Biotin functionalization of 8-hydroxyquinoline anticancer organometallics: low toxicity but potent activity.

[M(arene)(HQ)Cl] complexes (M = Ru/Os/Rh/Ir; HQ = 8-hydroxyquinoline) have shown promise as anticancer agents. To assess the effect of conjugating biotin (vitamin B7) to such compounds and improve their tumor-targeting ability through interaction with the sodium-dependent multivitamin transporter (SMVT), the chlorido co-ligand was exchanged with biotinylated 6-aminoindazole. The complexes were characterized by NMR spectroscopy and mass spectrometry, and purity was determined by elemental analysis.

Guideline concordance of electronic health record order sets for hospital-based treatment of alcohol withdrawal syndrome.

Background: Treatment of alcohol withdrawal syndrome (AWS) in hospitals is inconsistent. Electronic health record (EHR) order sets protocolize care.

Objective: We examined variation in AWS order sets across hospital organizations and their concordance with AWS guidelines.

Sepsis Order Set Use Associated With Increased Care Value.

Background: Sepsis is common and expensive, and evidence suggests that sepsis order sets may help to improve care. Very incomplete evidence exists regarding the effects of sepsis order sets on the value of care produced by hospitals or the societal costs of sepsis care.

Research Question: In patients hospitalized for sepsis, is the receipt a of a sepsis order set vs no order set associated with improved value of care, defined as decreased hospital mortality, decreased hospital direct variable costs, and decreased societal spending on hospitalizations?

Study Design And Methods: This retrospective cohort study included patients discharged with sepsis International Classification of Diseases, Tenth Revision, codes over 2 years from a large integrated delivery system.

Alcohol Withdrawal Severity Measures for Identifying Patients Requiring High-Intensity Care.

Objectives: Alcohol withdrawal syndrome (AWS) may progress to require high-intensity care. Approaches to identify hospitalized patients with AWS who received higher level of care have not been previously examined. This study aimed to examine the utility of Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-Ar) for alcohol scale scores and medication doses for alcohol withdrawal management in identifying patients who received high-intensity care.

Critical care for patients with substance use disorders.

Purpose Of Review: To examine the impact of substance use disorders (SUDs) on critical illness and the role of critical care providers in treating SUDs. We discuss emerging evidence supporting hospital-based addiction treatment and highlight the clinical and research innovations needed to elevate the standards of care for patients with SUDs in the intensive care unit (ICU) amidst staggering individual and public health consequences.

Recent Findings: Despite the rapid increase of SUDs in recent years, with growing implications for critical care, dedicated studies focused on ICU patients with SUDs remain scant.

Benzodiazepine Treatment and Hospital Course of Medical Inpatients With Alcohol Withdrawal Syndrome in the Veterans Health Administration.

Objective: To describe initial benzodiazepine dosing strategies and factors associated with variation in benzodiazepine dosing in a national cohort of hospitalized patients with alcohol withdrawal syndrome (AWS).

Patients And Methods: This cross-sectional study included adult patients with AWS admitted to medical services and treated with benzodiazepines at 93 Veterans Health Administration hospitals in 2013. Treatment was categorized by initial benzodiazepine dosing strategy-fixed-dose, symptom-triggered, or front-loading.

Synthetic Strategy Towards Heterodimetallic Half-Sandwich Complexes Based on a Symmetric Ditopic Ligand.

Multimetallic complexes have been shown in several examples to possess greater anticancer activity than their monometallic counterparts. The increased activity has been attributed to altered modes of action. We herein report the synthesis of a series of heterodimetallic compounds based on a ditopic ligand featuring 2-pyridylimine chelating motifs and organometallic half-sandwich moieties.

Incorporation of β-Alanine in Cu(II) ATCUN Peptide Complexes Increases ROS Levels, DNA Cleavage and Antiproliferative Activity.

Redox-active Cu(II) complexes are able to form reactive oxygen species (ROS) in the presence of oxygen and reducing agents. Recently, Faller et al. reported that ROS generation by Cu(II) ATCUN complexes is not as high as assumed for decades.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T-T continuum to advance the care of hospitalized patients who experience SAWS.

Differentiation of Primary Central Nervous System Lymphoma and High-Grade Glioma with Dynamic Susceptibility Contrast-Derived Metrics: Pilot Study.

Objective: Preoperative differentiation of lymphoma from other aggressive intracranial neoplasms is important as the surgical and adjuvant therapy may be fundamentally different between the 2 types of tumors. The purpose of this study was to assess the ability of the dynamic susceptibility contrast-derived metrics, percentage signal recovery (PSR) ratio, and relative cerebral blood volume (rCBV) to distinguish between primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG).

Methods: Twenty-six patients (15 with HGG and 11 with PCNSL) with histologically confirmed diagnoses were retrospectively analyzed.

Promoting Evidence-Based Practice in Acute Respiratory Distress Syndrome: A Systematic Review.

Unlabelled: Low tidal volume ventilation and prone positioning are recommended therapies yet underused in acute respiratory distress syndrome. We aimed to assess the role of interventions focused on implementation of low tidal volume ventilation and prone positioning in mechanically ventilated adult patients with acute respiratory distress syndrome.

