Association of blood pressure with neurologic outcome at hospital discharge after pediatric cardiac arrest resuscitation.

BACKGROUND: Poor outcomes are associated with post cardiac arrest blood pressures <5th percentile for age. We aimed to study the relationship of mean arterial pressure (MAP) with favorable neurologic outcome following cardiac arrest and return of spontaneous circulation (ROSC). METHODS: This retrospective, multi-center, observational study analyzed data from the Pediatric Resuscitation Quality Collaborative (pediRES-Q). Children (<18 years) who achieved ROSC following index in-hospital or out-of-hospital cardiac arrest and survived ≥6 hours were included. Lowest documented MAP within the first 6 hours of ROSC was percentile adjusted for age and categorized into six groups - Group I: <5th, II: 5-24th, III: 25-49th, IV: 50-74th, V: 75-94th; and VI: 95-100th percentile. Primary outcome was favorable neurologic status at hospital discharge, defined as PCPC score 1, 2, or no change from pre-arrest baseline. Multivariable logistic regression was performed to analyze the association of MAP group with favorable outcome, controlling for illness category (surgical-cardiac), initial rhythm (shockable), arrest time (weekend or overnight), age, CPR duration, and clustering by site. RESULTS: 787 patients were included: median [Q1,Q3] age 17.9 [4.8,90.6] months; male 58%; OHCA 21%; shockable rhythm 13%; CPR duration 7 [3,16] min; favorable neurologic outcome 54%. Median lowest documented MAP percentile for the favorable outcome group was 13 [3,43] versus 8 [1,37] for the unfavorable group. The distribution of blood pressures by MAP group was I: 37%, II: 28%, III: 13%, IV: 11%, V: 7%, and VI: 4%. Compared with patients in Group I (<5%ile), Groups II, III, and IV had higher odds of favorable outcome (aOR, 1.84 [95% CI, 1.24, 2.73]; 2.20 [95% CI, 1.32, 3.68]; 1.90 [95% CI, 1.12, 3.25]). There was no association between Groups V or VI and favorable outcome (aOR, 1.44 [95% CI, 0.75, 2.80]; 1.11 [95% CI, 0.47, 2.59]). CONCLUSION: In the first 6-hours post-ROSC, a lowest documented MAP between the 5th-74th percentile for age was associated with favorable neurologic outcome compared to MAP <5th percentile for age.

[Endoscopically non-removable stones of the common bile duct]. / Endoskopicheski ne udalimye kamni obshchego zhelchnogo protoka: puti resheniya problemy.

OBJECTIVE: To evaluate the effectiveness of long-term biliary stenting in the treatment of endoscopically intractable common bile duct stones. MATERIAL AND METHODS: The study enrolled 247 patients with endoscopically non-removable bile duct calculi («difficult¼ choledocholithiasis) divided into two comparable groups. The main group included 129 patients who underwent biliary stenting with original stents with a nanocarbon inert coating (RF patent No. 84226), including those with inclusion of silver nanoclusters (RF patent No. 129397). The control group included 118 patients who underwent all methods of surgical treatment of choledocholithiasis, while biliary stents with original nanocarbon silver-containing inert coating were excluded. The vast majority of patients were women of advanced age (mean 66.8±4.7 and 66.3±5.6, max 89 and 90, min 32 and 37 years, respectively). RESULTS: In the control group, all patients underwent endoscopic transpapillary interventions as soon as possible. We could not extract common bile duct stones via endoscopic approach in 56.8% of cases. These patients underwent open or laparoscopic choledocholithotomy with lithoextraction. Complications occurred in 28.5% of cases. Mortality rate was 4.2%. Standard stenting of common bile duct was performed in 28.8% of cases. At the same time, stent dysfunction followed by relapse of obstructive jaundice occurred in 27.1% of patients within 3-3.5 months. Of these, 16 patients (13.5%) underwent stent removal and lithoextraction. Re-stenting was performed in 18 patients (15.3%). Moreover, shock wave lithotripsy with subsequent removal of common bile duct calculi was performed in 8 (6.8%) of these patients the next day. In the main group, original biliary plastic stents with nanocarbon silver-containing inert coating were implanted in all patients. Under permanent therapy with ursodeoxycholic acid drugs, we observed significant shrinkage of calculi to 11.8±1.8 mm and decrease in their density. This made it possible to carry out successful extraction of calculi in 81 patients (62.8%) after 6±0.3 months. Shock wave lithotripsy was performed in 36 (27.9%) cases. This procedure was successful and allowed final lithoextraction in 28 patients (21.7%). Re-stenting was performed in 15 (11.6%) cases, laparotomy - in 5 (3.9%) patients. Mortality rate was 0.78%. CONCLUSION: Our data allow us to discuss high efficiency of long-term bile duct stenting with plastic stents with nanocarbon silver-containing inert coating in complex treatment of choledocholithiasis. This approach ensures acceptable incidence of undesirable complications and mortality. This situation undoubtedly dictates the need for further larger prospective studies.

