Saint Luke's East Hospital

Tacrolimus, a potent immunosuppressive agent widely used in solid organ transplantation, has been associated with numerous harmful side effects. We report an interesting case of a patient who is status post liver transplantation and who has been maintained on tacrolimus for the past 10 years. She presented in the hospital with a ST-segment elevation myocardial infarction (STEMI), with normal coronary angiography. The patient was found to have a markedly elevated tacrolimus level. After decreasing the dose of tacrolimus and starting isosorbide mononitrate, the patient's symptoms resolved, and the patient had no recurrence of symptoms.

The purpose of this technologic analysis was to review use of ionic silver as a component of topical wound therapy products. Published literature from a variety of fields related to ionic silver and its use in topical wound therapy products was reviewed and a summary of common commercially available wound care products containing ionic silver was generated, along with general recommendations for use. Safety information from both manufacturer guidelines and the Manufacturer and User Facility Device Experience (MAUDE) database is summarized. Various formulations of ionic silver products are used for topical treatment of wounds. Antimicrobial activity varies according to the specific silver formulation and type of microorganisms in the wound bed. In vitro evidence suggests that some bacterial strains may be developing resistance to ionic silver. Improved knowledge of the benefits and safety precautions associated with topical silver preparations can guide its application to topical therapy for wound healing.

Penile squamous cell carcinoma (PSCC) is rare with limited treatment options. We report the first whole-exome sequencing (WES) analysis and compare the molecular landscape of PSCC with other squamous cell carcinomas (SCC), with the goal to identify common novel targets. PSCC and matched normal penile tissues from 34 prospectively followed patients, underwent genomic WES and human papilloma virus testing. We performed tumor mutation signature estimation by two methods, first to identify APOBEC-related mutation enrichments and second to classify PSCC-enriched mutational patterns based on their association with the Catalogue of Somatic Mutations in Cancer mutation signatures. We performed an extensive genomic comparison between our PSCC cohort and other SCCs in The Cancer Genome Atlas studies. We identified that most PSCC samples showed enrichment for Notch pathway (n = 24, 70.6%) alterations, comparable with head and neck squamous cell carcinoma (HNSC). PSCC mutation signatures are most comparable with HNSC signatures. PSCC samples showed an enrichment of two distinct mutational signatures, the first, associated with oncogenic activity of AID/APOBEC, and the second, associated with defective DNA mismatch repair and microsatellite instability. MP1 enrichment was positively correlated with increased tumor mutation burden (TMB; CC, 0.71; P < 0.0001) and correlated with significantly worse survival in comparison with those with the MP2 subset [HR, 10.2 (1.13-92.9); P = 0.039]. We show that a subset of PSCC (38%), with enrichment of APOBEC-related mutation signature, had significantly higher TMB and worse overall survival in comparison with non-APOBEC-enriched subset [HR, 2.41 (1.11-6.77); P = 0.042]. This study identified novel druggable targets and similarities in mutational signatures between PSCC and HNSC with potential clinical implications.See related commentary by McGregor and Sonpavde, p. 2375.

To describe a process to identify metrics that represent the impact of inpatient pharmacy services on patient outcomes across a health system. The authors describe a systematic process of identifying inpatient clinical outcome measures that could represent pharmacists' impact on patient outcomes and eventually be displayed in a dashboard within the electronic medical record (EMR). A list was generated through literature review, assessment of practices at other sites, evaluation of current pharmacy services, and collaboration with the quality department and System Pharmacy Clinical User Group. The project team narrowed the list through assessment against standardized criteria. An assessment tool was designed and distributed to stakeholders to prioritize clinical outcome measures for inclusion on the dashboard. The clinical outcome measures were transformed into metrics by determining measurement criteria, inclusion and exclusion parameters, and review time frame. After validation, the metrics are planned to be displayed on an inpatient pharmacy EMR dashboard. Exemption from institutional review board review was granted for this project. A systematic process was developed and used to identify inpatient clinical outcome metrics.