Prevention of contrast‐induced acute kidney injury in patients with stable chronic renal disease undergoing elective percutaneous coronary and peripheral interventions: Randomized comparison of two preventive strategies

Objective : We compared use of intravenous (IV) normal saline (NS) to sodium bicarbonate (NaHCO₃) with or without oral N‐acetylcysteine (NAC) for prevention of contrast‐induced acute kidney injury (CI‐AKI). Background : CI‐AKI is associated with significant adverse clinical events. Use of NAC has produced variable results. Recently, intravenous hydration with NaHCO₃ for CI‐AKI prophylaxis has been adopted as standard treatment for patients with stable chronic renal disease undergoing catheterization procedures. Methods : We prospectively enrolled 320 patients with baseline renal insufficiency scheduled to undergo catheterization. Patients were randomly assigned to receive either IV NS ± NAC (n = 161) or IV dextrose 5% in water containing 154 mEq/l of NaHCO₃ ± NAC (n = 159). IV NS was administered at 1 ml/kg body weight for 12 hr preprocedure and 12 more hr postprocedure. IV NaHCO₃ was administered at 3 ml/kg body weight for 1 hr preprocedure followed by 1 ml/kg body weight postprocedure. A 1,200 mg oral dose of NAC was given 2–12 hr preprocedure and 6–12 hr postprocedure in 50% of patients in each study arm. CI‐AKI was defined as an increase of >0.5 mg/dl or >25% above baseline creatinine. Results : Overall incidence of CI‐AKI was 10.3%. There was no significant difference in incidence among the two groups (NS ± NAC 11.8% vs. NaHCO₃ ± NAC 8.8%, p = ns). Incidence of CI‐AKI increased with increasing age (p = 0.001), contrast agent use >3 ml/kg body weight (p = 0.038) and diuretic use (p = 0.005). Conclusion : Incidence of CI‐AKI was no different in the NaHCO₃ group compared to NS group, and NAC did not reduce CI‐AKI in the two study arms. © 2011 Wiley Periodicals, Inc.     

Initiation of osteoporosis assessment in the fracture clinic results in improved osteoporosis management: a randomised controlled trial

Summary

Osteoporosis management post fragility fracture has traditionally been deficient with up to 60–90 % of patients remaining untreated for osteoporosis in some studies. Efforts have been made to address this deficiency with some successes reported.

Introduction

The aim of this study was to assess the efficacy of two different models of screening for osteoporosis in a community fracture clinic setting.

Methods

A prospective randomised clinical trial was conducted to assess the DXA scan and treatment rates in patients with fragility fractures when assessment for osteoporosis had been initiated in the fracture clinic compared with the “usual care” of assessment initiation by the participant’s general practitioner.

Results

Sixty-six patients were enrolled in the study. Thirty-three patients each were in the control and intervention groups. The assessment rate (DXA scan rate) was significantly better in the intervention group where participants were referred for assessment from fracture clinic compared to the control group where participants were referred for assessment by their general practitioner (68 vs 36 %, respectively; p?<?0.05). For patients who were assessed for osteoporosis, treatment rates were similar in both the control and intervention groups (100 vs 88 %, p?>?0.05).

Conclusion

This study demonstrates that screening for osteoporosis initiated in fracture clinic results in improved osteoporosis management compared to screening initiated in primary care. Orthopaedic surgeons and other specialists need to be more active in managing osteoporosis in patients who present with fragility fractures and should at the very least initiate assessment in the fracture clinic setting.     