Creation and annihilation of topological meron pairs in in-plane magnetized films.

Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in chiral magnet Co8Zn9Mn3 raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction.

Hematological adverse effects and pharmacokinetics of ribavirin in pigs following intramuscular administration.

Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double-oil emulsion (RBV-DOE) and gel (RBV-Gel), which were injected into the pigs as single-dose IM injections. After injection of RBV, all of the pigs were monitored. The collected serum and whole blood samples were analyzed by liquid chromatography-tandem mass spectrometry and complete blood count analysis, respectively. All of the ribavirin-treated pigs showed significant decreases in body weight compared to the control groups. Severe clinical signs including dyspnea, anorexia, weakness, and depression were present in ribavirin-treated pigs until 5 days postinjection (dpi). The ribavirin-treated groups showed significant decrease in the number of red blood cells and hemoglobin concentration until 8 dpi. The mean half-life of the RBV-DOE and RBV-Gel was 27.949 ± 2.783 h and 37.374 ± 3.502 h, respectively. The mean peak serum concentration (Cmax ) and area under the serum concentration-time curve from time zero to infinity (AUCinf ) of RBV-DOE were 8340.000 ± 2562.577 ng/mL and 16 0095.430 ± 61 253.400 h·ng/mL, respectively. The Cmax and AUCinf of RBV-Gel were 15 300.000 ± 3764.306 ng/mL and 207526.260 ± 63656.390 h·ng/mL, respectively. The results of this study provided the index of side effect and pharmacokinetics of ribavirin in pigs, which should be considered before clinical application.

Calpain proteolysis of alpha II-spectrin in the normal adult human brain.

The proteolysis of alphaII-spectrin by calpain may be physiologically involved with synaptic remodeling, long-term potentiation, and memory formation. Calpain activation may also mediate neuronal apoptosis, responses to hypoxic insult, and excitotoxic injury. Surprisingly little is known of the activity of these calpain-mediated processes in the adult human brain. Using an antibody that specifically recognizes calpain-cleaved alphaII-spectrin, we have mapped the topographic distribution of the major alphaII-spectrin break-down product (alphaII-bdp1) in six adult brains examined post-mortem. All brains were from patients without evident neurological disease. Focally positive alphaII-bdp1 was consistently detected in the neuropil of the cortical gray matter, in occasional pyramidal neurons, and in rare reactive astrocytes in the cerebral cortex and hippocampus. Cerebellar Purkinje cells were more frequently, and more intensely, immunopositive. In all fields, staining was most intense in the soma and dendrites of neurons. There was no correlation of the frequency of positive cells with the postmortem interval or clinical condition. While these findings do not rigorously exclude contributions from postmortem calpain activation, they do suggest that a low-level of calpain processing of alphaII-spectrin is likely to be a constitutive process in the adult human brain.

Design and synthesis of anticonvulsive agents as gamma-vinyl GABA-based potential dual acting prodrugs and their biological activities.

For the development of new anticonvulsive agents, gamma-vinyl GABA (vigabatrin) and GABA mimetics derivatives were covalently coupled as potential dual acting prodrugs and evaluated for their anticonvulsive activities. Among the prepared compounds, 11 showed the most potent anticonvulsive activity, a shorter onset time and a broader spectrum compared to vigabatrin.

Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity.

Asiatic acid, a triterpene of Centella asiatica (L.) Urban (Umbelliferae), has been patented as a treatment for dementia and an enhancer of cognition by the Hoechst Aktiengesellschaft (EP 0 383 171 A2). We modified the chemical structure of asiatic acid and obtained 36 derivatives of asiatic acid in an attempt to prepare neuroprotective compounds that were more efficacious than asiatic acid itself. The neuroprotective activities of these derivatives were evaluated using primary cultures of rat cortical neurons insulted with the neurotoxin, glutamate, as an in vitro screening system. Among the semi-synthesized derivatives, three derivatives significantly mitigated the neurotoxicity induced by glutamate in this screening system. The neuroprotective activities of these 3 derivatives appeared to be more powerful than that of asiatic acid itself. These 3 derivatives significantly attenuated decreases in the levels of glutathione, glutathione peroxidase and other enzymes, which participate in the cellular defense mechanisms blunting oxidative stress. Furthermore, they significantly reduced the overproduction of NO induced by glutamate. These results showed that these derivatives of asiatic acid exerted significant neuroprotective effects on cultured cortical cells by their potentiation of the cellular oxidative defense mechanism. Therefore, these agents may prove to be efficacious in protecting neurons from the oxidative damage caused by exposure to excess glutamate.