Data Sources: PubMed, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials.

Should the CIWA-Ar be the standard monitoring strategy for alcohol withdrawal syndrome in the intensive care unit?

Background: The Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) is commonly used in hospitals to titrate medications for alcohol withdrawal syndrome (AWS), but may be difficult to apply to intensive care unit (ICU) patients who are too sick or otherwise unable to communicate.

Objectives: To evaluate the frequency of CIWA-Ar monitoring among ICU patients with AWS and variation in CIWA-Ar monitoring across patient demographic and clinical characteristics.

Methods: The study included all adults admitted to an ICU in 2017 after treatment for AWS in the Emergency Department of an academic hospital that standardly uses the CIWA-Ar to assess AWS severity and response to treatment.

Use of Electronic Health Record Data to Estimate the Probability of Alcohol Withdrawal Syndrome in a National Cohort of Hospitalized Veterans.

Objectives: Inpatient alcohol withdrawal syndrome (AWS) is common and early treatment improves outcomes, but no prior study has used electronic health record (EHR) data, available at admission, to predict the probability of inpatient AWS. This study estimated the probability of inpatient AWS using prior-year EHR data, hypothesizing that documented alcohol use disorder (AUD) and AWS would be strongly associated with inpatient AWS while exploring associations with other patient characteristics.

Methods: The study investigated patients hospitalized ≥24 hours on medical services in the Veterans Health Administration during 2013 using EHR data extracted from the Veterans Health Administration Corporate Data Warehouse.

Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs.

Proteomics has played an important role in elucidating the fundamental processes occuring in living cells. Translating these methods to metallodrug research ('metalloproteomics') has provided a means for molecular target identification of metal-based anticancer agents which should signifcantly advance the research field. In combination with biological assays, these techniques have enabled the mechanisms of action of metallodrugs to be linked to their interactions with molecular targets and aid understanding of their biological properties.

Potent Inhibition of Thioredoxin Reductase by the Rh Derivatives of Anticancer M(arene/Cp*)(NHC)Cl Complexes.

Metal complexes provide a versatile platform to develop novel anticancer pharmacophores, and they form stable compounds with -heterocyclic carbene (NHC) ligands, some of which have been shown to inhibit the cancer-related selenoenzyme thioredoxin reductase (TrxR). To expand a library of isostructural NHC complexes, we report here the preparation of Rh- and Ir(Cp*)(NHC)Cl (Cp* = η-pentamethylcyclopentadienyl) compounds and comparison of their properties to the Ru- and Os(cym) analogues (cym = η--cymene). Like the Ru- and Os(cym) complexes, the Rh- and Ir(Cp*) derivatives exhibit cytotoxic activity with half maximal inhibitory concentration (IC) values in the low micromolar range against a set of four human cancer cell lines.

Rare radiculopathy from an osteochondral loose body: a case report and literature review.

Lumbar radiculopathy is usually caused by nerve compression due to herniated disc material or compression by degenerative pathology such as enlarged facet joints, thickened ligamentum flavum or synovial cysts. We report the case of a 48-year-old female with L5 sciatica due to an osteochondral loose body in the foramen. This is only the third reported case of a single osteochondral loose body in the lumbar spine and the first reported case found in the foramen.

Anticancer organorhodium and -iridium complexes with low toxicity in vivo but high potency in vitro: DNA damage, reactive oxygen species formation, and haemolytic activity.

Redox-modulating anticancer drugs allow the exploitation of altered redox biology observed in many cancer cells. We discovered dinuclear RhIII(Cp*) and IrIII(Cp*) complexes that have in vitro anticancer activity superior to cisplatin and the investigational drug IT-139, while being less toxic in haemolysis and in vivo zebrafish models. The mode of action appears to be related to DNA damage and ROS-mediated stress pathways.

Hydroxyquinoline-derived anticancer organometallics: Introduction of amphiphilic PTA as an ancillary ligand increases their aqueous solubility.

Organometallic compounds based on bioactive ligand systems have shown promising antiproliferative properties. The use of 8-hydroxyquinoline and its derivatives as bioactive ligands resulted in organometallic complexes with potent anticancer activity, but they lack aqueous solubility for further development. We report here the preparation of a series of M(cym/Cp*)Cl complexes (η-p-cymene (cym): M = Ru, Os; η-pentamethylcyclopentadienyl (Cp*): M = Rh, Ir) with hydroxyquinoline-derived co-ligands and in a subsequent step the substitution of the chlorido ligands for amphiphilic 1,3,5-triaza-7-phosphatricyclo-[3.

Clinical and radiological outcomes of image guided posterior C1-C2 fixation for atlantoaxial osteoarthritis (AAOA).

Background: Atlantoaxial (C1-C2) osteoarthritis (AAOA) causes severe suboccipital pain exacerbated by lateral rotation. The pain is usually progressive and resistant to conservative therapy. Posterior fusion surgery is performed to stabilise the C1-C2 segment.