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.

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.

Incorporation and controlled release of silyl ether prodrugs from PRINT nanoparticles.

Asymmetric bifunctional silyl ether (ABS) prodrugs of chemotherapeutics were synthesized and incorporated within 200 nm × 200 nm particles. ABS prodrugs of gemcitabine were selected as model compounds because of the difficulty to encapsulate a water-soluble drug within a hydrogel. The resulting drug delivery systems were degraded under acidic conditions and were found to release only the parent or active drug. Furthermore, changing the steric bulk of the alkyl substituents on the silicon atom could regulate the rate of drug release and, therefore, the intracellular toxicity of the gemcitabine-loaded particles. This yielded a family of novel nanoparticles that could be tuned to release drug over the course of hours, days, or months.

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.

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.

A case of gastrointestinal histoplasmosis with esophageal involvement.

Histoplasmosis is a common infection endemic to the Ohio and Mississippi River Valleys caused by the inhalation of Histoplasma capsulatum spores from contaminated soil. Most infections are asymptomatic; however, patients with impaired cellular immunity (HIV infection, hematologic malignancy, solid organ transplant, hematopoietic stem cell transplant or TNF-⍺ inhibitor use) are at risk for disseminated disease. Disseminated histoplasmosis commonly affects the lungs, liver, spleen, bone marrow and gastrointestinal tract. Esophageal involvement is rare and usually due to extrinsic compression from affected mediastinal/hilar lymph nodes. Herein, we report a case of disseminated histoplasmosis in an AIDs patient involving the esophagus, without evidence of mediastinal involvement.

Efficacy of Cangrelor as Bridging Therapy Post PCI.

BACKGROUND: Dual antiplatelet therapy (DAPT) remains the cornerstone management for the prevention of acute stent thrombosis after percutaneous intervention (PCI). Situations mandating early interruption of DAPT carry a high risk of ischemic complications. Perioperative bridge therapy using Cangrelor, an intravenous P2Y2 inhibitor, may offer a potential solution. Unfortunately, evidence for its use in non-cardiac procedures is limited. METHODS: Our protocol demonstrates successful off-label use of IV Cangrelor bridge therapy in a non-cardiac surgery patient. We describe a case of a 77-year old male; triple therapy with Aspirin, Apixaban, and Ticagrelor for recent drug-eluting stent placement required immediate surgical resection of stage I colonic adenocarcinoma. RESULTS: Cangrelor bridge therapy was utilized both preoperatively and postoperatively without ischemic or bleeding complications. The patient tolerated exploratory laparoscopic colectomy with minimal bleeding and good post-op recovery. CONCLUSION: Minimizing the interruption of DAPT therapy in high-risk patients is achievable. However, careful planning with a team-based approach involving surgeons, cardiologists and pharmacists, along with close clinical follow-up and vigilant management of anti-platelet therapy is recommended.

Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10.

OBJECTIVE: There are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, into a readily applicable immunohistochemistry (IHC) panel. METHODS: For seven of the genes in the gene expression profile (GEP) for which suitable commercial antibodies were available, we semiquantitatively assessed the IHC expression and prognostic significance for 173 patients treated at the Saint John Regional Hospital (SJRH). Cut-offs for high and low expression were defined for each marker and applied to IHC scores from 291 of the 482 patients in JBR.10, including patients on both the adjuvant chemotherapy and observation arms. The prognostic and predictive value of these markers on overall survival (OS) or recurrence-free survival (RFS) was assessed by Cox regression models. RESULTS: In the SJRH cohort, in 62 patients with resected stage II-III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with Zhu's GEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS, HR=0.14; p<0.0001) and high STMN2 (RFS, HR=2.501; p=0.0197) were adverse prognostic factors. Low ATP1B1 and low TRIM14 expression trended toward worse OS and RFS. Validation of these markers with JBR.10 patients failed to show prognostic significance either individually or in combined risk classifications. Additionally, the interaction between these markers and chemotherapy treatment in predicting OS (FOSL2, p=0.52; STMN2 p=0.14; ATP1B1, p=0.33; TRIM14, p=0.81) or RFS (FOSL2, p=0.63; STMN2, p=0.12; ATP1B1, p=0.66; TRIM14, p=0.57) did not reach significance, individually or in combination panels. CONCLUSIONS: Zhu's GEP could not be translated into an IHC panel predictive of benefit from adjuvant chemotherapy. Future predictive biomarker analysis in the adjuvant NSCLC setting may need to focus on novel therapies.

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.