Association study of the vesicular monoamine transporter gene SLC18A2 with tardive dyskinesia

Tardive dyskinesia (TD) is an involuntary movement disorder that can occur in up to 25% of patients receiving long-term first-generation antipsychotic treatment. Its etiology is unclear, but family studies suggest that genetic factors play an important role in contributing to risk for TD. The vesicular monoamine transporter 2 (VMAT2) is an interesting candidate for genetic studies of TD because it regulates the release of neurotransmitters implicated in TD, including dopamine, serotonin, and GABA. VMAT2 is also a target of tetrabenazine, a drug used in the treatment of hyperkinetic movement disorders, including TD. We examined nine single-nucleotide polymorphisms (SNPs) in the SLC18A2 gene that encodes VMAT2 for association with TD in our sample of chronic schizophrenia patients (n = 217). We found a number of SNPs to be nominally associated with TD occurrence and the Abnormal Involuntary Movement Scale (AIMS), including the rs2015586 marker which was previously found associated with TD in the CATIE sample ( Tsai et al., 2010), as well as the rs363224 marker, with the low-expression AA genotype appearing to be protective against TD (p = 0.005). We further found the rs363224 marker to interact with the putative functional D2 receptor rs6277 (C957T) polymorphism (p = 0.001), supporting the dopamine hypothesis of TD. Pending further replication, VMAT2 may be considered a therapeutic target for the treatment and/or prevention of TD.     

The Pregnancy,Arsenic, and Immune Response (PAIR) Study in rural northern Bangladesh

Background

Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the foetus, and maternal and infant acute morbidity.

Objectives

The Pregnancy, Arsenic, and Immune Response (PAIR) Study was designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal and newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy.

Population

The PAIR Study recruited pregnant women across a large rural study area in Gaibandha District, northern Bangladesh, 2018–2019.

Design

Prospective, longitudinal pregnancy and birth cohort.

Methods

We conducted home visits to enrol pregnant women in the late first or early second trimester (11–17 weeks of gestational age). Women received a quadrivalent seasonal inactivated influenza vaccine at enrolment. Follow-up included up to 13 visits between enrolment and 3 months postpartum. Arsenic was measured in drinking water and maternal urine. Micronutrient deficiencies were assessed using plasma biomarkers. Vaccine-specific antibody titres were measured in maternal and infant serum. Weekly telephone surveillance ascertained acute morbidity symptoms in women and infants.

Preliminary Results

We enrolled 784 pregnant women between October 2018 and March 2019. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visits to 3 months postpartum. Arsenic was detected (≥0.02 μg/L) in 99.7% of water specimens collected from participants at enrolment. The medians (interquartile ranges) of water and urinary arsenic at enrolment were 5.1 (0.5, 25.1) μg/L and 33.1 (19.6, 56.5) μg/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's ⍴ = 0.72) among women with water arsenic ≥ median but weakly correlated (⍴ = 0.17) among women with water arsenic < median.

Conclusions

The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants. Registration : NCT03930017.     

Subthalamic deep brain stimulation affects heading perception in Parkinson’s disease

Journal of Neurology - Parkinson’s disease (PD) presents with visuospatial impairment and falls. It is critical to understand how subthalamic deep brain stimulation (STN DBS) modulates...     

Controlled Release in Transdermal Pressure Sensitive Adhesives using Organosilicate Nanocomposites

Polydimethyl siloxane (PDMS) based pressure sensitive adhesives (PSA) incorporating organo-clays at different loadings were fabricated via solution casting. Partially exfoliated nanocomposites were obtained for the hydroxyl terminated PDMS in ethyl acetate solvent as determined by X-ray diffraction and atomic force microscopy. Drug release studies showed that the initial burst release was substantially reduced and the drug release could be controlled by the addition of organo-clay. Shear strength and shear adhesion failure temperature (SAFT) measurements indicated substantial improvement in adhesive properties of the PSA nanocomposite adhesives. Shear strength showed more than 200% improvement at the lower clay loadings and the SAFT increased by about 21% due to the reinforcement provided by the nano-dispersed clay platelets. It was found that by optimizing the level of the organosilicate additive to the polymer matrix, superior control over drug release kinetics and simultaneous improvements in adhesive properties could be attained for a transdermal PSA formulation.     

