The Use of Pleural Adenosine Deaminase in the Early Diagnosis and Treatment of Spinal Tuberculosis.

Spinal tuberculosis (TB) is associated with serious neurologic morbidity. It commonly presents as back pain, with or without systemic symptoms. Magnetic resonance imaging (MRI) is the most sensitive and specific imaging modality for spinal TB. The diagnosis of spinal TB is made with tissue biopsy and acid-fast bacilli (AFB) culture; however, tissue AFB smear and tissue TB deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) can influence early clinical decision making. Ancillary tests such as the purified protein derivative (PPD) skin test, QuantiFERON®-TB Gold (QFT) or pleural adenosine deaminase (ADA) can be used in conjunction with radiology and clinical findings to initiate treatment while AFB tissue cultures are pending. Spinal TB responds well to early medical management and surgery is reserved for cases with neurologic complications.

Haemophilus parainfluenzae Pyogenic Liver Abscess Associated With Cholangiocarcinoma.

Haemophilus parainfluenzae (H. parainfluenzae) is a commensal organism of the gastrointestinal tract. It rarely causes hepatobiliary infections; however, in the presence of underlying inflammation, immunosuppression, or malignancy, it can cause hepatobiliary infection via an ascending route. Herein, we report a case of pyogenic liver abscess secondary to H. parainfluenzae associated with cholangiocarcinoma, which was treated with ceftriaxone and metronidazole.

Dysphagia after Stroke: An Unmet Antibiotic Stewardship Opportunity.

The goal of antibiotic stewardship is to improve antibiotic use, often by reducing unnecessary treatment. Bedside dysphagia screening tools help identify patients at high risk of aspiration following stroke. Presence of dysphagia does not indicate a need for antibiotic treatment. Therefore, this retrospective, cohort study was developed to evaluate the association of dysphagia and antibiotic prescribing following stroke. There were 117 patients included. Patients were placed into 2 cohorts based on the results of the dysphagia screening, with 55 patients positive for dysphagia and 62 patients negative for dysphagia. Patients with dysphagia tended to be older, had higher National Institutes of Health stroke scores, and lower renal function. Patients with dysphagia were prescribed more empiric antibiotics than those without dysphagia (18.2% vs. 3.2%, p = 0.01). This resulted in 53 antibiotic days of therapy in the dysphagia cohort compared to 19 antibiotic days of therapy in the no dysphagia cohort (p = 0.1). No patients later developed pneumonia and only one patient was started antibiotics after 48 h. Two cases of Clostridioides difficile were reported. Both patients were in the dysphagia cohort and received antibiotics. Multivariable logistic regression demonstrated that positive chest x-ray findings and failed dysphagia screen were independent conditions associated with initiating antibiotics. These findings indicate that antibiotic use was higher in patients following stroke with a positive dysphagia screen. Close monitoring of stroke patients, particularly when positive for dysphagia, might be an under-recognized antibiotic stewardship opportunity.

Particle replication in nonwetting templates nanoparticles with tumor selective alkyl silyl ether docetaxel prodrug reduces toxicity.

Delivery systems designed to have triggered release after passively targeting the tumor may improve small molecule chemotherapeutic delivery. Particle replication in nonwetting templates was used to prepare nanoparticles to passively target solid tumors in an A549 subcutaneous xenograft model. An acid labile prodrug was delivered to minimize systemic free docetaxel concentrations and improve tolerability without compromising efficacy.

Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy.

Nanoparticle (NP) drug loading is one of the key defining characteristics of an NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT(®)), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel.

Synthesis, structure, and reactivity of iridium(III) complexes containing a 4,6-dimethyl-1,3-benzenediphenylimine pincer ligand.

A nonheterocyclic bis(imino)aryl ligand with blocking methyl substituents, 4,6-dimethyl-1,3-benzenediphenylimine (NCHN), has been synthesized. Metalation via oxidative addition proceeds under mild conditions with the Ir(I) reagent [Ir(CH(2)═CH(2))(2)(Cl)](2) to produce the Ir(III) product (NCN)Ir(CH(2)CH(3))(Cl). Neutral nucleophiles such as water or triphenylphosphine add readily to the vacant sixth coordination site. Protonation of the ethyl group results in loss of ethane and formation of a dicationic chloride-bridged (NCN)Ir dimer. Alternatively, the chloride ligand can be abstracted from (NCN)Ir(CH(2)CH(3))(Cl) to provide access to various neutral and cationic species, including (NCN)Ir(CH(2)CH(3))(OAc) (OAc = acetate), [(NCN)Ir(CH(2)CH(3))(bpy)][BF(4)] (bpy = 4,4'-bipyridine), [(NCN)Ir(CH(2)CH(3))(NCCH(3))(2)][BF(4)], and [(NCN)Ir(CH(2)CH(3))(OH(2))(2)][BF(4)], which is water soluble.