. The corneal diameters at the time of surgery ranged from 7.0 to 9.0 mm. The mean age at the time of surgery was 7.7 +/- 3.3 weeks (range, two to 12 weeks); the follow-up period was 115 +/- 58 months (range, 40 to 199 months). Aphakic eyes were corrected with spectacles or contact lenses. Visual acuities and the postoperative complications were evaluated periodically. RESULTS: The morphologic types of cataract were nuclear (12 eyes), complete (eight eyes), and membranous (two eyes). Other preoperative ocular abnormalities included iris hypoplasia in 10 eyes and persistent fetal vasculature in three eyes. Systemic abnormalities were found in four patients. Postoperative complications occurred in 11 eyes (50%), including glaucoma (nine eyes), exudative retinal detachment (two eyes), rhegmatogenous retinal detachment, and secondary membrane formation, in one eye each. The binocular visual acuity was 20/40 to 20/20 in six patients (55%), 20/200 to 20/100 in two patients (18%), and 2/100 or worse in three patients (27%) who developed postoperative glaucoma. CONCLUSION: Despite microcorneas, favorable visual outcomes were achieved after early surgery in this series. However, adequate management of postoperative complications, especially glaucoma, is required.

Prognosis of patient with cardiopulmonary arrest transported to Kyushu University Hospital.

Three hundreds and sixty six patients with out-of-hospital cardiopulmonary arrest, transported to the Kyushu University Hospital from 2000 to 2006, were examined using the Utstein style in witnessed cardiogenic cardiopulmonary arrest patients. Also, we examined the influence on prognosis due to the difference in the treatment of airway control in out-of-hospital settings. Nineteen patients out of 78 witnessed cardiogenic out-of-hospital cardiopulmonary arrest patients were discharged alive and 11 were with a good prognosis. The number of cases where an initial electrocardiographic complex showed ventricular fibrillation or pulseless ventricular tachycardia was higher than formerly reported in Japan and was equal to the incidence reported in Europe and America. In addition, the survival discharge rate of patients with the ventricular fibrillation or pulseless ventricular tachycardia was higher than that previously reported in Japan and was similar to European and American results. Manual airway maintenance using a bag valve mask was more successful in terms of the survival discharge rate compared to the use of advanced airway devices. By the time course, collapse to cardiopulmonary resuscitation interval, collapse to initial defibrillation interval and collapse to the return of spontaneous circulation interval were shorter in the group discharged with a good prognosis, especially in the witnessed ventricular fibrillation or pulseless ventricular tachycardia patients corresponding to former reports. Most patients with a good prognosis resuscitated before arrival at the hospital. These results suggest the prehospital treatment is the critical point other than in-hospital treatment.

Geriatric patients presenting to the emergency department of a Japanese university hospital.

To evaluate the trend of elderly patients visiting the emergency department of a Japanese University Hospital, out patient-based records were reviewed of the emergency department of Kyushu University Hospital from 2000 to 2004. A total number of 7610 emergency patients visited the department during the five year period. The median (25%, 75%) of age was 32 (22, 56). Patients aged 65 years and over accounted for 16% of all attendances. All the patients were classified into 6 groups according to the diagnosis, (1) Respiratory, (2) Circulatory, (3) Central nervous system, (4) Abdominal, (5) Trauma, and (6) Others. The median age in each group was (1) 27 (15, 49), (2) 66 (53, 76), (3) 51 (27, 67), (4) 33 (22, 56), and (5) 26 (20, 46), respectively. There was a statistically significant difference observed, reciprocally except between (1) and (5) (P < 0.05). The patients showed statistically significant difference in the annual transition of the disease (P < 0.0001). In the elderly, the annual transition of the disease showed statistically significant decreases in Circulatory (P = 0.0015) and in Central nervous (P < 0.0001), and an increase in Abdominal (P < 0.0001), respectively. Death rate at the outpatient clinic in the elderly showed much higher than in the younger (P < 0.0001). Admission rate was also much higher in the elderly than in the younger (P < 0.0001). Elderly emergency patients have both internal and external intrinsic factors. They have to be treated carefully since their condition easily deteriorates. Provisions for the problems surrounding the elderly should be made as a nationwide effort.

Run down of GABAergic depolarization during metabolic inhibition of rat hippocampal CA1 neurons.

We investigated the effects of metabolic inhibition on both the shift in the equilibrium potential for Cl(-) (E(Cl)) and the run down of GABA(A) receptor responses, using nystatin- and gramicidin-perforated patch-clamp recordings from rat hippocampal CA1 neurons. Metabolic inhibition with NaCN decreased outward GABAergic currents while increasing inward GABAergic currents. E(Cl) showed a positive shift almost immediately after metabolic poisoning. This shift always occurred prior to GABA receptor run down, which was observed as decreases in whole cell conductance during application of a GABA(A) receptor agonist. The results indicate that GABAergic responses tend to become depolarizing during metabolic inhibition and the run down of the GABAergic response may therefore be neuroprotective against excitotoxicity. Furthermore the results illustrate the importance of considering both changes in receptor function and current driving force, and their temporal relationship, in order to understand the physiological response of the GABAergic system during metabolic stress.

Allopregnanolone enhancement of GABAergic transmission in rat medial preoptic area neurons.

Gamma-aminobutyric acid (GABA)-mediated transmission in the medial preoptic area (MPOA) of the hypothalamus plays an important role in functions such as sex steroid hormone dynamics and control of body temperature. The action of allopregnanolone, the primary metabolite of progesterone, on GABAergic transmission was investigated by employing patch clamp whole cell recording on acutely dissociated rat MPOA neurons with the functional connection of presynaptic terminals. Allopregnanolone enhanced spontaneous GABA release on the MPOA neurons and induced prolonged decay of miniature GABAergic-inhibitory postsynaptic currents (mIPSCs). The facilitation of GABA release from the presynaptic terminals by allopregnanolone disappeared in Ca2+-free extracellular solution. The presynaptic action of this neurosteroid was also blocked by bumetanide, a blocker of cation-Cl- cotransporters, and by removal of extracellular Na+. The results suggest that allopregnanolone enhances GABAergic transmission at the MPOA neurons by pre- and postsynaptic mechanisms. The enhancement of GABA release by allopregnanolone might require a high Cl- concentration in the presynaptic terminal maintained by Na+-dependent, bumetanide-sensitive mechanisms (e.g., Na+-K+-Cl- cotransporter) and might be mediated by Ca2+ influx into presynaptic terminal.