Implications of Off‐Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach

Study Objective

Serotonergic adverse drug events (ADEs) are caused by enhanced intrasynaptic concentrations of 5‐hydroxytryptamine (5‐HT). No systematic process currently exists for evaluating cumulative 5‐HT and off‐target toxicity of serotonergic drugs. The primary study aim was to create a Serotonergic Expanded Bioactivity Matrix (SEBM) by using a molecular bioinformatics, polypharmacologic approach for assessment of the participation of individual 5‐HT drugs in serotonin syndrome (SS) reports.

Data Sources

Publicly available databases including the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), ChEMBL, DrugBank, PubChem, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were queried for computational and pharmacologic data.

Design

An in‐house bioinformatics TargetSearch program ( http://dxulab.org/software ) was used to characterize 71 serotonergic drugs interacting at 13 serotonin receptor subtypes and serotonin reuptake transporter protein (SERT). In addition, off‐target interactions at norepinephrine transporter (NET), monoamine oxidase (MAO), and muscarinic receptors were included to define seven polypharmacological drug cohorts. Serotonin syndrome reports for each serotonergic drug were extracted from FAERS by using the Sternbach and Hunter criteria.

Measurements and Main Results

A proportional reporting adverse drug reaction (ADR) ratio (PRR) was calculated from each drug's total ADEs and SS case reports and aggregated by drug bioactivity cohorts. Triple‐receptor interactions had a disproportionately higher number of SS cases using both the Hunter criteria (mean PRR 1.72, 95% CI 1.05–2.39) and Sternbach (mean PRR 1.54, 95% CI 1.29–1.79). 5‐Hydroxytryptamine agonists were associated with a significantly lower proportion of SS cases using the Hunter and Sternbach criteria, respectively (mean PRR 0.49, 95% CI 0.17–0.81 and mean PRR 0.49, 95% CI 0.15–0.83). Drugs with disproportionately higher participation in SS vary considerably between the two diagnostic criteria.

Conclusion

The SEBM model suggests a possible polypharmacological role in SS. Although further research is needed, off‐target receptor activity may help explain differences in severity of toxicity and clinical presentation.     

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl₄, FeCl₂), whereas Na₂SeO₃ supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.     

Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group

OBJECTIVE: To provide a uniform platform from which to study acute liver failure, the U.S. Acute Liver Failure Study Group has sought to standardize the management of patients with acute liver failure within participating centers. METHODS: In areas where consensus could not be reached because of divergent practices and a paucity of studies in acute liver failure patients, additional information was gleaned from the intensive care literature and literature on the management of intracranial hypertension in non-acute liver failure patients. Experts in diverse fields were included in the development of a standard study-wide management protocol. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure monitoring is recommended in patients with advanced hepatic encephalopathy who are awaiting orthotopic liver transplantation. At an intracranial pressure of > or =25 mm Hg, osmotic therapy should be instituted with intravenous mannitol boluses. Patients with acute liver failure should be maintained in a mildly hyperosmotic state to minimize cerebral edema. Accordingly, serum sodium should be maintained at least within high normal limits, but hypertonic saline administered to 145-155 mmol/L may be considered in patients with intracranial hypertension refractory to mannitol. Data are insufficient to recommend further therapy in patients who fail osmotherapy, although the induction of moderate hypothermia appears to be promising as a bridge to orthotopic liver transplantation. Empirical broad-spectrum antibiotics should be administered to any patient with acute liver failure who develops signs of the systemic inflammatory response syndrome, or unexplained progression to higher grades of encephalopathy. Other recommendations encompassing specific hematologic, renal, pulmonary, and endocrine complications of acute liver failure patients are provided, including their management during and after orthotopic liver transplantation. CONCLUSIONS: The present consensus details the intensive care management of patients with acute liver failure. Such guidelines may be useful not only for the management of individual patients with acute liver failure, but also to improve the uniformity of practices across academic centers for the purpose of collaborative studies.     

Imaging of pediatric liver tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%–2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy.